Synthesis of deoxy and methoxy analogs of octyl α-d-mannopyranosyl-(1→6)-α-d-mannopyranoside as probes for mycobacterial lipoarabinomannan biosynthesis

Article abstract of DOI:10.1016/j.carres.2007.05.001

A panel of analogs of the disaccharide α-d-Manp-(1→6)-α-d-Manp-OOctyl, a known acceptor substrate for a polyprenol monophosphomannose-dependent α-(1→6)-mannosyltransferase involved in the assembly of the α-(1→6)-linked mannan core of mycobacterial lipoara

Full text of DOI:10.1016/j.carres.2007.05.001

Carbohydrate Research 342 (2007) 1741–1772
Synthesis of deoxy and methoxy analogs of octyl
a-D-mannopyranosyl-(1!6)-a-D-mannopyranoside as
probes for mycobacterial lipoarabinomannan biosynthesis
Pui-Hang Tam and Todd L. Lowary*
Alberta Ingenuity Centre for Carbohydrate Science and Department of Chemistry, The University of Alberta,
Gunning-Lemieux Chemistry Centre, Edmonton, AB, Canada T6G 2G2
Received 11 April 2007; received in revised form 26 April 2007; accepted 1 May 2007
Available online 22 May 2007
Abstract—A panel of analogs of the disaccharide a-D-Manp-(1!6)-a-D-Manp-OOctyl, a known acceptor substrate for a polyprenol
monophosphomannose-dependent a-(1!6)-mannosyltransferase involved in the assembly of the a-(1!6)-linked mannan core of
mycobacterial lipoarabinomannan, has been synthesized. Described are synthetic routes to the target deoxy and methoxy analogs
in which one of the hydroxyl groups of the parent disaccharide has been modified. All glycosylation reactions involved the use of
octyl glycoside acceptors and thioglycoside donors using iodonium-ion activation, and the stereochemistry of the mannopyranoside
bond formed was established by measurement of the 1JC-1,H-1. Depending on the target, the key methylation or deoxygenation reac-
tions were carried out on either mono- or disaccharide substrates. This series of analogs will be useful for probing the substrate
specificity of the enzyme, in particular, its steric and hydrogen-bonding requirements.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: Cell-wall biosynthesis; Mycobacteria; Mannosyltransferase; Synthesis; Deoxy analogs; Methoxy analogs; Lipoarabinomannan
1. Introduction
gence of TB, due to the emergence of multidrug-resis-
tant M. tuberculosis strains4,5 and the advent of the
HIV/AIDS pandemic,6 has generated increasing interest
in the development of new anti-TB drugs. The mycobac-
terial cell wall is an ideal target for the action of new
classes of anti-TB agents because of its important role
in the structural integrity of the organism and its
immunomodulatory effects. In particular, the enzymes
involved in the cell-wall polysaccharide biosynthesis
represent a rich source of potential therapeutic drug
targets.
The structure of mycobacterial LAM (1, Fig. 1) con-
sists of a phosphatidyl-myo-inositol (PI) moiety, a man-
nan core and a highly branched arabinan domain at the
nonreducing end. With its lipid portion noncovalently
associated with the plasma membrane, the PI moiety
serves as the attachment point for the mannan and arab-
inan domains. The mannan core consists of a polymer of
a-(1!6)-linked D-mannopyranose residues and is fur-
ther elaborated, on approximately half of these core
Tuberculosis (TB) is a common and deadly infectious
disease caused by the human pathogen Mycobacterium
tuberculosis. The difficulty in treating TB arises from
the unusual structure of the mycobacterial cell wall,
which protects the pathogen from the host’s immunity
and serves as a formidable barrier to the passage of
antibiotics. Lipoarabinomannan (LAM) as well as its
related precursors lipomannan (LM) and phosphatidyl-
myo-inositol mannosides (PIMs) are the major lipogly-
cans found in the cell wall of mycobacteria.1,2 These
molecules have important roles in the modulation of
and interaction with the immune system, and allow these
organisms to survive in the hostile environment within
infected human host macrophages.3 The recent resur-
*
Corresponding author. Tel.: +1 780 492 1861; fax: +1 780 492
7705; e-mail: tlowary@ualberta.ca
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.05.001

1742
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
OH
O
have been identified.3,17–21 Among these is a polyprenol
HO
HO
HO
monophosphomannose-dependent a-(1!6)-mannosyl-
transferase (ManT) that is involved in the synthesis of
the linear a-(1!6)-linked mannan core.22,23 This ManT
catalyzes the transfer of mannopyranose residues from
polyprenol monophosphomannose derivatives (PPM,
2a, 2b, Fig. 2) to an a-(1!6)-linked oligomannopyrano-
side acceptor. In turn PPM 2a and 2b are synthesized
from GDP-mannose (GDP-Man, 3) by the enzyme poly-
prenol monophosphomannose synthase.24 To date, the
gene encoding for this ManT has not been identified,
nor has the protein been isolated; its activity has only
been demonstrated using a cell-free assay.23,25–28
Earlier work by Brown et al. showed that the octyl
glycosides containing two or three a-(1!6)-linked
mannopyranose residues can act as acceptor substrates
for this ManT.23 The hydrophobic nature of the octyl
agylcone allows convenient product isolation and
characterization in cell-free enzymatic assays using re-
versed-phase chromatography. Analogs of these simpli-
fied acceptors can be used for probing the substrate
specificity of the enzyme. For example, in very recent
studies,27,28 derivatives of octyl disaccharide 4 (Fig. 3)
were synthesized and screened as potential substrates
and inhibitors of this ManT. These analogs were those
in which the hydroxyl groups at the C-2 and C-6 posi-
tions of the terminal mannose residue were singly or
doubly modified by replacement with hydrogen or
fluoro, amino, and methoxy functionalities.
O
O
Arabinan
O
HO
HO
X
OH
O
O
HO
HO
Mannan Core
O
OH
HO
HO
O
O
HO
HO
Phosphatidyl-
myo-inositol
OPO3DAG
HO
O
HO
HO
O
AcylO
OH
1
Figure 1. Structure of LAM, highlighting the mannan core region;
DAG = diacylglycerol.
monosaccharides, by additional D-mannopyranose units
on O-2 in species such as M. tuberculosis, M. leprae, M.
kansasii, and M. smegmatis1,2 or at O-3 in M. chelonae.7
The arabinan domain is composed of a-(1!5)-, a-
(1!3)-, b-(1!2)-linked D-arabinofuranose residues8–10
and is substituted at its nonreducing terminus with a
range of capping motifs including D-mannopyranose
oligosaccharides, inositol phosphate groups, or 5-thio-
methyl-D-xylofuranose residues.11–16
Understanding of the complete substrate specificity of
the ManT enzyme is essential and would provide guide-
lines for the further design of potent and specific inhib-
itors. Such compounds would be useful biochemical
tools and may also have potential as lead compounds
The biosynthesis of mycobacterial LAM has been
proposed16 to involve a number of glycosyltransferases,
and over the past few years several of these enzymes
PPM
HO
HO
HO
OH
O
O
P
O
synthase
GDP-Man
O
O R
OH
O
HO
HO
HO
2
OH
O
HO
HO
HO
OH
O
O
HO
HO
ManT
OH
O
O
HO
HO
OH
O
O
HO
HO
O
P
O
O
O
O
O R
O
N
2a, R =
HO
HO
HO
OH
O
N
N
NH
NH2
O
O
P
O
8
P
O
O
O
O
2b, R =
O
4
OH OH
GDP-Man, 3
Figure 2. Reaction catalyzed by the polyprenol monophosphomannose-dependent a-(1!6)-mannosyltransferase (ManT) and structure of
polyprenol monophosphomannose derivatives used as donor species.

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1743
4, R1 = OH, R2 = OH, R3 = OH, R4 = OH
5, R1 = OCH3, R2 = OH, R3 = OH, R4 = OH
6, R1 = H, R2 = OH, R3 = OH, R4 = OH
7, R1 = OH, R2 = OCH3, R3 = OH, R4 = OH
8, R1 = OH, R2 = H, R3 = OH, R4 = OH
9, R1 = OH, R2 = OH, R3 = OCH3, R4 = OH
10, R1 = OH, R2 = OH, R3 = H, R4 = OH
11, R1 = OH, R2 = OH, R3 = OH, R4 = OCH3
12, R1 = OH, R2 = OH, R3 = OH, R4 = H
R1
O
R4
R3
R2
OH
O
O
HO
HO
OOctyl
OH
O
HO
HO
HO
13, R1 = OCH3, R2 = OH, R3 = OH
14, R1 = H, R2 = OH, R3 = OH
15, R1 = OH, R2 = OCH3, R3 = OH
16, R1 = OH, R2 = H, R3 = OH
17, R1 = OH, R2 = OH, R3 = OCH3
18, R1 = OH, R2 = OH, R3 = H
R1
O
O
R3
R2
OOctyl
Figure 3. Deoxy and methoxy analogs of 4 targeted for synthesis (5–18).
for the development of new classes of anti-mycobacterial
drugs as none of the anti-TB drugs currently in use are
known to target this ManT. However, the polar interac-
tions and steric requirements of the enzyme were only
partially revealed in the previous studies.27,28 To further
characterize the substrate specificity of the enzyme, a
panel of methoxy and deoxy disaccharide analogs
of the known substrate, a-D-Manp-(1!6)-a-D-Manp-
OOctyl (4), was synthesized. As shown in Figure 3, in
each of these analogs a single hydroxyl group of the par-
ent disaccharide was modified by methylation or deoxy-
genation yielding a total of 14 analogs (5–18). In this
paper, we describe the synthesis of these modified oligo-
saccharide analogs.
gent approach was chosen (Fig. 4) that involved as inter-
mediates the protected disaccharides 19 and 20. These
oligosaccharides could, in turn, be obtained from thio-
glycosides 21 and 22 and glycosyl acceptor 23.27
As illustrated in Scheme 1, the donors required for the
synthesis of 5–8, thioglycosides 21 and 22, were obtained
from the known thioglycoside 24,29 which was first pro-
tected as the di-benzylidene acetal using benzaldehyde
dimethyl acetal in the presence of p-toluenesulfonic
acid.30 This reaction afforded a 1:3 mixture of the exo-
isomer 25 and endo-isomer 26 in 72% combined yield.
The diastereomers were discriminated by 2D NOESY
experiments in which the dioxolane acetal hydrogen
showed an NOE to H-2 for compound 26 and to H-4
for compound 25. The more reactive dioxolane ring of
diastereoisomer 25 was regio- and chemoselectively
opened with lithium aluminum hydride and aluminum
trichloride at room temperature to give alcohol 27 in
87% yield.30 The regioselectivity was confirmed by the
subsequent acetylation (vide infra) in which the chemical
shift of H-2 moved from 4.28 to 5.63 ppm. Alternatively,
under the same reaction conditions, the dioxolane ring
of the endo-isomer 26 was opened to give, in addition
2. Results and discussion
2.1. Synthesis of 20- and 30-deoxy and methoxy disac-
charides 5–8
For the preparation of the 20-methoxy (5),27 20-deoxy
(6),27 30-methoxy (7), and 30-deoxy (8) analogs, a diver-
OH
O
Ph
O
OAc
O
Ph
O
O
O
BnO
5 and 6
BnO
O
OBn
O
STol
BnO
21
22
BnO
OOctyl
OBn
O
Ph
O
19
O
AcO
OBn
O
Ph
O
STol
O
HO
HO
BnO
BnO
OBn
O
O
OBn
O
7 and 8
BnO
BnO
OOctyl
OOctyl
20
23
Figure 4. Retrosynthetic analysis of 5–8.

1744
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
OR
O
O
Ph
O
Ph
O
b
O
O
O
O
BnO
STol
STol
H
Ph
OH
O
HO
HO
HO
a
27, R = H
21, R = Ac
25
c
STol
24
O
OBn
O
Ph
O
Ph
O
O
RO
d
O
O
O
STol
STol
Ph
H
28, R = H
22, R = Ac
26
c
Scheme 1. Reagents and conditions: (a) PhCH(OCH3)2, p-TsOH, DMF, 60 ꢁC, 72% (1:3 exo:endo ratio); (b) AlCl3, LiAlH4, CH2Cl2, Et2O, rt, 87%;
(c) Ac2O, pyridine, CH2Cl2, rt, 79% for 21, 94% for 22; (d) AlCl3, LiAlH4, CH2Cl2, Et2O, rt, 0 ꢁC, 66%.
to the expected alcohol 28, three major byproducts as
indicated by TLC. Although the structures of these
byproducts were not unequivocally established, they
are presumably produced as the result of nonspecific
opening or hydrolysis of the dioxolane and dioxane
rings. The formation of these side products could be
minimized by carrying out the reaction at lower temper-
ature (0 ꢁC), which provided alcohol 28 as the major
product in 66% yield. The regioselectivity was estab-
lished by the downfield shift of the H-3 hydrogen
(5.34 ppm) after acetylation. This and the previously
mentioned acetylation reactions were carried out by
treatment of both 27 and 28 with acetic anhydride and
pyridine to give glycosyl donors 21 and 22 in 79% and
94% yields, respectively.
The glycosyl acceptor needed for the synthesis of 5–8,
octyl glycoside 23,27 was synthesized from a known alco-
hol 2927 as illustrated in Scheme 2. Reaction of 29 with
tert-butylchlorodiphenylsilane and imidazole provided
silyl ether 30 in 94% yield. The remaining hydroxyl
groups were protected as benzyl ethers by reaction with
sodium hydride and benzyl bromide, and the silyl group
was removed upon treatment with tetra-n-butylammo-
nium fluoride, which furnished glycosyl acceptor 23 in
91% yield over the two steps.
described in this paper, the a-stereochemistry of the
glycosidic linkages was confirmed by the one-bond
1JC-1,H-1 heteronuclear coupling constants for the
anomeric carbon atoms.33 In all cases, this value was
between 168 and 176 Hz, clearly indicating the a-
stereochemistry.
Subsequent removal of the acetyl groups from these
fully protected disaccharides using sodium methoxide
gave 33 (94% yield) or 34 (89% yield). The target disac-
charides 527 and 7 were prepared by methylation of 33
and 34 with iodomethane and sodium hydride to give
35 and 36 (91% and 76%, respectively), followed by full
deprotection by hydrogenolysis. This two-step sequence
provided 5 in 90% yield from 35 and 7 in 94% yield from
36.
To access the deoxy analog 6,27 disaccharide 33 was
converted to the corresponding xanthate 37 and then
reduced34 with tri-n-butylstannane in the presence of
AIBN yielding 38 in 41% yield. A number of other
byproducts were observed on TLC, but these were not
isolated and characterized. That the deoxygenation
1
had occurred was clearly evident from the H and 13C
1
NMR spectra for 38. In the H NMR spectrum, reso-
nances for H-20ax and H-2e0 q of the expected multiplicity
(ddd) were present at 1.78 and 2.35 ppm, respectively.
In addition, in the 13C NMR spectrum a resonance at
36.4 ppm could be assigned to C-20. The target com-
pound 627 was obtained in 96% yield after deprotection
with hydrogen and palladium hydroxide. As described
for the preparation of 6, a similar series of reactions
starting with 34 gave first xanthate 39 and then deoxy
analog 40 in 37% overall yield. As was the case for 37,
this reaction was accompanied by the formation of a
With these three monosaccharides in hand, coupling
of thioglycosides 21 or 22 with alcohol 23 using NIS/
AgOTf activation31 afforded the corresponding disac-
charides 31 or 32 in 89% and 83% yields, respectively
(Scheme 3). Consistent with earlier work from the Crich
group,32 thioglycoside 22 was found to be a highly
a-selective donor, and we could isolate none of the
b-mannopyranoside. For all the glycosylation reactions
HO
BnO
BnO
OBn
O
OH
O
OH
O
HO
HO
HO
t
-BuPh2SiO
a
b
HO
HO
OOctyl
OOctyl
OOctyl
29
30
23
Scheme 2. Reagents and conditions: (a) t-BuPh2SiCl, imidazole, DMF, 45 ꢁC, 94%; (b) (i) NaH, BnBr, DMF; (ii) n-Bu4NF, THF, rt, 91% over two
steps.

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1745
R
Ph
O
O
O
BnO
a
21 + 23
OBn
O
O
BnO
BnO
R
Ph
O
O
O
BnO
OOctyl
31, R = OAc
33, R = OH
35, R = OCH3
OBn
O
d
O
BnO
BnO
b
c
f
OOctyl
37, R = OC(S)SCH3
e
5
38, R = H
f
6
OBn
O
Ph
O
O
R
a
22 + 23
OBn
O
O
BnO
BnO
OBn
O
Ph
O
O
R
OOctyl
32, R = OAc
34, R = OH
36, R = OCH3
OBn
O
b
c
d
O
BnO
BnO
f
OOctyl
39, R = OC(S)SCH3
e
7
40, R = H
f
8
˚
Scheme 3. Reagents and conditions: (a) NIS, AgOTf, 4 A MS, CH2Cl2, 0 ꢁC, 89% for 31, 83% for 32; (b) NaOCH3, CH3OH, rt, 94% for 33, 89% for
34; (c) NaH, CH3I, DMF, rt, 91% for 35, 76% for 36; (d) NaH, CS2, THF, then CH3I, rt, 96% for 37, 94% for 39; (e) n-Bu3SnH, AIBN, toluene, 41%
for 38, 37% for 40; (f) H2, Pd(OH)2, CH3OH, 90% for 5, 96% for 6, 94% for 7, 91% for 8.
number of byproducts as detected by TLC but which
were not structurally characterized. Presumably these
byproducts result, at least in part, from radical abstrac-
tion of the benzylidene hydrogen in 37 and 39. Removal
of the protecting groups in 40 by hydrogenolysis pro-
vided a 91% yield of 8.
With 42 in hand, disaccharides 9 and 10 were pre-
pared via routes similar to those used for 5–8. Methyl-
ation of 42 yielded disaccharide 44, which was
deprotected to furnish the 40-methoxy analog 9 in 84%
yield. Alternatively, 42 was converted to the correspond-
ing xanthate 45 (96% yield), followed by reduction with
tri-n-butylstannane in the presence of AIBN, to give a
64% yield of 46. The target compound 10 was then
obtained in 87% yield after hydrogenation. To synthe-
size 11, alcohol 43 was methylated affording a 96% yield
of 47, which was then deprotected by hydrogenolysis
providing the target in quantitative yield. Target 12
was also obtained from 43. This disaccharide alcohol
was first reacted with p-toluenesulfonyl chloride and
pyridine to afford the tosylate 48 (90% yield), which
was subsequently converted to 49 in 62% yield upon
reaction with lithium aluminum hydride. In addition
to the expected product 49, alcohol 43, the product of
O–S bond cleavage by the reducing agent, was isolated
in 33% yield. Final deprotection of 49 furnished the
desired deoxy analog 12 (96% yield).
2.2. Synthesis of 40- and 60-deoxy and methoxy
disaccharides 9–12
An intermediate used in the assembly of 5–8, disaccha-
ride 33, was used in the synthesis of the 40- and 60-deoxy
and methoxy disaccharides 9–12, as illustrated in
Scheme 4. The hydroxyl group of 33 was first protected
as the benzyl ether affording 41 in good (94%) yield.
Treatment of 41 with excess triethylsilane and trifluo-
romethanesulfonic acid35 at ꢀ78 ꢁC afforded alcohol
42 in 61% yield. Alternatively, reaction of 41 with lith-
ium aluminum hydride and aluminum trichloride gave
the expected alcohol 43 in 85% yield. The regioselectiv-
ities of both 4,6-O-benzylidene openings were excellent
with less than 4% of the undesired regioisomers. The
regioselectivities of both reactions were based on the
13C NMR spectra of the products, in which the chemical
shift of C-60 of 42 (70.4 ppm) is more downfield than
that of 43 (62.3 ppm).
2.3. Synthesis of 2- and 3-deoxy disaccharides 14 and 16
As illustrated in Scheme 5, a divergent approach
was used for the preparation of the 2- and 3-deoxy

1746
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
R
Ph
O
O
O
BnO
O
OBn
O
BnO
BnO
OOctyl
OBn
O
BnO
R
BnO
33, R = OH
41, R = OBn
a
OBn
O
O
b
BnO
OBn
O
BnO
R
BnO
BnO
OOctyl
d
O
BnO
BnO
OBn
O
42, R = OH
44, R = OCH3
c
f
OOctyl
45, R = OC(S)SCH3
9
e
46, R = H
f
OBn
O
R
BnO
BnO
10
g
OBn
O
BnO
BnO
O
OBn
O
R
BnO
OOctyl
BnO
h
OBn
O
O
BnO
BnO
43, R = OH
47 R = OCH3
c
f
OOctyl
48, R = OTs
49, R = H
i
11
f
12
Scheme 4. Reagents and conditions: (a) NaH, BnBr, DMF, rt, 94%; (b) Et3SiH, TfOH, CH2Cl2, rt, 61%; (c) NaH, CH3I, DMF, rt, 77% for 44, 96%
for 47; (d) NaH, CS2, THF, then CH3I, rt, 96%; (e) n-Bu3SnH, AIBN, toluene, 64%; (f) H2, Pd(OH)2, CH3OH, 84% for 9, 87% for 10, 98% for 11,
96% for 12; (g) AlCl3, LiAlH4, CH2Cl2, Et2O, rt, 85%; (h) TsCl, pyridine, rt, 90%; (i) LiAlH4, ether, rt, 62%.
disaccharide analogs 14 and 16. Reaction of silyl ether
30 (prepared as described in Section 2.1) with 2,2-
dimethoxypropane in the presence of a catalytic amount
of p-TsOH gave a 96% yield of alcohol 50. Benzylation
of the hydroxyl group at C-4 and subsequent removal of
the silyl protecting group provided the expected accep-
tor 51 in 76% yield over the two steps. The donor
required for the synthesis of disaccharide 53, thioglyco-
side 52, was synthesized in 64% yield over two steps
from D-mannose, by first benzoylation and, without
purification, reaction with p-thiocresol and boron triflu-
oride etherate (see Section 3.44).
With these building blocks in place, coupling of
acceptor 51 with the glycosyl donor 52 in a NIS/
TMSOTf-promoted reaction gave disaccharide 53 in
92% yield. Subsequent hydrolysis of the isopropylidene
acetal with 80% aqueous AcOH provided diol 54
(88%), which was converted into a 2:1 mixture of 55
and 56 (63% and 32% yield, respectively) in a two-step
sequence. The significant amount of benzoylation on
O-2 was somewhat surprising as the tin-mediated
benzoylation was envisioned to nearly exclusively take
place at the equatorial 3-hydroxyl group.36 Neverthe-
less, these compounds could be separated by chromato-
graphy, and this approach provided rapid access to both
regioisomers 55 and 56, which led to the target com-
pounds in a few more steps.
Treatment of both 55 and 56 with phenyl chlorothiono-
formate and DMAP gave the corresponding thiocar-
bonyl derivative 57 and 58 in good yields (74% and
70%, respectively). These thiocarbonyl derivatives37
were employed, as opposed to the xanthates we used
in earlier deoxygenations, due to concerns about acyl
migration occurring upon treatment with sodium
hydride, as required for xanthate generation. Reaction
of both derivatives with tri-n-butylstannane and AIBN
provided the deoxy intermediates 59 and 60, in 84%
and 32% yield, respectively. We are unsure as to the ori-
gin of the poor product yield from the deoxygenation of
58, and similar results were observed from repeated
experiments. Subsequent hydrogenolysis of 59 and 60
followed by debenzoylation afforded the corresponding
target deoxy analogs 14 and 16 in 78% and 93% overall
yield, respectively.

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1747
OBz
O
O
O
HO
BnO
BzO
BzO
BzO
t
-BuPh2SiO
HO
O
O
b
a
+
O
O
30
OOctyl
OOctyl
STol
50
51
52
c
OBz
O
BzO
BzO
BzO
OBz
BzO
BzO
BzO
O
O
BnO
O
d
OH
O
O
BnO
HO
O
O
OOctyl
OOctyl
54
53
e
OBz
OBz
BzO
BzO
BzO
BzO
BzO
BzO
O
O
OBz
O
O
BnO
O
BnO
BzO
R
O
R
OOctyl
OOctyl
56, R = OH
58, R = OC(S)OPh
60, R = H
55, R = OH
57, R = OC(S)OPh
59, R = H
f
f
h
h
g
g
14
16
Scheme 5. Reagents and conditions: (a) t-BuPh2SiCl, imidazole, DMF, 45 ꢁC, 96%; (b) (i) NaH, BnBr, DMF; (ii) n-Bu4NF, THF, rt, 76% over two
˚
steps; (c) 52, NIS, TMSOTf, 4 A MS, CH2Cl2, 0 ꢁC, 92%; (d) 80% AcOH/H2O, 50 ꢁC, 88%; (e) (i) n-Bu2SnO, toluene, 110 ꢁC; (ii) BzCl, rt, 63% of 55
and 32% of 56; (f) PhO(C@S)Cl, imidazole, CH3CN, 74% for 57, 70% for 58; (g) n-Bu3SnH, AIBN, toluene, 84% for 59, 32% for 60; (h) (i) H2,
Pd(OH)2, CH3OH, rt; (ii) NaOCH3, CH3OH, rt, 78% for 14 (over 2 steps), 93% for 16 (over two steps).
2.4. Synthesis of 2- and 3-methoxy disaccharides 13 and
15
HO
BnO
BnO
OCH3
O
OOctyl
61
We envisioned that the synthesis of disaccharides 13 and
15 could be achieved from the coupling of either octyl
glycoside 61 or 62 with thioglycoside 52 (Fig. 5). The
preparation of 52 was discussed in Section 2.3, and the
synthesis of 61 and 62 is presented in Scheme 6.
HO
BnO
CH3O
OBn
O
13 and 15
OOctyl
62
The preparation of 61 and 62 started with tetrol 29,27
which was converted to the 2,3:4,6-di-O-benzylidene
derivative 63 upon reaction with benzaldehyde dimethyl
acetal and p-TsOH. The product was obtained as a ꢁ1:1
mixture of exo- and endo-diastereomers in 86% com-
bined yield. Without separation, this mixture was sub-
jected to reductive ring opening with lithium
aluminum hydride and aluminum trichloride at 0 ꢁC to
afford chromatographically separable alcohols 64 and
65 (32% and 36% yield). These compounds were each
independently methylated to furnish compounds 66
and 67 in good yield. Benzylidene ring opening of 66
and 67 with lithium aluminum hydride and aluminum
trichloride (allowing the reaction to proceed overnight
at room temperature as opposed to 1 h at 0 ꢁC as for
the opening of the dioxolane ring in 63) provided the ex-
BzO
BzO
BzO
OBz
O
STol
52
Figure 5. Retrosynthetic analysis of 13 and 15.
pected glycosyl acceptors 61 and 62 in 66% and 57%,
respectively, together with the corresponding 6-O-benzyl
regioisomers (68 and 69). Compared with the dioxane
ring opening of 66, the reaction with 67 was less regiose-
lective, and a significant amount (22%) of regioisomer
69 was also obtained in addition to the desired product
62. These results are consistent with those previously

1748
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
29
R2O
OCH3
O
OR
O
Ph
O
d
a
R1O
O
BnO
BnO
O
OOctyl
OOctyl
Ph
O
b
O
O
61, R1 = Bn, R2 = H
68, R1 = H, R2 = Bn
O
64, R = H
66, R = CH3
c
OOctyl
H
Ph
63
R2O
R1O
OBn
O
OBn
O
e
Ph
O
O
H3CO
RO
OOctyl
OOctyl
62, R1 = Bn, R2 = H
69, R1 = H, R2 = Bn
65, R = H
67, R = CH3
c
Scheme 6. Reagents and conditions: (a) PhCH(OCH3)2, p-TsOH, acetone, rt, 86%; (b) AlCl3, LiAlH4, CH2Cl2, Et2O, rt, 32% of 64 and 36% of 65; (c)
NaH, CH3I, DMF, 94% for 66, 92% for 67; (d) AlCl3, LiAlH4, CH2Cl2, Et2O, rt, 66% of 61 +6% of 68; (e) AlCl3, LiAlH4, CH2Cl2, Et2O, rt, 57% of
62 and 22% of 69.
OBz
O
BzO
BzO
BzO
OBz
O
BzO
BzO
BzO
62
+
61
+
a
a
O
BnO
BnO
OCH3
O
O
BnO
H3CO
OBn
O
52
52
OOctyl
OOctyl
71
70
b
b
15
13
˚
Scheme 7. Reagents and conditions: (a) NIS, TMSOTf, 4 A MS, CH2Cl2, 0 ꢁC, 89% for 70, 96% for 71; (b) (i) NaOCH3, CH3OH, rt; (ii) H2,
Pd(OH)2, CH3OH, rt, 91% and 98% for 13, 87% and 93% for 15.
reported in which the high regioselectivity of the 4,6-O-
benzylidene ring openings under these conditions
requires the presence of a bulky substituent at the C-3
position.30
and DMAP to give the corresponding thiocarbonyl
derivative 73 (84% yield), which was in turn reduced
with tri-n-butylstannane and AIBN providing 74 in
88% yield. This deoxygenated intermediate was desilyl-
ated using tetra-n-butylammonium fluoride to give the
desired monosaccharide 75 in 72% yield.
Glycosylation of alcohols 72 and 75 with thioglyco-
side 52 under the standard activation conditions (NIS/
TMSOTf) afforded disaccharides 76 and 77 in 79%
and 75% yields, respectively. Cleavage of the isopropyl-
idene acetal in 76 yielded diol 78, which was then treated
with sodium methoxide in methanol giving 17 in 81%
overall yield. Similar treatment of 77 provided disaccha-
ride 18 in 94% yield over two steps.
Having in hand all of the monosaccharide building
blocks, the assembly of disaccharides 13 and 15 was
straightforward. Coupling of thioglycoside 52 with alco-
hols 61 and 62 under NIS/TMSOTf activation afforded
the corresponding protected disaccharides 70 and 71 in
89% and 96% yields, respectively (Scheme 7). Subse-
quent removal of the benzoyl and benzyl protecting
groups in 70 and 71 under standard conditions afforded
the target methoxy analogs 13 and 15 in good yields
over the two steps.
2.5. Synthesis of 4-deoxy and 4-methoxy disaccharides 17
and 18
2.6. Conclusion
In conclusion, 14 deoxy and methoxy analogs (5–18) of
the a-D-Manp-(1!6)-a-D-Manp-OOctyl, disaccharide
(4), were synthesized via routes in which the key methyl-
ation or deoxygenation reactions occurred at either the
mono- or disaccharide level. All glycosylation reactions
involved the use of octyl glycoside acceptors and
thioglycoside donors, and the stereochemistry of the
mannopyranoside bond formed was established by mea-
To prepare the 4-deoxy and 4-methoxy analogs 17 and
18 we started with the protected octyl glycoside 50 (see
Section 2.3). As illustrated in Scheme 8, methylation
of the hydroxyl group at C-4 proceeded under standard
conditions to provide an intermediate that was desilyl-
ated using tetra-n-butylammonium fluoride yielding 72
in 89% over two steps. To effect the deoxygenation at
C-4, 50 was reacted with phenyl chlorothionoformate
1
surement of the JC-1,H-1. This panel of compounds will

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1749
OBz
O
BzO
BzO
BzO
O
HO
CH3O
O
e
a
OR1
O
O
O
H3CO
OOctyl
R2O
72
OOctyl
g
76, R1, R2 = C(CH3)2
78, R1 = R2 = H
f
17
18
50
OBz
O
BzO
BzO
BzO
h
O
R'O
R
O
e
b
O
O
O
O
O
OOctyl
OOctyl
73, R = PhO(C=S), R' =
t
-BuPh2Si
c
74, R = H, R' =
75, R = R' = H
t-BuPh2Si
d
77
Scheme 8. Reagents and conditions: (a) (i) NaH, CH3I, DMF; (ii) n-Bu4NF, THF, two steps, 89%; (b) PhO(C@S)Cl, imidazole, CH3CN, 84%; (c) n-
˚
Bu3SnH, AIBN, toluene, 88%; (d) n-Bu4NF, THF, 72%; (e) 52, NIS, TMSOTf, 4 A MS, CH2Cl2, 0 ꢁC, 79% for 76, 75% for 77; (f) 80% AcOH/H2O,
50 ꢁC, 97%; (g) NaOCH3, CH3OH, rt, 86%; (h) (i) 80% AcOH/H2O, 50 ꢁC; (ii) NaOCH3, CH3OH, rt, 94%.
be tested as potential substrates and inhibitors for a
polyprenol monophosphomannose-dependent a-(1!6)-
mannosyltransferase involved in the biosynthesis of the
a-(1!6)-linked mannan core of mycobacterial LAM.
The use of these methoxy and deoxy derivatives will al-
low us to explore the steric requirements and hydrogen-
bonding interactions in the active site of the enzyme.
These studies are currently in progress and will be re-
ported in a future paper.
or 125 MHz and chemical shifts are referenced to inter-
nal CDCl3 (77.23, CDCl3), or CD3OD (48.9, CD3OD).
The stereochemistry at the following mannosylation
1
reactions was proven by measuring JC1–H1 values.
Electrospray-ionization mass spectra (ESIMS) were
recorded on samples suspended in mixtures of THF with
MeOH and added NaCl.
3.2. Octyl 2-O-methyl-a-D-mannopyranosyl-(1!6)-a-D-
mannopyranoside (5)
3. Experimental
Disaccharide 35 (105 mg, 0.11 mmol) was dissolved in
CH3OH (8 mL), and 20% Pd(OH)2 (50 mg) was added.
The mixture was stirred overnight under a H2 atmo-
sphere, and the catalyst was separated by filtration
through a short pad of Celite. The filtrate was concen-
trated to give 5 (50 mg, 90%) as a foam: Rf 0.52 (4:1
3.1. General methods
All reagents used were purchased from commercial
sources and were used without further purification
unless noted. Solvents used in reactions were purified
by successive passage through columns of alumina and
copper under nitrogen. Unless indicated otherwise, all
reactions were performed under a positive pressure of
argon. Reactions were monitored by analytical TLC
on Silica Gel 60-F254 (0.25 mm, Silicycle), and spots
were detected under UV light or by charring with acid-
ified anisaldehyde solution in ethanol. Organic solvents
were evaporated under reduced pressure at <40 ꢁC. Col-
umn chromatography was performed on silica gel (40–
60 lM) or Iatrobeads (Iatron Laboratories, Tokyo).
Optical rotations were measured at 22 2 ꢁC and are
1
CH2Cl2–CH3OH); H NMR (600 MHz, D2O) dH 5.03
(br s, 1H, H-10), 4.82 (br s, 1H, H-1), 3.99 (dd, 1H,
J = 11.1, 4.5 Hz, H-6a), 3.92 (br s, 1H, H-2), 3.84–3.94
(m, 2H, H-30, H-6a0), 3.64–3.80 (m, 7H, H-3, H-4, H-5,
H-6b, H-50, H-6b0, octyl OCH2), 3.77–3.64 (m, 2H, H-
20, H-40), 3.44–3.54 (m, 4H, OCH3, octyl OCH2), 1.55–
1.66 (m, 2H, octyl OCH2CH2), 1.23–1.44 (m, 10H, octyl
CH2), 0.89 (t, 3H, J = 7.2 Hz, octyl CH3); 13C NMR
(125 MHz, D2O) dC 100.4 (C-1), 96.8 (C-10), 80.4 (C-
20), 73.0 (C-50), 71.4 (C-5), 71.3 (C-3), 70.8 (C-30), 70.6
(C-2), 68.1 (octyl OCH2), 67.4 (C-40), 66.8 (C-4), 66.0
(C-6), 61.3 (C-60), 59.3 (OCH3), 31.9 (octyl CH2), 29.3
(octyl CH2), 29.3 (octyl CH2), 29.2 (octyl CH2), 26.2 (oc-
tyl CH2), 22.7 (octyl CH2), 14.0 (octyl CH3). The 1H and
13C NMR spectral data were consistent with that
reported.27
1
in units of (deg mL)/(g dm). H NMR spectra were re-
corded at 500 or 600 MHz, and chemical shifts are refer-
enced to either TMS (0.0, CDCl3) or HOD (4.78, D2O
and CD3OD). 13C NMR spectra were recorded at 100

1750
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
3.3. Octyl 2-O-deoxy-a-D-arabino-hexopyranosyl-(1!6)-
a-D-mannopyranoside (6)
CH3OH); 1H NMR (600 MHz, CD3OD) dH 4.70 (d,
1H, J = 1.2 Hz, H-1), 4.65 (br s, 1H, H-10), 3.89–3.93
(m, 1H, H-6a), 3.62–3.82 (m, 11H, H-2, H-3, H-4, H-
5, H-6b, H-20, H-40, H-50, H-6a0, H-6b0, octyl OCH2),
3.40 (dt, 1H, J = 9.6, 6.3 Hz, octyl OCH2), 1.97 (ddd,
1H, J = 13.2, 3.9, 3.9 Hz, H-30eq), 1.85 (ddd, 1H,
J = 13.2, 11.4, 3.0 Hz, H-30ax), 1.53–1.63 (m, 2H, octyl
OCH2CH2), 1.24–1.42 (m, 10H, octyl CH2), 0.90 (t,
3H, J = 7.2 Hz, octyl CH3); 13C NMR (125 MHz,
CD3OD) dC 101.6 (C-1), 100.1 (C-10), 75.3 (C-50), 73.2
(C-5), 72.9, 72.2, 69.1, 69.1 (C-2, C-3, C-4, C-20), 68.6
(octyl OCH2), 67.3 (C-6), 63.1 (C-60), 62.9 (C-40), 35.9
(C-30), 33.0 (octyl CH2), 30.6 (octyl CH2), 30.5 (octyl
CH2), 30.4 (octyl CH2), 27.4 (octyl CH2), 23.7 (octyl
CH2), 14.4 (octyl CH3). ESIMS: m/z calcd for
[C20H38O10]Na+: 461.2357. Found: 461.2360.
Prepared from disaccharide 38 (102 mg, 0.11 mmol) in
CH3OH (8 mL) and 20% Pd(OH)2 (50 mg) as described
for 5, to give 6 (46 mg, 96%) as a foam: Rf 0.47 (4:1
1
CH2Cl2–CH3OH); H NMR (500 MHz, D2O) dH 5.07
(d, 1H, J = 2.5 Hz, H-10), 4.87 (br s, 1H, H-1), 3.93–
4.04 (m, 3H, H-2, H-6a, H-30), 3.90 (dd, 1H, J = 12.5,
2.3 Hz, H-6a0), 3.64–3.87 (m, 7H, H-3, H-4, H-5, H-
6b, H-50, H-6b0), 3.50–3.58 (m, 1H, octyl OCH2), 3.43
(dd, 1H, J = 9.5, 9.5 Hz, H-40), 2.22 (dd, 1H, J = 12.8,
5.3 Hz, H-20eq), 1.77 (ddd, 1H, J = 12.8, 12.8, 2.5 Hz,
H-20 ), 1.60–1.72 (m, 2H, octyl OCH2CH2), 1.28–1.50
ax
(m, 10H, octyl CH2), 0.93 (t, 3H, J = 6.5 Hz, octyl
CH3); 13C NMR (125 MHz, D2O) dC 100.9 (C-1), 97.9
(C-10), 73.1 (C-50), 72.0, 71.9, 71.8, 71.2, (C-2, C-3, C-
5, C-40), 69.2 (C-30), 68.8 (octyl OCH2), 67.4 (C-4),
66.1 (C-6), 61.6 (C-60), 37.7 (C-20), 32.5 (octyl CH2),
29.9 (octyl CH2), 29.8 (octyl CH2), 29.8 (octyl CH2),
26.7 (octyl CH2), 23.2 (octyl CH2), 14.6 (octyl CH3).
The 1H and 13C NMR spectral data were consistent with
that reported.27
3.6. Octyl 4-O-methyl-a-D-mannopyranosyl-(1!6)-a-D-
mannopyranoside (9)
Prepared from disaccharide 44 (83 mg, 0.082 mmol) in
CH3OH (7 mL) and 20% Pd(OH)2 (40 mg) as described
for 5, after chromatographic purification on Iatrobeads
(4:1 CH2Cl2–CH3OH) to give 9 (32 mg, 84%) as a foam:
Rf 0.42 (4:1, CH2Cl2–CH3OH); [a]D +78.5 (c 0.9,
CH3OH); 1H NMR (600 MHz, CD3OD) dH 4.79 (d,
1H, J = 1.2 Hz, H-10), 4.69 (d, 1H, J = 1.2 Hz, H-1),
3.89 (dd, 1H, J = 10.8, 5.4 Hz, H-6a), 3.75–3.82 (m,
4H, H-2, H-20, H-30, H-6a0), 3.60–3.75 (m, 7H, H-3,
H-4, H-5, H-6b, H-50, H-6b0, octyl OCH2), 3.53 (s,
3H, OCH3), 3.35–3.44 (m, 2H, H-40, octyl OCH2),
1.51–1.63 (m, 2H, octyl OCH2CH2), 1.24–1.44 (m,
10H, octyl CH2), 0.90 (t, 3H, J = 7.2 Hz, octyl CH3);
13C NMR (125 MHz, CD3OD) dC 101.6 (C-1), 101.3
(C-10), 78.4 (C-40), 73.4, 73.4, 73.1, 72.9, 72.7, 72.5,
72.2, 68.6 (C-2, C-3, C-4, C-5, C-20, C-30, C-40, C-50),
68.6 (octyl OCH2), 68.5, 67.5 (C-6), 62.5 (C-60), 60.9
(OCH3), 33.0 (octyl CH2), 30.6 (octyl CH2), 30.5 (octyl
CH2), 30.4 (octyl CH2), 27.4 (octyl CH2), 23.7 (octyl
CH2), 14.5 (octyl CH3). ESIMS: m/z calcd for
[C21H40O11]Na+: 491.2463. Found: 491.2463.
3.4. Octyl 3-O-methyl-a-D-mannopyranosyl-(1!6)-a-D-
mannopyranoside (7)
Prepared from disaccharide 36 (97 mg, 0.11 mmol) in
CH3OH (8 mL) and 20% Pd(OH)2 (50 mg) as described
for 5, to give 7 (49 mg, 94%) as a foam: Rf 0.43 (4:1
CH2Cl2–CH3OH); [a]D +65.4 (c 0.6, CH3OH); 1H
NMR (600 MHz, D2O) dH 4.93 (br s, 1H, H-10), 4.82
(br s, 1H, H-1), 4.19 (br s, 1H, H-20), 3.98 (dd, 1H,
J = 10.8, 4.8 Hz, H-6a), 3.92 (br s, 1H, H-2), 3.87 (app
d, 1H, J = 11.4 Hz, H-6a0), 3.66–3.80 (m, 8H, H-3, H-
4, H-5, H-6b, H-40, H-50, H-6b0, octyl OCH2), 3.46–
3.54 (m, 2H, H-30, octyl OCH2), 3.48 (s, 3H, OCH3),
1.56–1.66 (m, 2H, octyl OCH2CH2), 1.24–1.42 (m,
10H, octyl CH2), 0.88 (t, 3H, J = 7.2 Hz, octyl CH3);
13C NMR (100 MHz, D2O) dC 100.7 (C-1), 100.2 (C-
10), 80.9 (C-30), 73.2 (C-50), 71.8 (C-3/C-5), 71.8 (C-3/
C-5), 70.9 (C-2), 68.4 (octyl OCH2), 67.2 (C-20), 66.6
(C-4), 66.4 (C-6), 66.2 (C-40), 61.5 (C-60), 57.0 (OCH3),
32.2 (octyl CH2), 29.7 (octyl CH2), 29.7 (octyl CH2),
29.6 (octyl CH2), 26.5 (octyl CH2), 23.0 (octyl CH2),
14.4 (octyl CH3). ESIMS: m/z calcd for
[C21H40O11]Na+: 491.2463. Found: 491.2465.
3.7. Octyl 4-deoxy-a-D-lyxo-hexopyranosyl-(1!6)-a-D-
mannopyranoside (10)
Prepared from disaccharide 46 (68 mg, 0.069 mmol) in
CH3OH (6 mL) and 20% Pd(OH)2 (30 mg) as described
for 5, after chromatographic purification on Iatrobeads
(4:1 CH2Cl2–CH3OH) to give 10 (27 mg, 87%) as a foam:
Rf 0.40 (4:1, CH2Cl2–CH3OH); [a]D +71.9 (c 0.7,
CH3OH); 1H NMR (500 MHz, CD3OD) dH 4.85 (d,
1H, J = 1.0 Hz, H-10), 4.70 (d, 1H, J = 1.5 Hz, H-1),
3.97 (ddd, 1H, J = 12.0, 5.0, 3.0 Hz, H-30), 3.85–3.94
(m, 2H, H-6a, H-50), 3.78 (dd, 1H, J = 3.0, 1.5 Hz, H-
2), 3.61–3.72 (m, 6H, H-3, H-4, H-5, H-6b, H-20, octyl
OCH2), 3.55 (d, 2H, J = 5.0 Hz, H-6a0, H-6b0), 3.40
3.5. Octyl 3-O-deoxy-a-D-arabino-hexopyranosyl-(1!6)-
a-D-mannopyranoside (8)
Prepared from disaccharide 40 (71 mg, 0.080 mmol) in
CH3OH (7 mL) and 20% Pd(OH)2 (35 mg) as described
for 5, after chromatographic purification on Iatrobeads
(4:1 CH2Cl2–CH3OH) to give 8 (32 mg, 91%) as a foam:
Rf 0.47 (4:1, CH2Cl2–CH3OH); [a]D +86.6 (c 0.7,

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1751
(dt, 1H, J = 9.5, 6.5 Hz, octyl OCH2), 1.68 (ddd, 1H,
J = 12.0, 12.0, 12.0 Hz, H-40ax), 1.53–1.62 (m, 3H,
CH2), 27.4 (octyl CH2), 23.7 (octyl CH2), 18.0 (C-60),
14.4 (octyl CH3). ESIMS: m/z calcd for
[C20H38O10]Na+: 461.2357. Found: 461.2355.
H-40 , octyl OCH2CH2), 1.24–1.42 (m, 10H, octyl
eq
CH2), 0.90 (t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR
(125 MHz, CD3OD) dC 102.0 (C-10), 101.6 (C-1), 73.2
(C-3/C-4), 72.9 (C-3/C-4), 72.2, (C-2), 70.4 (C-50), 70.2
(C-20), 68.6 (C-5), 68.6 (octyl OCH2), 67.3 (C-6), 66.8
(C-30), 66.0 (C-60), 33.0 (octyl CH2), 31.3 (C-40), 30.6 (oc-
tyl CH2), 30.5 (octyl CH2), 30.4 (octyl CH2), 27.4 (octyl
CH2), 23.7 (octyl CH2), 14.5 (octyl CH3). ESIMS: m/z
calcd for [C20H38O10]Na+: 461.2357. Found: 461.2359.
3.10. Octyl a-D-mannopyranosyl-(1!6)-2-O-methyl-a-D-
mannopyranoside (13)
Disaccharide 70 (251 mg, 0.24 mmol) was dissolved in
CH3OH (20 mL) and NaOCH3 (108 mg) was added.
After 2 h the solution was neutralized with AcOH, and
following concentration, the crude product was purified
by chromatography (10:1, CH2Cl2–CH3OH) to give an
intermediate as a pale-yellow oil (140 mg, 91%). Debenz-
ylation of this intermediate was achieved using CH3OH
(10 mL) and 20% Pd(OH)2 (30 mg) as described for 5 to
give 13 (88 mg, 98%) as a foam: Rf 0.49 (4:1 CH2Cl2–
CH3OH); [a]D +57.6 (c 2.1, CH3OH); 1H NMR
(600 MHz, CD3OD) dH 1H NMR (600 MHz, CD3OD)
dH 4.84 (d, 1H, J = 1.8 Hz, H-1), 4.81 (d, 1H,
J = 1.8 Hz, H-10), 3.86–3.90 (m, 1H, H-6a), 3.84 (dd,
1H, J = 3.0, 1.8 Hz, H-20), 3.81 (dd, 1H, J = 11.7,
2.1 Hz, H-6a0), 3.58–3.74 (m, 9H, H-3, H-4, H-5, H-
6b, H-30, H-40, H-50, H-6b0, octyl OCH2), 3.44 (s, 3H,
OCH3), 3.43 (dt, 1H, J = 9.6, 6.0 Hz, octyl OCH2),
3.39 (dd, 1H, J = 3.6, 1.8 Hz, H-2), 1.53–1.63 (m, 2H,
octyl OCH2CH2), 1.25–1.43 (m, 10H, octyl CH2), 0.90
(t, 3H, J = 7.2 Hz, octyl CH3); 13C NMR (125 MHz,
CD3OD) dC 101.5 (C-1), 98.3 (C-10), 82.2 (C-2), 74.4
(C-50), 73.2 (C-5), 72.7 (C-30), 72.7 (C-3), 72.1 (C-20),
68.8 (C-4/C-40), 68.7 (octyl OCH2), 68.6 (C-4/C-40),
67.4 (C-6), 62.9 (C-60), 59.3 (OCH3), 33.0 (octyl CH2),
30.7 (octyl CH2), 30.5 (octyl CH2), 30.4 (octyl CH2),
27.4 (octyl CH2), 23.7 (octyl CH2), 14.4 (octyl CH3).
ESIMS: m/z calcd for [C21H40O11]Na+: 491.2463.
Found: 491.2462.
3.8. Octyl 6-O-methyl-a-D-mannopyranosyl-(1!6)-a-D-
mannopyranoside (11)
Prepared from disaccharide 47 (93 mg, 0.092 mmol) in
CH3OH (8 mL) and 20% Pd(OH)2 (45 mg) as described
for 5, to give 11 (42 mg, 98%) as a foam: Rf 0.38 (4:1
CH2Cl2–CH3OH); [a]D +67.0 (c 2.1, CH3OH); 1H
NMR (600 MHz, CD3OD) dH 4.79 (d, 1H, J = 1.5 Hz,
H-10), 4.69 (d, 1H, J = 1.2 Hz, H-1), 3.86–3.91 (m, 1H,
H-6a), 3.83 (dd, 1H, J = 3.3, 1.5 Hz, H-20), 3.78 (dd,
1H, J = 3.0, 1.2 Hz, H-2), 3.75 (ddd, 1H, J = 9.6, 6.0,
2.1 Hz, H-50), 3.56–3.75 (m, 9H, H-3, H-4, H-5, H-6b,
H-30, H-40, H-6a0, H-6b0, octyl OCH2), 3.37–3.42 (m,
4H, OCH3, octyl OCH2), 1.51–1.63 (m, 2H, octyl
OCH2CH2), 1.24–1.44 (m, 10H, octyl CH2), 0.90 (t,
3H, J = 7.2 Hz, octyl CH3); 13C NMR (125 MHz,
CD3OD) dC 101.6 (C-10), 101.5 (C-1), 73.4 (C-60), 73.1,
73.0 (C-3, C-30), 72.9 (C-5), 72.7 (C-50), 72.2 (C-2), 72.0
(C-20), 68.8 (C-4/C-40), 68.6 (octyl OCH2), 68.5 (C-4/C-
40), 67.5 (C-6), 59.5 (OCH3), 33.0 (octyl CH2), 30.6 (octyl
CH2), 30.5 (octyl CH2), 30.4 (octyl CH2), 27.4 (octyl
CH2), 23.7 (octyl CH2), 14.5 (octyl CH3). ESIMS: m/z
calcd for [C21H40O11]Na+: 491.2463. Found: 491.2458.
3.9. Octyl 6-deoxy-a-D-mannopyranosyl-(1!6)-a-D-
3.11. Octyl a-D-mannopyranosyl-(1!6)-2-deoxy-a-D-
arabino-hexopyranoside (14)
mannopyranoside (12)
Prepared from disaccharide 49 (77 mg, 0.079 mmol) in
CH3OH (7 mL) and 20% Pd(OH)2 (35 mg) as described
for 5, to give 12 (33 mg, 96%) as a foam: Rf 0.48 (4:1
CH2Cl2–CH3OH); [a]D +66.9 (c 1.2, CH3OH); 1H
NMR (600 MHz, CD3OD) dH 4.73 (d, 1H, J = 2.0 Hz,
H-10), 4.70 (d, 1H, J = 1.5 Hz, H-1), 3.82–3.87 (m, 2H,
H-6a, H-20), 3.78 (dd, 1H, J = 3.0, 1.5 Hz, H-2), 3.60–
3.73 (m, 7H, H-3, H-4, H-5, H-6b, H-30, H-50, octyl
OCH2), 3.40 (dt, 1H, J = 9.6, 6.3, 6.3 Hz, octyl
OCH2), 3.36 (dd, 1H, J = 9.5, 9.5 Hz, H-40), 1.51–1.63
(m, 2H, octyl OCH2CH2), 1.24–1.42 (m, 10H, octyl
CH2), 1.25 (d, 3H, J = 6.5 Hz, H-60), 0.89 (t, 3H,
J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz, CD3OD)
dC 101.6 (C-1), 101.4 (C-10), 74.1 (C-40), 73.1 (C-3),
72.9 (C-30), 72.5 (C-4), 72.2 (C-2, C-20), 69.6 (C-50),
68.6 (C-5), 68.6 (octyl OCH2), 67.4 (C-6), 33.0 (octyl
CH2), 30.6 (octyl CH2), 30.5 (octyl CH2), 30.4 (octyl
Debenzylation of disaccharide 59 (107 mg, 0.10 mmol)
was achieved using 20% Pd(OH)2 (30 mg) in CH3OH
(8 mL) as described for 5 to obtain a white solid inter-
mediate, which was dissolved in CH3OH (10 mL) before
NaOCH3 (54 mg) was added. After stirring for 2 h, the
solution was neutralized with AcOH and concentrated,
and the crude product was purified by chromatography
on Iatrobeads (4:1 CH2Cl2–CH3OH) to give 14 (35 mg,
78%) as a foam: Rf 0.43 (4:1, CH2Cl2–CH3OH); [a]D
1
+90.4 (c 2.0, CH3OH); H NMR (600 MHz, CD3OD)
dH 4.84 (d, 1H, J = 1.2 Hz, H-1), 4.80 (d, 1H,
J = 1.8 Hz, H-10), 3.91 (dd, 1H, J = 11.1, 5.1 Hz, H-
6a), 3.78–3.84 (m, 3H, H-3, H-20, H-6a0), 3.60–3.73
(m, 7H, H-5, H-6b, H-30, H-40, H-50, H-6b0, octyl
OCH2), 3.35 (dt, 1H, J = 9.6, 6.3 Hz, octyl OCH2),
3.28 (dd, 1H, J = 9.6, 9.6 Hz, H-4), 2.04 (ddd, 1H,
J = 13.2, 5.4, 1.2 Hz, H-2eq), 1.51–1.62 (m, 3H, H-2ax,

1752
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
octyl OCH2CH2), 1.24–1.42 (m, 10H, octyl CH2), 0.90
(t, 3H, J = 6.9 Hz, octyl CH3); 13C NMR (125 MHz,
CD3OD) dC 101.5 (C-10), 98.7 (C-1), 74.4 (C-30), 73.2
(C-4), 72.7 (C-40/C-5), 72.7 (C-40/C-5), 72.1 (C-20),
70.2 (C-3), 68.6 (C-50), 68.4 (octyl OCH2), 67.3 (C-6),
62.9 (C-60), 39.0 (C-2), 33.0 (octyl CH2), 30.7 (octyl
CH2), 30.6 (octyl CH2), 30.4 (octyl CH2), 27.5 (octyl
CH2), 23.7 (octyl CH2), 14.4 (octyl CH3). ESIMS: m/z
calcd for [C20H38O10]Na+: 461.2357. Found: 461.2359.
3.0 Hz, H-3ax), 1.53–1.64 (m, 2H, octyl OCH2CH2),
1.25–1.44 (m, 10H, octyl CH2), 0.90 (t, 3H,
J = 7.2 Hz, octyl CH3); 13C NMR (125 MHz, CD3OD)
dC 101.4 (C-10), 100.3 (C-1), 74.3 (C-40/C-5), 74.1 (C-
40/C-5), 72.7 (C-30), 72.2 (C-20), 69.2 (C-2), 68.6 (C-50),
68.4 (octyl OCH2), 67.6 (C-6), 62.9 (C-4), 62.8 (C-60),
36.3 (C-3), 33.0 (octyl CH2), 30.7 (octyl CH2), 30.6 (oc-
tyl CH2), 30.4 (octyl CH2), 27.5 (octyl CH2), 23.7 (octyl
CH2), 14.4 (octyl CH3). ESIMS: m/z calcd for
[C20H38O10]Na+: 461.2357. Found: 461.2360.
3.12. Octyl a-D-mannopyranosyl-(1!6)-3-O-methyl-a-D-
mannopyranoside (15)
3.14. Octyl a-D-mannopyranosyl-(1!6)-4-O-methyl-a-D-
mannopyranoside (17)
Debenzoylation of disaccharide 71 (252 mg, 0.28 mmol)
using NaOCH3 (108 mg) in CH3OH (25 mL) as
described for 13 gave a pale-yellow oil intermediate
(133 mg, 87%). A portion of this intermediate (60 mg,
0.092 mmol) was debenzylated in CH3OH (5 mL) and
20% Pd(OH)2 (15 mg) to give 15 (41 mg, 93%) as a
foam: Rf 0.31 (4:1 CH2Cl2–CH3OH); [a]D +70.4 (c 1.2,
CH3OH); 1H NMR (600 MHz, CD3OD) dH 4.81 (d,
1H, J = 1.8 Hz, H-10), 4.74 (d, 1H, J = 1.8 Hz, H-1),
3.99 (dd, 1H, J = 3.2, 1.8 Hz, H-2), 3.89 (dd, 1H,
J = 11.1, 5.8 Hz, H-6a), 3.83 (dd, 1H, J = 3.3, 1.8 Hz,
H-20), 3.81 (dd, 1H, J = 12.0, 1.8 Hz, H-6a0), 3.61–3.74
(m, 8H, H-4, H-5, H-6b, H-30, H-40, H-50, H-6b0, octyl
OCH2), 3.44 (s, 3H, OCH3), 3.41 (dt, 1H, J = 10.2,
6.3 Hz, octyl OCH2), 3.33 (dd, 1H, J = 9.3, 3.2 Hz, H-
3), 1.54–1.64 (m, 2H, octyl OCH2CH2), 1.25–1.43 (m,
10H, octyl CH2), 0.90 (t, 3H, J = 7.2 Hz, octyl CH3);
13C NMR (125 MHz, CD3OD) dC 101.6 (C-1), 101.4
(C-10), 82.6 (C-3), 74.3 (C-50), 73.1 (C-5), 72.7 (C-4),
72.1 (C-20), 68.7 (octyl OCH2), 68.6 (C-30), 68.1 (C-2),
67.4 (C-40), 67.3 (C-6), 62.9 (C-60), 57.4 (OCH3), 33.0
(octyl CH2), 30.6 (octyl CH2), 30.5 (octyl CH2), 30.4
(octyl CH2), 27.4 (octyl CH2), 23.7 (octyl CH2), 14.4
(octyl CH3). ESIMS: m/z calcd for [C21H40O11]Na+:
491.2463. Found: 491.2464.
Prepared from diol 78 (69 mg, 0.078 mmol) in CH3OH
(7 mL) and NaOCH3 (38 mg) as described for 13 to give
17 (32 mg, 86%) as a foam: Rf 0.44 (4:1 CH2Cl2–
CH3OH); [a]D +84.3 (c 0.6, CH3OH); 1H NMR
(600 MHz, CD3OD) dH 4.85 (d, 1H, J = 1.8 Hz, H-10),
4.67 (br s, 1H, H-1), 3.86–3.90 (m, 2H, H-6a, H-20),
3.82 (dd, 1H, J = 11.7, 2.1 Hz, H-6a0), 3.60–3.76 (m,
8H, H-2, H-3, H-6b, H-30, H-40, H-50, H-6b0, octyl
OCH2), 3.58 (ddd, 1H, J = 10.2, 5.4, 1.8 Hz, H-5),
3.54 (s, 3H, OCH3), 3.34–3.41 (m, 2H, H-4, octyl
OCH2), 1.51–1.61 (m, 2H, octyl OCH2CH2), 1.24–1.41
(m, 10H, octyl CH2), 0.89 (t, 3H, J = 7.2 Hz, octyl
CH3); 13C NMR (125 MHz, CD3OD) dC 101.8 (C-10),
101.5 (C-1), 78.7 (C-4), 74.6 (C-30/C-50), 72.9, 72.7,
72.5 (C-2, C-3, C-40), 72.3 (C-5), 72.1 (C-20), 68.6 (C-
30/C-50), 68.6 (octyl OCH2), 67.5 (C-6), 62.9 (C-60),
61.1 (OCH3), 33.0 (octyl CH2), 30.6 (octyl CH2), 30.5
(octyl CH2), 30.4 (octyl CH2), 27.4 (octyl CH2), 23.7 (oc-
tyl CH2), 14.5 (octyl CH3). ESIMS: m/z calcd for
[C21H40O11]Na+: 491.2463. Found: 491.2466.
3.15. Octyl a-D-mannopyranosyl-(1!6)-4-deoxy-a-D-
lyxo-hexopyranoside (18)
Disaccharide 77 (99 mg, 0.11 mmol) was dissolved in
80% AcOH–H2O (2 mL) and heated at 50 ꢁC overnight.
The solution was then diluted with EtOAc (20 mL),
washed with satd aq NaHCO3 (2 · 5 mL), dried
(MgSO4), and concentrated to a colorless residue that
was reacted with NaOCH3 (54 mg) in CH3OH (10 mL)
as described for 13 to give 18 (46 mg, 94% over two
steps) as a foam: Rf 0.38 (4:1 CH2Cl2–CH3OH); [a]D
3.13. Octyl a-D-mannopyranosyl-(1!6)-3-deoxy-a-D-
arabino-hexopyranoside (16)
As described for 14, disaccharide 60 (32 mg,
0.030 mmol) was debenzylated in CH3OH (3 mL) and
20% Pd(OH)2 (10 mg) to give a white solid intermediate,
which was reacted with NaOCH3 (22 mg) in CH3OH
(4 mL) to give 16 (12 mg, 93%) as a foam: Rf 0.45 (4:1
CH2Cl2–CH3OH); [a]D +65.2 (c 0.6, CH3OH); 1H
NMR (600 MHz, CD3OD) dH 4.81 (d, 1H, J = 1.8 Hz,
H-10), 4.54 (br s, 1H, H-1), 3.86 (dd, 1H, J = 10.8,
6.0 Hz, H-6a), 3.84 (dd, 1H, J = 3.6, 1.8 Hz, H-20),
3.77–3.83 (m, 2H, H-4, H-6a0), 3.74–3.76 (m, 1H, H-
2), 3.69–3.74 (m, 4H, H-6b, H-30, H-6b0, octyl OCH2),
3.62–3.67 (m, 3H, H-5, H-40, H-50), 3.41 (dt, 1H,
J = 9.6, 6.3 Hz, octyl OCH2), 1.99 (ddd, 1H, J = 13.2,
3.0, 3.0 Hz, H-3eq), 1.80 (ddd, 1H, J = 13.2, 11.4,
1
+64.7 (c 2.3, CH3OH); H NMR (500 MHz, CD3OD)
dH 4.78 (d, 1H, J = 2.0 Hz, H-10), 4.75 (d, 1H,
J = 1.5 Hz, H-1), 3.87–3.94 (m, 2H, H-3, H-5), 3.80–
3.84 (m, 2H, H-20, H-6a0), 3.76 (dd, 1H, J = 10.6,
6.5 Hz, H-6a), 3.56–3.73 (m, 6H, H-2, H-30, H-40, H-
50, H-6b0, octyl OCH2), 3.46 (dd, 1H, J = 10.6, 3.8 Hz,
H-6b), 3.38 (dt, 1H, J = 9.6, 6.8 Hz, octyl OCH2), 1.73
(ddd, 1H, J = 12.0 Hz, H-4ax), 1.52–1.62 (m, 3H, H-
4eq, octyl OCH2CH2), 1.24–1.41 (m, 10H, octyl CH2),
0.90 (t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1753
(125 MHz, CD3OD) dC 102.2 (C-1), 101.4 (C-10), 74.5
(C-30), 72.7 (C-40), 72.1 (C-20), 70.7 (C-6), 70.3 (C-2),
68.7 (C-5/C-50), 68.6 (C-5/C-50), 68.5 (octyl OCH2),
66.9 (C-3), 33.0 (octyl CH2), 31.6 (C-4), 30.6 (octyl
CH2), 30.5 (octyl CH2), 30.4 (octyl CH2), 27.4 (octyl
CH2), 23.7 (octyl CH2), 14.5 (octyl CH3). ESIMS: m/z
calcd for [C20H38O10]Na+: 461.2357. Found: 461.2357.
NMR (100 MHz, CDCl3) dC 170.2 (C@O), 138.1 (Ar),
137.3 (Ar), 137.3 (Ar), 132.5 (2 · Ar), 130.0 (2 · Ar),
129.7 (Ar), 129.1 (Ar), 128.6 (2 · Ar) 128.3 (2 · Ar),
128.2 (Ar), 128.1 (2 · Ar), 126.3 (2 · Ar), 101.8 (benzyl-
idene CH), 86.7 (C-1), 77.5 (C-2/C-4), 76.3 (C-2/C-4),
73.0 (PhCH2), 70.5 (C-3), 68.5 (C-6), 65.3 (C-5), 21.2
(SPhCH3), 21.0 (C(O)CH3). ESIMS: m/z calcd for
[C29H30O6S]Na+: 529.1655. Found: 529.1652.
3.16. p-Tolyl 2-O-acetyl-3-O-benzyl-4,6-O-benzylidene-1-
thio-a-D-mannopyranoside (21)
3.18. Octyl 2,3,4-tri-O-benzyl-a-D-mannopyranoside (23)
Monosaccharide 27 (2.2 g, 4.7 mmol) was dissolved in
CH2Cl2 (50 mL), and pyridine (7.2 mL) and acetic anhy-
dride (3.6 mL) were added. The reaction mixture was
stirred overnight and then diluted with CH2Cl2
(150 mL), before being washed with 1 M HCl
(3 · 50 mL), satd aq NaHCO3 (50 mL), water (50 mL),
dried (MgSO4), and concentrated. The crude product
was purified by chromatography (6:1 hexane–EtOAc)
to give 21 (1.89 g, 79%) as a foam: Rf 0.42 (6:1 hex-
ane–EtOAc); [a]D +119.5 (c 7.0, CHCl3); 1H NMR
(400 MHz, CDCl3) dH 7.52–7.55 (m, 2H, ArH), 7.29–
7.43 (m, 10H, ArH), 7.13 (d, 2H, J = 8.4 Hz, ArH),
5.64 (s, 1H, benzylidene H), 5.63 (dd, 1H, J = 3.2,
1.2 Hz, H-2), 5.40 (d, 1H, J = 1.2 Hz, H-1), 4.75 (d,
1H, J = 12.0 Hz, PhCH2), 4.70 (d, 1H, J = 12.0 Hz,
PhCH2), 4.37 (ddd, 1H, J = 10.0, 9.6, 4.8 Hz, H-5),
4.25 (dd, 1H, J = 10.4, 4.8 Hz, H-6a), 4.15 (dd, 1H,
J = 9.6, 9.6 Hz, H-4), 4.03 (dd, 1H, J = 9.6, 3.2 Hz, H-
3), 3.87 (dd, 1H, J = 10.4, 10.0 Hz, H-6b), 2.34 (s, 3H,
SPhCH3), 2.16 (s, 3H, C(O)CH3); 13C NMR
(100 MHz, CDCl3) dC 169.9 (C@O), 138.3 (Ar), 137.6
(Ar), 137.3 (Ar), 132.6 (2 · Ar), 129.9 (2 · Ar), 129.1
(Ar), 128.8 (Ar), 128.3 (2 · Ar), 128.1 (2 · Ar), 127.7
(3 · Ar), 126.0 (2 · Ar), 101.5 (benzylidene CH), 87.4
(C-1), 78.4 (C-4), 74.0 (C-3), 72.2 (PhCH2), 71.2 (C-2),
68.3 (C-6), 65.0 (C-5), 21.1 (PhCH3), 20.9 (C(O)CH3).
ESIMS: m/z calcd for [C29H30O6S]Na+: 529.1655.
Found: 529.1652.
Triol 30 (4.18 g, 7.87 mmol) was dissolved in DMF
(25 mL), and BnBr (6.0 mL, 48.0 mmol) was added.
The solution was cooled in an ice bath, and 60% NaH
in mineral oil (2.05 g, 51.3 mmol) was added portion-
wise, and the mixture was warmed to room temperature.
After 3 h, the reaction was quenched by the addition of
CH3OH (15 mL), diluted with EtOAc (90 mL), washed
with water (3 · 40 mL), brine (40 mL) and dried
(MgSO4), filtered, and concentrated to a pale-yellow
oil. The crude product was dissolved in THF (50 mL),
1.0 M tetra-n-butylammonium fluoride in THF
(16.0 mL, 16.0 mmol) was added, and the solution was
stirred at room temperature overnight. The solvent
was evaporated, and the residue was purified by chro-
matography (4:1, hexane–EtOAc) to give 23 (4.03 g,
91% over two steps) as a colorless oil: Rf 0.24 (4:1, hex-
ane–EtOAc); 1H NMR (500 MHz, CDCl3) dH 7.27–7.44
(m, 15H, ArH), 4.96 (d, 1H, J = 11.0 Hz, PhCH2), 4.81
(d, 1H, J = 11.0 Hz, PhCH2), 4.81 (d, 1H, J = 1.5 Hz,
H-1), 4.64–4.74 (m, 4H, PhCH2), 4.00 (dd, 1H,
J = 9.5, 9.5 Hz, H-4), 3.95 (dd, 1H, J = 9.5, 3.0 Hz, H-
3), 3.86 (ddd, 1H, J = 11.5, 3.0 Hz, H-6a), 3.76–3.83
(m, 2H, H-2, H-6b), 3.64–3.70 (m, 1H, H-5), 3.63 (dt,
1H, J = 9.5, 6.5 Hz, octyl OCH2), 3.34 (dt, 1H,
J = 9.5, 6.5 Hz, octyl OCH2), 2.09 (dd, 1H, J = 7.5,
5.5 Hz, OH), 1.46–1.78 (m, 2H, octyl OCH2CH2),
1.24–1.38 (m, 10H, octyl CH2), 0.91 (t, 3H,
J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz, CDCl3)
dC 138.6 (Ar), 138.4 (Ar), 138.4 (Ar), 128.4 (3 · Ar),
128.4 (2 · Ar), 127.8 (2 · Ar), 127.7 (2 · Ar), 127.7
(2 · Ar), 127.6 (2 · Ar), 127.6 (2 · Ar), 98.2 (C-1), 80.3
(C-3), 75.3 (PhCH2), 75.1 (C-2, C-4), 72.9 (PhCH2),
72.1 (C-5), 67.7 (octyl OCH2), 62.5 (C-6), 31.8 (octyl
CH2), 29.4 (octyl CH2), 29.4 (octyl CH2), 29.2
(octyl CH2), 26.1 (octyl CH2), 22.7 (octyl CH2), 14.1
3.17. p-Tolyl 3-O-acetyl-2-O-benzyl-4,6-O-benzylidene-1-
thio-a-D-mannopyranoside (22)
Prepared from monosaccharide 28 (1.8 g, 3.9 mmol),
pyridine (7.0 mL) and acetic anhydride (3.5 mL) in
CH2Cl2 (40 mL) as described for 21, to give 22 (1.83 g,
94%) as a foam: Rf 0.45 (4:1 hexane–EtOAc); [a]D
1
(octyl CH3). H and 13C NMR spectral data were con-
1
+76.3 (c 5.4, CHCl3); H NMR (400 MHz, CDCl3) dH
sistent with that reported.27
7.50–7.53 (m, 2H, ArH), 7.33–7.42 (m, 10H, ArH),
7.16 (d, 2H, J = 8.0 Hz, ArH), 5.61 (s, 1H, benzylidene
H), 5.51 (d, 1H, J = 1.2 Hz, H-1), 5.34 (dd, 1H,
J = 10.4, 3.2 Hz, H-3), 4.70 (d, 1H, J = 12.0Hz,
PhCH2), 4.63 (d, 1H, J = 12.0 Hz, PhCH2), 4.44 (ddd,
1H, J = 10.0, 10.0, 4.8 Hz, H-5), 4.25–4.30 (m, 3H, H-
2, H-4, H-6a), 3.90 (dd, 1H, J = 10.0, 10.0 Hz, H-6b),
2.37 (s, 3H, SPhCH3), 2.06 (s, 3H, C(O)CH3); 13C
3.19. p-Tolyl exo(phenyl)-2,3:4,6-di-O-benzylidene-1-
thio-a-D-mannopyranoside (25) and 4-methylphenyl
endo(phenyl)-2,3:4,6-di-O-benzylidene-1-thio-a-D-manno-
pyranoside (26)
Tetraol 2429 (2.0 g, 7.0 mmol) was dissolved in DMF
(5.0 mL) and benzaldehyde dimethyl acetal (1.5 mL,

1754
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
10.0 mmol) and p-TsOH (21 mg, 0.11 mmol) were
added. The reaction mixture was rotated under reduced
pressure at 60 ꢁC on a rotary evaporator. After 2 h addi-
tional DMF (50 mL), benzaldehyde dimethyl acetal
(1.5 mL, 10.0 mmol), and p-TsOH (21 mg, 0.11 mmol)
were added, and stirring was continued for 3 h. The
reaction mixture was neutralized with satd aq NaHCO3,
diluted with CH2Cl2 (100 mL), washed with water
(3 · 50 mL), dried (MgSO4), and concentrated. Recrys-
talization of the crude product from 1:1, acetone–EtOH
(300 mL) gave a mixture of 25 and 26. A second recrys-
talization of this material afforded a mixture of 25 and
26 in 23:1 ratio (584 mg, 18%). The mother liquor was
concentrated, and the resulting solid was recrystalized
from 1:1, acetone–EtOH (75 mL) to give crystalline of
26 and 25 in 20:1 ratio (964 mg, 30%). The mother
liquor was concentrated and purified by chromatogra-
phy (9:1, hexane–EtOAc) to give 26 and 25 in 12:1 ratio
(773 mg, 24%).
C, 69.92; H, 5.72; S, 7.02. ESIMS: m/z calcd for
[C27H26O5S]Na+: 485.1393. Found: 485.1395.
3.20. p-Tolyl 3-O-benzyl-4,6-O-benzylidene-1-thio-a-D-
mannopyranoside (27)
AlCl3 (0.16 g, 1.2 mmol) was dissolved in prechilled
Et2O (4 mL) and stirred for 10 min before LiAlH4
(1.2 mL of 1.0 M solution in ether) was added. This mix-
ture was stirred for an additional 10 min before addition
to 25 (480 mg, 1.0 mmol) in 1:1, CH2Cl2–Et2O (15 mL).
The reaction mixture was stirred for 1 h and then
quenched by the addition of EtOAc followed by water.
The reaction mixture was diluted with EtOAc (60 mL),
washed with water (3 · 20 mL), dried (MgSO4), and
concentrated to a light-yellow oil that was purified by
chromatography (4:1, hexane–EtOAc) to give 27
(419 mg, 87%) as a light yellow oil: Rf 0.21 (4:1 hex-
ane–EtOAc); [a]D +222.2 (c 2.8, CHCl3); 1H NMR
(500 MHz, CDCl3) dH 7.50–7.55 (m, 2H, ArH), 7.31–
7.42 (m, 10H, ArH), 7.13 (d, 2H, J = 8.5 Hz, ArH),
5.63 (s, 1H, benzylidene H), 5.53 (d, 1H, J = 1.3 Hz,
H-1), 4.90 (d, 1H, J = 11.8 Hz, PhCH2), 4.75 (d, 1H,
J = 11.8 Hz, PhCH2), 4.36 (ddd, 1H, J = 10.4, 9.5,
5.0 Hz, H-5), 4.28 (dd, 1H, J = 3.4, 1.3 Hz, H-2), 4.22
(dd, 1H, J = 10.4, 5.0 Hz, H-6a), 4.19 (dd, 1H,
J = 9.5, 9.5 Hz, H-4), 3.98 (dd, 1H, J = 9.5, 3.4 Hz, H-
3), 3.86 (dd, 1H, J = 10.4, 10.4 Hz, H-6b), 2.85 (br s,
1H, OH), 2.34 (s, 3H, PhCH3); 13C NMR (125 MHz,
CDCl3) dC 138.0 (Ar), 137.8 (Ar), 137.5 (Ar), 132.4
(2 · Ar), 129.9 (2 · Ar), 129.4 (Ar), 129.0 (Ar), 128.5
(2 · Ar), 128.2 (2 · Ar), 128.0 (Ar), 127.9 (2 · Ar),
126.1 (2 · Ar), 101.6 (benzylidene CH), 88.2 (C-1),
79.1 (C-4), 75.7 (C-3), 73.2 (PhCH2), 71.4 (C-2), 68.6
(C-6), 64.5 (C-5), 21.1 (PhCH3). ESIMS: m/z calcd for
[C27H28O5S]Na+: 487.1550. Found: 487.1552.
3.19.1. Data for 25. 1H NMR (500 MHz, CDCl3) dH
7.53–7.58 (m, 2H, ArH), 7.44–7.59 (m, 2H, ArH),
7.36–7.41 (m, 8H, ArH), 7.15 (d, 2H, J = 8.0 Hz,
ArH), 6.31 (s, 1H, dioxolane H), 5.80 (s, 1H, H-1),
5.65 (s, 1H, dioxane H), 4.68 (dd, 1H, J = 9.0, 5.5 Hz,
H-3), 4.38 (d, 1H, J = 5.5 Hz, H-2), 4.34 (ddd, 1H,
J = 10.5, 9.0, 5.0 Hz, H-5), 4.25 (dd, 1H, J = 10.5,
5.0 Hz, H-6a), 3.98 (dd, 1H, J = 9.0, 9.0 Hz, H-4), 3.79
(dd, 1H, J = 10.5, 10.5 Hz, H-6b), 2.35 (s, 3H, PhCH3);
13C NMR (125 MHz, CDCl3) dC 138.5 (Ar), 138.5 (Ar),
137.1 (Ar), 133.1 (2 · Ar), 130.0 (2 · Ar), 129.2 (Ar),
129.2 (Ar), 128.7 (Ar), 128.4 (2 · Ar), 128.3 (2 · Ar),
126.3 (2 · Ar), 126.0 (2 · Ar), 103.1 (dioxolane CH),
102.0 (dioxane CH), 85.0 (C-1), 77.8 (C-4), 75.9 (C-2),
75.3 (C-3), 68.6 (C-6), 61.6 (C-5), 21.2 (PhCH3). Anal.
Calcd for C27H26O5S (462.56): C, 70.11; H, 5.61; S,
6.93. Found: C, 69.93; H, 5.70; S, 7.01. ESIMS: m/z
calcd for [C27H26O5S]Na+: 485.1393. Found: 485.1391.
3.21. p-Tolyl 2-O-benzyl-4,6-O-benzylidene-1-thio-a-D-
mannopyranoside (28)
3.19.2. Data for 26. 1H NMR (500 MHz, CDCl3) dH
7.50–7.55 (m, 4H, ArH), 7.34–7.43 (m, 8H, ArH), 7.15
(d, 2H, J = 7.5 Hz, ArH), 5.99 (s, 1H, dioxolane H),
5.86 (s, 1H, H-1), 5.51 (s, 1H, dioxane H), 4.54 (dd,
1H, J = 8.0, 8.0 Hz, H-3), 4.49 (d, 1H, J = 8.0 Hz, H-
2), 4.27 (ddd, 1H, J = 10.5, 10.0, 5.0 Hz, H-5), 4.19
(dd, 1H, J = 10.5, 5.0 Hz, H-6a), 3.81 (dd, 1H,
J = 10.0, 8.0 Hz, H-4), 3.69 (dd, 1H, J = 10.5, 10.5 Hz,
H-6b), 2.35 (s, 3H, PhCH3); 13C NMR (125 MHz,
CDCl3) dC 138.5 (Ar), 137.2 (Ar), 137.0 (Ar), 133.2
(2 · Ar), 130.0 (2 · Ar), 130.0 (Ar), 129.5 (Ar), 129.1
(Ar), 128.5 (2 · Ar), 128.2 (2 · Ar), 126.5 (2 · Ar),
126.2 (2 · Ar), 104.1 (dioxolane CH), 101.8 (dioxane
CH), 84.5 (C-1), 80.8 (C-4), 78.6 (C-2), 74.0 (C-3), 68.6
(C-6), 61.7 (C-5), 21.2 (PhCH3). Anal. Calcd for
C27H26O5S (462.56): C, 70.11; H, 5.61; S, 6.93. Found:
Prepared from a solution of AlCl3 (0.24 g, 1.8 mmol)
and LiAlH4 (1.8 mmol) in ether (7.8 mL) and 26
(655 mg, 1.4 mmol) in 1:1, CH2Cl2–ether (15 mL) at
0 ꢁC as described for 27 to give 28 (430 mg, 66%) as a
light-yellow oil: Rf 0.36 (4:1 hexane–EtOAc); [a]D
+145.4 (c 3.1, CHCl3); 1H NMR (500 MHz, CDCl3)
dH 7.54–7.56 (m, 2H, ArH), 7.33–7.42 (m, 10H, ArH),
7.16 (d, 2H, J = 8.0 Hz, ArH), 5.60 (s, 1H, benzylidene
H), 5.54 (d, 1H, J = 1.0 Hz, H-1), 4.75 (d, 1H,
J = 11.8 Hz, PhCH2), 4.66 (d, 1H, J = 11.8 Hz, PhCH2),
4.35 (ddd, 1H, J = 10.0, 10.0, 5.0 Hz, H-5), 4.25 (dd,
1H, J = 10.0, 5.0 Hz, H-6a), 4.16 (dd, 1H, J = 10.0,
3.5 Hz, H-3), 4.12 (dd, 1H, J = 3.5, 1.0 Hz, H-2), 4.02
(dd, 1H, J = 10.0, 10.0 Hz, H-4), 3.86 (dd, 1H,
J = 10.0, 10.0 Hz, H-6b), 2.54 (br s, 1H, OH), 2.39 (s,
3H, SPhCH3); 13C NMR (125 MHz, CDCl3) dC 138.1

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1755
(Ar), 137.4 (Ar), 137.3 (Ar), 132.5 (2 · Ar), 130.0
(2 · Ar), 129.8 (Ar), 129.2 (Ar), 128.7 (2 · Ar), 128.3
(2 · Ar), 128.2 (Ar), 128.1 (2 · Ar), 126.4 (2 · Ar),
102.2 (benzylidene CH), 86.7 (C-1), 80.1 (C-2), 79.7
(C-4), 73.2 (PhCH2), 69.1 (C-3), 68.5 (C-6), 64.7 (C-5),
21.2 (SPhCH3). Anal. Calcd for C27H28O5S (464.57):
C, 69.80; H, 6.07; S, 6.90. Found: C, 69.60; H, 6.15; S,
6.62. ESIMS: m/z calcd for [C27H28O5S]Na+:
487.1550. Found: 487.1555.
EtOAc); [a]D +33.4 (c 2.5, CHCl3); 1H NMR
(500 MHz, CDCl3) dH 7.48–7.50 (m, 2H, ArH), 7.19–
7.41 (m, 23H, Ar), 5.63 (s, 1H, benzylidene H), 5.52
(dd, 1H, J = 3.2, 1.5 Hz, H-20), 4.93 (d, 1H,
J = 11.0 Hz, PhCH2), 4.91 (d, 1H, J = 1.5 Hz, H-10),
4.82 (d, 1H, J = 2.0 Hz, H-1), 4.75 (s, 2H, PhCH2),
4.66 (d, 1H, J = 12.5 Hz, PhCH2), 4.63 (s, 2H, PhCH2),
4.59 (d, 1H, J = 12.5 Hz, PhCH2), 4.53 (d, 1H,
J = 11.0 Hz, PhCH2), 4.23 (dd, 1H, J = 10.0, 4.5 Hz,
H-6a0), 4.06 (dd, 1H, J = 9.5, 9.5 Hz, H-40), 3.99 (dd,
1H, J = 9.5, 3.2 Hz, H-30), 3.90–3.97 (m, 2H, H-3, H-
50), 3.80–3.90 (m, 3H, H-4, H-6a, H-6b0), 3.79 (dd,
1H, J = 2.5, 2.0 Hz, H-2), 3.69–3.70 (m, 2H, H-5, H-
6b), 3.60 (dt, 1H, J = 10.0, 6.5 Hz, octyl OCH2), 3.34
(dt, 1H, J = 10.0, 6.5 Hz, octyl OCH2), 2.16 (s, 3H,
(CO)CH3), 1.45–1.55 (m, 2H, octyl OCH2CH2), 1.20–
1.35 (m, 10H, octyl CH2), 0.89, (t, 3H, J = 7.5 Hz, octyl
CH3); 13C NMR (125 MHz, CDCl3) dC 170.0 (C@O),
138.7 (Ar), 138.6 (Ar), 138.5 (Ar), 138.1 (Ar), 137.8
(Ar), 128.9 (Ar), 128.5 (Ar), 128.5 (Ar), 128.4 (Ar),
128.2 (Ar), 128.1 (Ar), 128.0 (Ar), 127.9 (Ar), 127.8
(Ar), 127.7 (Ar), 127.7 (Ar), 126.3 (Ar), 101.7 (benzyl-
3.22. Octyl 6-O-(tert-butyldiphenylsilyl)-a-D-manno-
pyranoside (30)
Tetraol 2927 (3.93 g, 13.4 mmol) and imidazole (2.29 g,
33.6 mmol) were dissolved in DMF (15 mL), and tert-
butylchlorodiphenylsilane (4.2 mL, 16.1 mmol) was
added. The reaction mixture was heated at 45 ꢁC for
3 h and was quenched with water (2 mL). The mixture
was then diluted with EtOAc (60 mL), washed with
water (3 · 20 mL), 1 M HCl (20 mL), satd aq NaHCO3
(20 mL), dried (MgSO4), and concentrated to colorless
oil. The crude product was purified by chromatography
(1:1 hexane–EtOAc) to give 30 (6.69 g, 94%) as a color-
less oil: Rf 0.35 (1:1 hexane–EtOAc); [a]D +21.1 (c 7.8,
CHCl3); 1H NMR (400 MHz, CDCl3) dH 7.68–7.71
(m, 4H, ArH), 7.37–7.45 (m, 6H, ArH), 4.77 (d, 1H,
J = 1.6 Hz, H-1), 3.78–3.96 (m, 5H, H-2, H-3, H-4, H-
6a, H-6b), 3.58–3.68 (m, 2H, H-5, octyl OCH2), 3.35
(dt, 1H, J = 9.6, 6.8 Hz, octyl OCH2), 2.06–3.00 (br s,
OH), 1.51–1.56 (m, 2H, octyl OCH2CH2), 1.20–1.37
(m, 10H, octyl CH2), 1.07 (s, 9H, tert-butyl CH3), 0.89
(t, 3H, J = 7.2 Hz, octyl CH3); 13C NMR (100 MHz,
CDCl3) dC 135.6 (4 · Ar), 132.9 (Ar), 132.8 (Ar), 129.9
(2 · Ar), 127.8 (4 · Ar), 99.4 (C-1), 71.8 (C-2), 70.7 (C-
3/C-4/C-5), 70.6 (C-3/C-4/C-5), 70.5 (C-3/C-4/C-5),
67.7 (octyl OCH2), 65.3 (C-6), 31.8 (octyl CH2), 29.4
(octyl CH2), 29.4 (tert-butyl C), 29.2 (octyl CH2), 26.8
(tert-butyl CH3), 26.1 (octyl CH2), 22.6 (octyl CH2),
19.2 (octyl CH2), 14.1 (octyl CH3). ESIMS: m/z calcd
for [C30H46O6Si]Na+: 553.2956. Found: 553.2956.
1
idene CH), 99.1 (C-10, JC,H = 173.5 Hz), 97.8 (C-1,
1JC,H = 167.5 Hz), 80.5 (C-3), 78.5 (C-40), 75.2 (PhCH2),
75.0 (C-2), 74.8 (C-4), 73.9 (C-30), 72.8 (PhCH2), 72.2
(PhCH2), 72.0 (PhCH2), 71.3 (C-5), 69.7 (C-20), 68.9
(C-60), 67.8 (octyl OCH2), 67.3 (C-6), 64.1 (C-50), 32.0
(octyl CH2), 29.5 (octyl CH2), 29.5 (octyl CH2), 29.4
(octyl CH2), 26.3 (octyl CH2), 22.8 (octyl CH2), 21.1
((CO)CH3), 14.1 (octyl CH3). Anal. Calcd for
C57H68O12 (945.14): C, 72.43; H, 7.25. Found: C,
72.72; H, 7.31. ESIMS: m/z calcd for [C57H68O12]Na+:
967.4603. Found: 967.4606.
3.24. Octyl 3-O-acetyl-2-O-benzyl-4,6-O-benzylidene-a-
D-mannopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-manno-
pyranoside (32)
Prepared from thioglycoside 22 (353 mg, 0.70 mmol),
˚
alcohol 23 (299 mg, 0.53 mmol), powdered 4 A molecu-
lar sieves (500 mg), N-iodosuccinimide (190 mg,
0.85 mmol), and AgOTf (41 mg, 0.16 mmol) in CH2Cl2
(20 mL) as described for 31 to give 32 (417 mg, 83%)
as a colorless oil: Rf 0.42 (6:1 hexane–EtOAc); [a]D
3.23. Octyl 2-O-acetyl-3-O-benzyl-4,6-O-benzylidene-a-
D-mannopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-manno-
pyranoside (31)
1
+23.8 (c 1.5, CHCl3); H NMR (500 MHz, CDCl3) dH
Thioglycoside 21 (460 mg, 0.91 mmol), alcohol 23
(378 mg, 0.67 mmol), and powdered 4 A molecular
7.42–7.48 (m, 2H, ArH), 7.22–7.39 (m, 23H, ArH),
5.56 (s, 1H, benzylidene H), 5.33 (dd, 1H, J = 10.0,
3.3 Hz, H-30), 5.14 (d, 1H, J = 1.5 Hz, H-10), 4.98 (d,
1H, J = 11.0 Hz, PhCH2), 4.77 (br s, 1H, H-1), 4.76 (s,
1H, J = 13.0 Hz, PhCH2), 4.63–4.70 (m, 4H, PhCH2),
4.57 (d, 1H, J = 12.0 Hz, PhCH2), 4.44 (d, 1H,
J = 12.0 Hz, PhCH2), 4.26 (dd, 1H, J = 10.0, 5.0 Hz,
H-6a0), 4.15 (dd, 1H, J = 10.0, 10.0 Hz, H-40), 3.76–
4.45 (m, 8H, H-2, H-3, H-4, H-6a, H-6b, H-20, H-50,
H-6b0), 3.73 (m, 1H, H-5), 3.63 (dt, 1H, J = 10.0,
6.8 Hz, octyl OCH2), 3.35 (dt, 1H, J = 10.0, 6.8 Hz,
˚
sieves (350 mg) were dried overnight under vacuum with
P2O5. Dry CH2Cl2 (20 mL) was added, and the reaction
mixture was cooled to 0 ꢁC before the addition of N-iod-
osuccinimide (240 mg, 1.1 mmol) and AgOTf (52 mg,
0.20 mmol). The mixture was stirred for 1 h at 0 ꢁC
and neutralized with Et3N, before being filtered through
Celite and concentrated. The crude residue was purified
by chromatography (4:1 hexane–EtOAc) to give 31
(272 mg, 89%) as a yellow oil: Rf 0.34 (4:1 hexane–

1756
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
octyl OCH2), 2.00 (s, 3H, (CO)CH3), 1.47–1.56 (m, 2H,
octyl OCH2CH2), 1.21–1.35 (m, 10H, octyl CH2), 0.89
(t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz,
CDCl3) dC 170.0 (C@O), 138.5 (Ar), 138.5 (Ar), 138.4
(Ar), 138.0 (Ar), 137.5 (Ar), 128.9 (Ar), 128.4 (Ar),
128.3 (Ar), 128.2 (Ar), 128.1 (Ar), 127.8 (Ar), 127.8
(Ar), 127.8 (Ar), 127.7 (Ar), 127.6 (Ar), 127.6 (Ar),
127.5 (Ar), 126.2 (Ar), 101.7 (benzylidene CH), 98.7
CH2), 14.2 (octyl CH3). Anal. Calcd for C55H66O11
(903.11): C, 73.15; H, 7.37. Found: C, 72.89; H, 7.40.
ESIMS: m/z calcd for [C55H66O11]Na+: 925.4497.
Found: 925.4498.
3.26. Octyl 2-O-benzyl-4,6-O-benzylidene-a-D-manno-
pyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-mannopyran-
oside (34)
1
1
(C-10, JC,H = 175.8 Hz), 97.9 (C-1, JC,H = 175.8 Hz),
80.5 (C-3), 76.8 (C-20), 76.4 (C-40), 75.2 (PhCH2), 75.1
(C-2), 74.8 (C-4), 73.4 (PhCH2), 72.9 (PhCH2), 72.2
(PhCH2), 72.0 (C-5), 70.4 (C-30), 68.9 (C-60), 67.7 (octyl
OCH2), 66.2 (C-6), 64.0 (C-50), 31.9 (octyl CH2), 29.4
(octyl CH2), 29.4 (octyl CH2), 29.2 (octyl CH2), 26.1 (oc-
tyl CH2), 22.7 (octyl CH2), 21.0 ((CO)CH3), 14.1 (octyl
CH3). Anal. Calcd for C57H68O12 (945.14): C, 72.43; H,
7.25. Found: C, 71.96; H, 7.17. ESIMS: m/z calcd for
[C57H68O12]Na+: 967.4603. Found: 967.4605.
Prepared from disaccharide 32 (232 mg, 0.25 mmol) in
CH3OH (15 mL) and NaOCH3 (81 mg) as described
for 33 to give 34 (197 mg, 89%) as a pale-yellow oil: Rf
0.31 (4:1 hexane–EtOAc); [a]D +33.8 (c 3.1, CHCl3); 1H
NMR (500 MHz, CDCl3) dH 7.46–7.54 (m, 2H, ArH),
7.24–7.44 (m, 23H, ArH), 5.58 (s, 1H, benzylidene H),
5.17 (d, 1H, J = 1.0 Hz, H-10), 4.99 (d, 1H,
J = 11.0 Hz, PhCH2), 4.79 (d, 1H, J = 2.0 Hz, H-1),
4.78 (d, 1H, J = 12.0 Hz, PhCH2), 4.63–4.71 (m, 5H,
PhCH2), 4.51 (d, 1H, J = 12.0 Hz, PhCH2), 4.25 (dd,
1H, J = 10.3, 4.3 Hz, H-6a0), 4.10 (dd, 1H, J = 9.4,
3.8 Hz, H-30), 4.00 (dd, 1H, J = 9.4, 9.4 Hz, H-40),
3.86–4.38 (m, 5H, H-3, H-4, H-6a, H-20, H-50), 3.74–
3.86 (m, 3H, H-2, H-6b, H-6b0), 3.72 (m, 1H, H-5),
3.62 (dt, 1H, J = 9.5, 6.5 Hz, octyl OCH2), 3.35 (dt,
1H, J = 9.5, 6.5 Hz, octyl OCH2), 2.28 (br s, 1H, OH),
1.48–1.58 (m, 2H, octyl OCH2CH2), 1.22–1.36 (m, 10H,
octyl CH2), 0.91 (t, 3H, J = 7.0 Hz, octyl CH3); 13C
NMR (125 MHz, CDCl3) dC 138.5 (Ar), 138.4 (Ar),
138.3 (Ar), 137.9 (Ar), 137.5 (Ar), 129.0 (Ar), 128.5
(Ar), 128.4 (Ar), 128.4 (Ar), 128.4 (Ar), 128.2 (Ar),
128.0 (Ar), 127.9 (Ar), 127.9 (Ar), 127.8 (Ar), 127.7
(Ar), 127.7 (Ar), 127.6 (Ar), 127.6 (Ar), 126.4 (Ar),
102.1 (benzylidene CH), 98.4 (C-10), 98.0 (C-1), 80.4
(C-3), 79.6 (C-40), 78.9 (C-20), 75.2 (PhCH2), 75.0 (C-2),
74.6 (C-4), 73.3 (PhCH2), 72.9 (PhCH2), 72.2 (PhCH2),
71.9 (C-5), 68.9 (C-60), 68.6 (C-30), 67.7 (octyl OCH2),
66.4 (C-6), 63.5 (C-50), 31.8 (octyl CH2), 29.4 (octyl
CH2), 29.4 (octyl CH2), 29.2 (octyl CH2), 26.2 (octyl
CH2), 22.7 (octyl CH2), 14.1 (octyl CH3). ESIMS: m/z
calcd for [C55H66O11]Na+: 925.4497. Found: 925.4499.
3.25. Octyl 3-O-benzyl-4,6-O-benzylidene-a-D-manno-
pyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-mannopyran-
oside (33)
Disaccharide 31 (502 mg, 0.53 mmol) was dissolved in
CH3OH (25 mL) and NaOCH3 (140 mg) was added.
After 1 h the solution was neutralized with AcOH, and
the crude product was purified by chromatography
(3:1 hexane–EtOAc) to give 33 (450 mg, 94%) as a color-
less oil: Rf 0.23 (3:1 hexane–EtOAc); [a]D +49.7 (c 2.7,
CHCl3); 1H NMR (500 MHz, CDCl3) dH 7.46–7.52
(m, 2H, ArH), 7.22–7.42 (m, 23H, ArH), 5.61 (s, 1H,
benzylidene H), 5.06 (d, 1H, J = 1.5 Hz, H-10), 4.93 (d,
1H, J = 11.0 Hz, PhCH2), 4.83 (d, 1H, J = 2.0 Hz, H-
1), 4.78 (d, 2H, J = 12.0 Hz, PhCH2), 4.70 (d, 1H,
J = 12.0 Hz, PhCH2), 4.67 (s, 2H, PhCH2), 4.66 (d,
1H, J = 12.0 Hz, PhCH2), 4.56 (d, 1H, J = 11.0 Hz,
PhCH2), 4.25 (dd, 1H, J = 10.0, 4.5 Hz, H-6a0), 4.16
(dd, 1H, J = 3.5, 1.5 Hz, H-20), 4.11 (dd, 1H, J = 9.5,
9.5 Hz, H-40), 3.82–3.97 (m, 6H, H-3, H-4, H-6a, H-30,
H-50, H-6b0), 3.80 (dd, 1H, J = 2.0 Hz, H-2), 3.76 (dd,
2H, J = 11.5, 2.3 Hz, H-6b), 3.68–3.73 (m, 1H, H-5),
3.61 (dt, 1H, J = 10.0, 6.5 Hz, octyl OCH2), 3.35 (dt,
1H, J = 10.0, 6.5 Hz, octyl OCH2), 2.54 (br s, 1H,
OH), 1.47–1.56 (m, 2H, octyl OCH2CH2), 1.22–1.36
(m, 10H, octyl CH2), 0.90 (t, 3H, J = 7.0 Hz, octyl
CH3); 13C NMR (125 MHz, CDCl3) dC 138.7 (Ar),
138.6 (Ar), 138.6 (Ar), 138.2 (Ar), 137.9 (Ar), 129.0
(Ar), 128.6 (Ar), 128.5 (Ar), 128.5 (Ar), 128.5 (Ar),
128.3 (Ar), 128.1 (Ar), 127.9 (Ar), 127.9 (Ar), 127.8
(Ar), 127.7 (Ar), 126.3 (Ar), 101.7 (benzylidene CH),
100.4 (C-10), 97.8 (C-1), 80.3 (C-3), 78.9 (C-40), 75.3
(C-30), 75.2 (PhCH2), 75.1 (C-2), 74.6 (C-4), 72.7
(PhCH2), 72.7 (PhCH2), 72.1 (PhCH2), 71.6 (C-5), 69.8
(C-20), 68.9 (C-60), 67.8 (octyl OCH2), 66.6 (C-6), 63.4
(C-50), 32.0 (octyl CH2), 29.6 (octyl CH2), 29.5 (octyl
CH2), 29.4 (octyl CH2), 26.3 (octyl CH2), 22.8 (octyl
3.27. Octyl 3-O-benzyl-4,6-O-benzylidene-2-O-methyl-a-
D-mannopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-manno-
pyranoside (35)
Disaccharide 33 (270 mg, 0.30 mmol) was dissolved in
DMF (5 mL), and the solution was cooled in an ice bath.
Then 60% NaH in mineral oil (18 mg, 0.45 mmol) was
added, and the mixture was stirred for 10 min before
the addition of CH3I (60 lL, 0.90 mmol). The reaction
mixture was stirred for 1 h and quenched by the addition
of CH3OH (5 mL). The mixture was diluted with EtOAc
(50 mL), washed with water (3 · 15 mL), and dried
(MgSO4), filtered, and concentrated to a colorless oil.
The crude product was purified by chromatography
(4:1 hexane–EtOAc) to give 35 (251 mg, 91%) as a color-

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1757
less oil: Rf 0.32 (4:1 hexane–EtOAc); [a]D +58.5 (c 1.7,
CHCl3); H NMR (500 MHz, CDCl3) dH 7.46–7.51 (m,
(Ar), 137.8 (Ar), 128.8 (Ar), 128.4 (Ar), 128.4 (Ar),
128.4 (Ar), 128.3 (Ar), 128.3 (Ar), 128.1 (Ar), 128.0
(Ar), 127.8 (Ar), 127.7 (Ar), 127.7 (Ar), 127.7 (Ar),
127.7 (Ar), 127.6 (Ar), 127.6 (Ar), 126.3 (Ar), 101.7
(benzylidene CH), 99.3 (C-10), 97.9 (C-1), 80.4 (C-3),
79.0 (C-40), 77.9 (C-30), 76.1 (C-4), 75.1 (PhCH2), 75.0
(C-20), 74.7 (C-2), 73.3 (PhCH2), 72.8 (PhCH2), 72.2
(PhCH2), 71.6 (C-5), 68.9 (C-60), 67.8 (octyl OCH2),
66.5 (C-6), 64.2 (C-50), 58.5 (OCH3), 31.8 (octyl CH2),
29.5 (octyl CH2), 29.4 (octyl CH2), 29.3 (octyl CH2),
26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl CH3).
ESIMS: m/z calcd for [C56H68O11]Na+: 939.4654.
Found: 939.4657.
1
2H, ArH), 7.24–7.42 (m, 22H, ArH), 7.16–7.20 (m, 1H,
ArH), 5.61 (s, 1H, benzylidene H), 5.07 (d, 1H,
J = 1.8 Hz, H-10), 4.89 (d, 1H, J = 10.5 Hz, PhCH2),
4.76–4.82 (m, 3H, H-1, PhCH2), 4.71 (d, 2H,
J = 13.0 Hz, PhCH2), 4.67 (s, 2H, PhCH2), 4.49 (d, 1H,
J = 11.0 Hz, PhCH2), 4.37–4.25 (m, 1H, H-6a0), 4.14
(dd, 1H, J = 9.3, 9.3 Hz, H-40), 3.80–3.95 (m, 6H, H-3,
H-4, H-6a, H-30, H-50, H-6b0), 3.80 (br s, 1H, H-2),
3.74 (dd, 1H, J = 12.0, 1.5 Hz, H-6b), 3.70 (dd, 1H,
J = 3.0, 1.8 Hz, H-20), 3.65–3.72 (m, 1H, H-5), 3.59 (dt,
1H, J = 9.5, 6.8 Hz, octyl OCH2), 3.47 (s, 3H, OCH3),
3.33 (dt, 1H, J = 9.5, 6.8 Hz, octyl OCH2), 1.45–1.55
(m, 2H, octyl OCH2CH2), 1.22–1.36 (m, 10H, octyl
CH2), 0.89 (t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 138.7 (Ar), 138.7 (Ar), 138.6
(Ar), 138.5 (Ar), 138.0 (Ar), 128.9 (Ar), 128.5 (Ar),
128.4 (Ar), 128.3 (Ar), 128.1 (Ar), 128.0 (Ar), 127.9
(Ar), 127.8 (Ar), 127.7 (Ar), 127.6 (Ar), 127.3 (Ar),
101.6 (benzylidene CH), 99.2 (C-10), 98.1 (C-1), 80.5
(C-3), 79.4 (C-20), 79.3 (C-40), 75.5 (C-2/C-30), 75.3 (C-
2/C-30), 75.3 (PhCH2), 74.7 (C-4), 73.1 (PhCH2), 72.9
(PhCH2), 72.4 (PhCH2), 71.9 (C-5), 69.0 (C-60), 67.9
(octyl OCH2), 66.5 (C-6), 64.3 (C-50), 59.9 (OCH3),
32.0 (octyl CH2), 29.8 (octyl CH2), 29.5 (octyl CH2),
29.4 (octyl CH2), 26.3 (octyl CH2), 22.8 (octyl CH2),
14.2 (octyl CH3). Anal. Calcd for C56H68O11 (917.13):
C, 73.34; H, 7.47. Found: C, 73.04; H, 7.44. ESIMS:
m/z calcd for C56H68O11: 939.4654. Found: 939.4656.
3.29. Octyl 3-O-benzyl-4,6-O-benzylidene-2-O-(methyl-
thio)thiocarbonyl-a-D-mannopyranosyl-(1!6)-2,3,4-tri-
O-benzyl-a-D-mannopyranoside (37)
Disaccharide 33 (293 mg, 0.32 mmol) was dissolved in
THF (20 mL), and then 60% NaH in mineral oil
(38 mg, 0.96 mmol) and imidazole (10 mg) were added.
The mixture was stirred for 1 h before the addition of
carbon disulfide (0.19 mL, 3.2 mmol), and stirring was
continued for 1 h. CH3I (0.10 mL, 1.6 mmol) was added,
and the mixture was stirred overnight. The solvent was
evaporated, and the crude product was dissolved in
CH2Cl2 (25 mL), washed with water (10 mL), dried
(MgSO4), and concentrated to a yellow oil. The crude
product was then purified by chromatography (6:1 hex-
ane–EtOAc) to give 37 (310 mg, 96%) as a yellow oil: Rf
0.41 (6:1 hexane–EtOAc); [a]D +24.6 (c 2.6, CHCl3); 1H
NMR (500 MHz, CDCl3) dH 7.47–7.52 (m, 2H, ArH),
7.18–7.42 (m, 23H, ArH), 6.26 (dd, 1H, J = 2.8,
1.5 Hz, H-20), 5.65 (s, 1H, benzylidene H), 5.07 (d, 1H,
J = 1.5 Hz, H-10), 4.93 (d, 1H, J = 11.3 Hz, PhCH2),
4.81 (d, 1H, J = 2.0 Hz, H-1), 4.74 (s, 2H, PhCH2),
4.67 (d, 1H, J = 12.5 Hz, PhCH2), 4.63 (s, 2H, PhCH2),
4.62 (d, 1H, J = 12.5 Hz, PhCH2), 4.55 (d, 1H,
J = 11.3 Hz, PhCH2), 4.26 (dd, 1H, J = 9.8, 4.8 Hz, H-
6a0), 4.08–4.14 (m, 2H, H-30, H-40), 3.94–4.00 (m, 1H,
H-50), 3.91 (dd, 1H, J = 9.0, 3.0 Hz, H-3), 3.82–3.88
(m, 3H, H-4, H-6a, H-6b0), 3.76–3.81 (m, 2H, H-2, H-
6b), 3.72 (ddd, 1H, J = 9.5, 6.0, 1.5 Hz, H-5), 3.60 (dt,
1H, J = 9.5, 6.5 Hz, octyl OCH2), 3.34 (dt, 1H,
J = 9.5, 6.5 Hz, octyl OCH2), 2.61 (s, 3H, SCH3),
1.45–1.55 (m, 2H, octyl OCH2CH2), 1.21–1.35 (m,
10H, octyl CH2), 0.90 (t, 3H, J = 7.0 Hz, octyl CH3);
13C NMR (125 MHz, CDCl3) dC 215.7 (C@S), 138.5
(Ar), 138.4 (Ar), 138.3 (Ar), 137.9 (Ar), 137.6 (Ar),
128.9 (Ar), 128.4 (Ar), 128.4 (Ar), 128.3 (Ar), 128.1
(Ar), 128.0 (Ar), 127.9 (Ar), 127.7 (Ar), 127.7 (Ar),
127.7 (Ar), 127.6 (Ar), 127.6 (Ar), 127.6 (Ar), 126.2
(Ar), 101.7 (benzylidene CH), 97.6 (C-1), 97.6 (C-10),
80.3 (C-3), 78.8 (C-40), 77.9 (C-20), 75.1 (PhCH2), 74.7
(C-2/C-4), 74.8 (C-2/C-4), 73.9 (C-30), 72.7 (PhCH2),
72.1 (PhCH2), 72.0 (PhCH2), 71.0 (C-5), 68.8 (C-60),
3.28. Octyl 2-O-benzyl-4,6-O-benzylidene-3-O-methyl-a-
D-mannopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-manno-
pyranoside (36)
Prepared from disaccharide 34 (197 mg, 0.22 mmol),
60% NaH in mineral oil (13 mg, 0.33 mmol), and
CH3I (42 lL, 0.66 mmol) in DMF (5 mL) as described
for 35 to give 36 (154 mg, 76%) as a colorless oil: Rf
0.38 (6:1 hexane–EtOAc); [a]D +35.6 (c 4.8, CHCl3);
1H NMR (500 MHz, CDCl3) dH 7.46–7.52 (m, 2H,
J = 7.8, 1.8 Hz, ArH), 7.24–7.42 (m, 23H, ArH), 5.62
(s, 1H, benzylidene H), 5.07 (d, 1H, J = 2.0 Hz, H-10),
5.00 (d, 1H, J = 11.0 Hz, PhCH2), 4.81 (d, 1H,
J = 1.5 Hz, H-1), 4.75 (d, 1H, J = 12.5 Hz, PhCH2),
4.72 (d, 1H, J = 12.0 Hz, PhCH2), 4.63–4.71 (m, 5H,
PhCH2), 4.24 (dd, 1H, J = 10.0, 4.5 Hz, H-6a0), 4.16
(dd, 1H, J = 9.5, 9.5 Hz, H-40), 3.90–4.00 (m, 5H, H-3,
H-4, H-6a, H-20, H-50), 3.85 (dd, 1H, J = 10.0,
10.0 Hz, H-6b0), 3.80 (dd, 1H, J = 2.0, 1.8 Hz, H-2),
3.70–3.78 (m, 3H, H-5, H-6b, H-30), 3.63 (dt, 1H,
J = 10.0, 6.8 Hz, octyl OCH2), 3.44 (s, 3H, OCH3),
3.37 (dt, 1H, J = 10.0, 6.8 Hz, octyl OCH2), 1.49–1.58
(m, 2H, octyl OCH2CH2), 1.22–1.36 (m, 10H, octyl
CH2), 0.91 (t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 138.5 (Ar), 138.4 (Ar), 138.3

1758
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
67.7 (octyl OCH2), 66.9 (C-6), 63.9 (C-50), 31.9 (octyl
CH2), 29.5 (octyl CH2), 29.4 (octyl CH2), 29.3 (octyl
CH2), 26.2 (octyl CH2), 22.7 (octyl CH2), 19.2 (SCH3),
14.1 (octyl CH3). ESIMS: m/z calcd for [C57H68O11S2]-
Na+: 1015.4095. Found: 1015.4096.
CH3I (0.15 mL, 2.4 mmol) in THF (13 mL) as described
for 37 to give 39 (227 mg, 94%) as a colorless oil: Rf 0.31
(6:1 hexane–EtOAc); [a]D +5.2 (c 0.7, CHCl3); 1H NMR
(500 MHz, CDCl3) dH 7.44–7.50 (m, 2H, ArH), 7.21–
7.40 (m, 23H, ArH), 6.15 (dd, 1H, J = 10.0, 3.5 Hz,
H-30), 5.61 (s, 1H, benzylidene H), 5.14 (d, 1H,
J = 1.5 Hz, H-10), 4.99 (d, 1H, J = 11.0 Hz, PhCH2),
4.77 (d, 1H, J = 1.5 Hz, H-1), 4.76 (d, 1H,
J = 12.0 Hz, PhCH2), 4.64–4.70 (m, 4H, PhCH2), 4.51
(d, 1H, J = 11.5 Hz, PhCH2), 4.48 (d, 1H, J = 12.0 Hz,
PhCH2), 4.40 (dd, 1H, J = 10.0, 10.0 Hz, H-40), 4.36
(dd, 1H, J = 3.5, 1.5 Hz, H-20), 4.29 (dd, 1H, J = 10.5,
5.0 Hz, H-6a0), 4.09 (ddd, 1H, J = 10.0, 10.0, 5.0 Hz,
H-50), 3.99 (dd, 1H, J = 9.5, 9.5 Hz, H-6a), 3.85–4.02
(m, 3H, H-3, H-4, H-6b0), 3.72–3.81 (m, 3H, H-2, H-5,
H-6b), 3.65 (dt, 1H, J = 9.8, 6.5 Hz, octyl OCH2), 3.35
(dt, 1H, J = 9.8, 6.5 Hz, octyl OCH2), 2.55 (s, 3H,
SCH3), 1.46–1.58 (m, 2H, octyl OCH2CH2), 1.22–1.36
(m, 10H, octyl CH2), 0.90 (t, 3H, J = 7.0 Hz, octyl
CH3); 13C NMR (125 MHz, CDCl3) dC 215.0 (C@S),
138.6 (Ar), 138.5 (Ar), 138.4 (Ar), 137.9 (Ar), 137.4
(Ar), 128.9 (Ar), 128.4 (Ar), 128.3 (Ar), 128.2 (Ar),
128.1 (Ar), 127.9 (Ar), 127.7 (Ar), 127.7 (Ar), 127.6
(Ar), 127.5 (Ar), 126.2 (Ar), 101.6 (benzylidene CH),
99.2 (C-10), 97.9 (C-1), 80.5 (C-3), 79.1 (C-30), 76.3 (C-
40), 75.8 (C-20), 75.3 (PhCH2), 75.1 (C-2), 74.9 (C-4),
73.6 (PhCH2), 73.0 (PhCH2), 72.2 (PhCH2), 72.0 (C-5),
68.9 (C-60), 67.6 (octyl OCH2), 66.4 (C-6), 64.1 (C-50),
31.9 (octyl CH2), 29.5 (octyl CH2), 29.5 (octyl CH2),
29.3 (octyl CH2), 26.3 (octyl CH2), 22.7 (octyl CH2),
19.1 (SCH3), 14.1 (octyl CH3). Anal. Calcd for
C57H68O11S2 (993.27): C, 68.92; H, 6.90; S, 6.46. Found:
C, 68.41; H, 6.86; S, 6.18. ESIMS: m/z calcd for
[C57H68O11S2]Na+: 1015.4095. Found: 1015.4094.
3.30. Octyl 3-O-benzyl-4,6-O-benzylidene-2-deoxy-a-D-
arabino-hexopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-
mannopyranoside (38)
Xanthate 37 (310 mg, 0.31 mmol) was dissolved in
toluene (15 mL), and tri-n-butylstannane (1.3 mL,
0.47 mmol) and AIBN (51 mg, 0.31 mmol) were added.
The mixture was heated at reflux for 3 h, and the solvent
was evaporated. The crude product was purified by chro-
matography (4:1 hexane–EtOAc) to give 38 (113 mg,
41%) as a colorless oil: Rf 0.42 (4:1 hexane–EtOAc);
[a]D +50.8 (c 3.3, CHCl3); 1H NMR (500 MHz, CDCl3)
dH 7.46–7.54 (m, 2H, ArH), 7.20–7.42 (m, 23H, ArH),
5.62 (s, 1H, benzylidene H), 5.08 (br d, 1H, J = 3.5 Hz,
H-10), 4.95 (d, 1H, J = 11.0 Hz, PhCH2), 4.83 (d, 1H,
J = 1.5 Hz, H-1), 4.80 (d, 1H, J = 12.0 Hz, PhCH2),
4.78 (d, 1H, J = 12.5 Hz, PhCH2), 4.70 (d, 1H,
J = 12.5 Hz, PhCH2), 4.63–4.68 (m, 3H, PhCH2), 4.60
(d, 1H, J = 11.0 Hz, PhCH2), 4.23 (dd, 1H, J = 10.0,
5.0 Hz, H-6a0), 4.03 (ddd, 1H, J = 11.0, 11.0, 5.0 Hz,
H-30), 3.84–3.98 (m, 4H, H-3, H-4, H-6a, H-50), 3.66–
3.82 (m, 5H, H-2, H-5, H-6b, H-40, H-6b0), 3.63 (dt,
1H, J = 9.5, 6.5 Hz, octyl OCH2), 3.36 (dt, 1H, J = 9.5,
6.5 Hz, octyl OCH2), 2.35 (dd, 1H, J = 13.3, 5.0 Hz,
H-20eq), 1.78 (ddd, 1H, J = 13.3, 11.0, 3.5 Hz, H-2a0 x),
1.47–1.56 (m, 2H, octyl OCH2CH2), 1.22–1.35 (m,
10H, octyl CH2), 0.90 (t, 3H, J = 7.3 Hz, octyl CH3);
13C NMR (125 MHz, CDCl3) dC 138.7 (Ar), 138.5
(Ar), 138.5 (Ar), 138.4 (Ar), 137.8 (Ar), 128.8 (Ar),
128.5 (Ar), 128.4 (Ar), 128.4 (Ar), 128.3 (Ar), 128.3
(Ar), 128.2 (Ar), 127.9 (Ar), 127.7 (Ar), 127.7 (Ar),
127.7 (Ar), 127.6 (Ar), 127.6 (Ar), 127.5 (Ar), 127.5
(Ar), 126.1 (Ar), 101.4 (benzylidene CH), 98.1 (C-10),
97.7 (C-1), 84.0 (C-40), 80.4 (C-3), 75.2 (PhCH2), 75.0
(C-2), 74.9 (C-4), 72.8 (C-30), 72.8 (PhCH2), 72.7
(PhCH2), 72.1 (PhCH2), 71.5 (C-5), 69.2 (C-60), 67.7 (oc-
tyl OCH2), 66.1 (C-6), 63.1 (C-50), 36.4 (C-20), 31.9 (octyl
CH2), 29.4 (octyl CH2), 29.4 (octyl CH2), 29.3 (octyl
CH2), 26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl
CH3). Anal. Calcd for C55H66O10 (887.11): C, 74.47; H,
7.50. Found: C, 74.10; H, 7.89. ESIMS: m/z calcd for
[C55H66O10]Na+: 909.4548. Found: 909.4551.
3.32. Octyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-a-D-
arabino-hexopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-
mannopyranoside (40)
Xanthate 39 (206 mg, 0.21 mmol) was dissolved in tolu-
ene (10 mL) and added dropwise to a solution of tri-n-
butylstannane (85 lL, 0.32 mmol) and AIBN (10 mg,
0.063 mmol) in toluene (15 mL) at reflux, over a period
of 1 h. The mixture was heated under reflux for 1 h, tri-
n-butylstannane (85 lL, 0.32 mmol) and AIBN (10 mg,
0.063 mmol) in toluene (5 mL) were added, and the reac-
tion mixture was continually heated under reflux for 1 h.
The solvent was evaporated, and the crude product was
purified by chromatography (6:1 hexane–EtOAc) to give
40 (69 mg, 37%) as a colorless oil: Rf 0.41 (6:1 hexane–
EtOAc); [a]D +52.1 (c 1.3, CHCl3); 1H NMR
(500 MHz, CDCl3) dH 7.45–7.50 (m, 2H, ArH), 7.23–
7.39 (m, 23H, AHr), 5.57 (s, 1H, benzylidene H), 4.99
(br s, 1H, H-10), 4.98 (d, 1H, J = 11.0 Hz, PhCH2),
4.79 (d, 1H, J = 1.5 Hz, H-1), 4.76 (d, 1H, J = 12.0 Hz,
PhCH2), 4.64–4.69 ( m, 4H, PhCH2), 4.52 (s, 2H,
3.31. Octyl 2-O-benzyl-4,6-O-benzylidene-3-O-(methyl-
thio)thiocarbonyl-a-D-mannopyranosyl-(1!6)-2,3,4-tri-
O-benzyl-a-D-mannopyranoside (39)
Prepared from disaccharide 34 (219 mg, 0.24 mmol),
60% NaH in mineral oil (29 mg, 0.72 mmol), imidazole
(10 mg), carbon disulfide (0.15 mL, 2.4 mmol), and

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1759
PhCH2), 4.21 (dd, 1H, J = 5.3, 4.8 Hz, H-6a0), 3.92–4.04
(m, 5H, H-3, H-4, H-6a, H-40, H-50), 3.76–3.83 (m, 4H,
H-2, H-6b, H-20, H-6b0), 3.70–3.75 (m, 1H, H-5), 3.62
(dt, 1H, J = 9.5, 6.8 Hz, octyl OCH2), 3.35 (dt, 1H,
J = 9.5, 6.8 Hz, octyl OCH2), 2.19 (ddd, 1H, J = 12.5,
3.5, 3.5 Hz, H-30eq), 2.01 (ddd, 1H, J = 12.5, 12.5,
(octyl OCH2), 66.4 (C-6), 64.3 (C-50), 31.8 (octyl CH2),
29.4 (octyl CH2), 29.4 (octyl CH2), 29.2 (octyl CH2),
26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl CH3).
Anal. Calcd for C62H72O11 (993.23): C, 74.97; H, 7.31.
Found: C, 74.63; H, 7.54. ESIMS: m/z calcd for
[C62H72O11]Na+: 1015.4967. Found: 1015.4963.
3.0 Hz, H-30 ), 1.47–1.56 (m, 2H, octyl OCH2CH2),
ax
1.22–1.35 (m, 10H, octyl CH2), 0.89 (t, 3H, J = 7.0 Hz,
octyl CH3); 13C NMR (125 MHz, CDCl3) dC 138.5
(Ar), 138.5 (Ar), 138.4 (Ar), 138.2 (Ar), 137.8 (Ar),
128.9 (Ar), 128.4 (Ar), 128.4 (Ar), 128.4 (Ar), 128.3
(Ar), 128.3 (Ar), 128.0 (Ar), 127.8 (Ar), 127.7 (Ar),
127.6 (Ar), 127.6 (Ar), 127.6 (Ar), 126.2 (Ar), 102.0 (ben-
zylidene CH), 97.9 (C-10), 97.9 (C-1), 80.4 (C-3), 75.5 (C-
2/C-20), 75.2 (PhCH2), 75.0 (C-2/C-20), 74.7 (C-4/C-40),
74.3 (C-4/C-40), 72.8 (PhCH2), 72.2 (PhCH2), 71.8 (C-
5), 71.3 (PhCH2), 69.4 (C-60), 67.7 (octyl OCH2), 66.4
(C-6), 65.2 (C-50), 31.8 (octyl CH2), 29.5 (octyl CH2),
29.4 (C-30), 29.4 (octyl CH2), 29.2 (octyl CH2), 26.2 (oc-
tyl CH2), 22.7 (octyl CH2), 14.1 (octyl CH3). Anal. Calcd
for C55H66O10 (887.11): C, 74.47; H, 7.50. Found: C,
74.39; H, 7.55. ESIMS: m/z calcd for [C55H66O10]Na+:
909.4548. Found: 909.4551.
3.34. Octyl 2,3,6-tri-O-benzyl-a-D-mannopyranosyl-
(1!6)-2,3,4-tri-O-benzyl-a-D-mannopyranoside (42)
A solution of disaccharide 41 (450 mg, 0.45 mmol) and
˚
powdered 4 A molecular sieves (1.8 g) in CH2Cl2
(6 mL) was stirred at room temperature for 1 h. The
solution was cooled to ꢀ78 ꢁC, followed by the addition
of Et3SiH (0.22 mL, 1.4 mmol) and TfOH (0.14 mL,
1.5 mmol). After 1 h the reaction was quenched with
Et3N and CH3OH, diluted with CH2Cl2, washed with
satd aq NaHCO3, dried (MgSO4), and concentrated.
The crude product was purified by chromatography
(4:1 hexane–EtOAc) to give 42 (276 mg, 61%) and 43
(17 mg, 4%) as colorless oils: Rf 0.33 (4:1 hexane–
EtOAc); [a]D +7.9 (c 1.2, CHCl3); 1H NMR
(500 MHz, CDCl3) dH 7.18–7.42 (m, 30H, ArH), 5.16
(d, 1H, J = 1.5 Hz, H-10), 4.91 (d, 1H, J = 11.0 Hz,
PhCH2), 4.81 (d, 1H, J = 1.8 Hz, H-1), 4.75 (d, 1H,
J = 12.0 Hz, PhCH2), 4.64–4.71 (m, 4H, PhCH2), 4.61
(d, 1H, J = 12.5 Hz, PhCH2), 4.60 (d, 1H, J = 12.0 Hz,
PhCH2), 4.55 (d, 2H, J = 11.5 Hz, PhCH2), 4.51 (d,
1H, J = 11.0 Hz, PhCH2), 4.40 (d, 1H, J = 12.0 Hz,
PhCH2), 4.07 (ddd, 1H, J = 10.0, 10.0, 1.3 Hz, H-40),
3.91–4.00 (m, 4H, H-3, H-4, H-6a, H-20), 3.81 (dd,
1H, J = 3.0, 1.8 Hz, H-2), 3.67–3.81 (m, 6H, H-5, H-
6b, H-30, H-50, H-6a0, H-6b0), 3.60 (dt, 1H, J = 9.5,
6.5 Hz, octyl OCH2), 3.34 (dt, 1H, J = 9.5, 6.5 Hz, octyl
OCH2), 2.43 (d, 1H, J = 1.3 Hz, OH), 1.47–1.56 (m, 2H,
octyl OCH2CH2), 1.22–1.36 (m, 10H, octyl CH2), 0.89
(t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR (100 MHz,
CDCl3) dC 138.5 (Ar), 138.5 (Ar), 138.4 (Ar), 138.3
(Ar), 138.1 (Ar), 128.5 (Ar), 128.4 (Ar), 128.3 (Ar),
128.3 (Ar), 128.2 (Ar), 128.0 (Ar), 127.8 (Ar), 127.8
(Ar), 127.7 (Ar), 127.7 (Ar), 127.6 (Ar), 127.4 (Ar),
127.4 (Ar), 98.4 (C-10), 97.9 (C-1), 80.4 (C-3), 78.7 (C-
30), 75.2 (C-2), 75.1 (PhCH2), 75.1 (C-20), 74.2 (C-4),
73.5 (PhCH2), 72.9 (PhCH2), 72.4 (PhCH2), 72.2
(PhCH2), 71.7 (C-5), 71.5 (C-50), 71.1 (PhCH2), 70.4
(C-60), 67.7 (C-40), 67.7 (octyl OCH2), 66.2 (C-6), 31.8
(octyl CH2), 29.4 (octyl CH2), 29.4 (octyl CH2), 29.2 (oc-
tyl CH2), 26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl
CH3). ESIMS: m/z calcd for [C62H74O11]Na+:
1017.5123. Found: 1017.5128.
3.33. Octyl 2,3-di-O-benzyl-4,6-O-benzylidene-a-D-
mannopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-manno-
pyranoside (41)
Prepared from disaccharide 33 (1.57 g, 1.6 mmol), 60%
NaH in mineral oil (0.10 g, 2.6 mmol), and BnBr
(0.32 mL, 2.6 mmol) in DMF (15 mL) as described for
23 to give 41 (1.62 g, 94%) as a colorless oil: Rf 0.28 (9:1
1
hexane–EtOAc); [a]D +35.6 (c 2.3, CHCl3); H NMR
(600 MHz, CDCl3) dH 7.48–7.52 (m, 2H, ArH), 7.18–
7.40 (m, 28H, ArH), 5.64 (s, 1H, benzylidene H), 5.09
(br s, 1H, H-10), 4.90 (d, 1H, J = 11.4 Hz, PhCH2), 4.80
(d, 1H, J = 1.8 Hz, H-1), 4.75 (d, 1H, J = 12.6 Hz,
PhCH2), 4.74 (d, 1H, J = 12.6 Hz, PhCH2), 4.63–4.72
(m, 5H, PhCH2), 4.63 (d, 1H, J = 12.0 Hz, PhCH2),
4.52 (d, 1H, J = 10.8 Hz, PhCH2), 4.20–4.27 (m, 2H, H-
40, H-6a0), 3.90–3.98 (m, 2H, H-20, H-30), 3.84–3.95 (m,
5H, H-3, H-4, H-6a, H-50, H-6b0), 3.79 (dd, 1H, J = 1.8,
1.8 Hz, H-2), 3.73 (dd, 1H, J = 11.7, 1.5 Hz, H-6b),
3.66–3.71 (m, 1H, H-5), 3.59 (dt, 1H, J = 9.6, 6.6 Hz, oc-
tyl OCH2), 3.34 (dt, 1H, J = 9.6, 6.6 Hz, octyl OCH2),
1.46–1.54 (m, 2H, octyl OCH2CH2), 1.22–1.34 (m, 10H,
octyl CH2), 0.90 (t, 3H, J = 7.2 Hz, octyl CH3); 13C
NMR (125 MHz, CDCl3) dC 138.6 (Ar), 138.5 (Ar),
138.5 (Ar), 138.4 (Ar), 138.3 (Ar), 137.9 (Ar), 128.7
(Ar), 128.4 (Ar), 128.4 (Ar), 128.3 (Ar), 128.3 (Ar),
128.1 (Ar), 128.0 (Ar), 127.8 (Ar), 127.8 (Ar), 127.7
(Ar), 127.7 (Ar), 127.6 (Ar), 127.5 (Ar), 127.4 (Ar),
101.5 (benzylidene CH), 99.5 (C-10), 97.8 (C-1), 80.4 (C-
3), 79.1 (C-40), 76.9 (C-30), 75.8 (C-20), 75.2 (PhCH2),
75.0 (C-2), 74.6 (C-4), 73.4 (PhCH2), 72.8 (PhCH2), 72.6
(PhCH2), 72.2 (PhCH2), 71.7 (C-5), 68.9 (C-60), 67.7
3.35. Octyl 2,3,4-tri-O-benzyl-a-D-mannopyranosyl-
(1!6)-2,3,4-tri-O-benzyl-a-D-mannopyranoside (43)
Prepared from a solution of AlCl3 (62 mg, 0.46 mmol) and
LiAlH4 (0.46 mmol) in ether (3.5 mL) and disaccharide

1760
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
41 (382 mg, 0.39 mmol) in 1:1 CH2Cl2–ether (15 mL)
as described for 27 (except that the reaction mixture
was stirred overnight), to give 43 (324 mg, 85%)
and 42 (11 mg, 3%) as colorless oils: Rf 0.24 (3:1
CH2), 0.89 (t, 3H, J = 7.2 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 138.8 (Ar), 138.6 (Ar), 138.6
(Ar), 138.5 (Ar), 138.4 (Ar), 128.3 (Ar), 128.3 (Ar),
128.3 (Ar), 128.2 (Ar), 128.2 (Ar), 127.9 (Ar), 127.8
(Ar), 127.6 (Ar), 127.6 (Ar), 127.6 (Ar), 127.6 (Ar),
127.5 (Ar), 127.4 (Ar), 127.3 (Ar), 98.1 (C-10), 97.8
(C-1), 80.4 (C-3), 79.4 (C-30), 76.5 (C-40), 75.1 (C-2),
75.1 (C-20), 75.1 (PhCH2), 74.7 (C-4), 73.3 (PhCH2),
72.8 (PhCH2), 72.4 (PhCH2), 72.2 (PhCH2), 71.9 (C-
50), 71.7 (C-5), 71.6 (PhCH2), 69.4 (C-60), 67.6 (octyl
OCH2), 66.1 (C-6), 60.6 (OCH3), 31.8 (octyl CH2),
29.4 (octyl CH2), 29.4 (octyl CH2), 29.2 (octyl CH2),
26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl CH3).
ESIMS: m/z calcd for [C63H76O11]Na+: 1031.5280.
Found: 1031.5280.
1
hexane–EtOAc); [a]D +33.5 (c 1.2, CHCl3); H NMR
(500 MHz, CDCl3) dH 7.18–7.40 (m, 30H, ArH), 5.09
(br s, 1H, H-10), 4.94 (d, 1H, J = 11.0 Hz, PhCH2),
4.91 (d, 1H, J = 11.0 Hz, PhCH2), 4.80 (d, 1H,
J = 1.5 Hz, H-1), 4.47–4.77 (m, 10H, PhCH2), 3.87–
4.00 (m, 6H, H-3, H-4, H-6a, H-20, H-30, H-40), 3.64–
3.81 (m, 6H, H-2, H-5, H-6b, H-50, H-6a0, H-6b0), 3.59
(dt, 1H, J = 9.7, 6.4 Hz, octyl OCH2), 3.33 (dt, 1H,
J = 9.7, 6.4 Hz, octyl OCH2), 1.78 (br s, 1H, OH),
1.45–1.55 (m, 2H, octyl OCH2CH2), 1.21–1.35 (m,
10H, octyl CH2), 0.89 (t, 3H, J = 7.0 Hz, octyl CH3);
13C NMR (100 MHz, CDCl3) dC 138.6 (Ar), 138.6
(Ar), 138.5 (Ar), 138.5 (Ar), 138.3 (Ar), 128.8 (Ar),
128.8 (Ar), 128.6 (Ar), 128.6 (Ar), 128.5 (Ar), 128.5
(Ar), 128.5 (Ar), 128.3 (Ar), 128.3 (Ar), 128.3 (Ar),
127.9 (Ar), 127.8 (Ar), 127.8 (Ar), 127.7 (Ar), 127.6
(Ar), 127.6 (Ar), 127.5 (Ar), 127.5 (Ar), 127.5 (Ar),
127.5 (Ar), 98.3 (C-10), 97.8 (C-1), 80.4 (C-3), 79.4 (C-
30), 79.4 (C-40), 75.1 (C-2), 75.1 (PhCH2), 74.7 (C-20),
74.6 (C-4), 72.8 (PhCH2), 72.7 (PhCH2), 72.7 (PhCH2),
72.2 (C-50), 72.1 (PhCH2), 71.6 (PhCH2), 71.6 (C-5),
67.7 (octyl OCH2), 66.1 (C-6), 62.3 (C-60), 31.8 (octyl
CH2), 29.4 (octyl CH2), 29.4 (octyl CH2), 29.2
(octyl CH2), 26.2 (octyl CH2), 22.6 (octyl CH2), 14.1
(octyl CH3). ESIMS: m/z calcd for [C62H74O11]Na+:
1017.5123. Found: 1017.5136.
3.37. Octyl 2,3,6-tri-O-benzyl-4-O-(methylthio)thiocar-
bonyl-a-D-mannopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-
D-mannopyranoside (45)
Prepared from disaccharide 42 (148 mg, 0.15 mmol),
60% NaH in mineral oil (18 mg, 0.45 mmol), carbon
disulfide (0.092 mL, 1.5 mmol), and CH3I (0.094 mL,
1.5 mmol) in THF (9 mL) as described for 37 to give
45 (154 mg, 96%) as a light-yellow oil: Rf 0.37 (6:1 hex-
ane–EtOAc); [a]D +34.1 (c 0.7, CHCl3); 1H NMR
(500 MHz, CDCl3) dH 7.16–7.42 (m, 30H, ArH), 6.36
(dd, 1H, J = 9.5, 9.5 Hz, H-40), 5.14 (br s, 1H, H-10),
4.88 (d, 1H, J = 11.0 Hz, PhCH2), 4.81 (d, 1H,
J = 1.9 Hz, H-1), 4.63–4.77 (m, 6H, PhCH2), 4.53 (d,
1H, J = 12.5 Hz, PhCH2), 4.49 (s, 2H, PhCH2), 4.45
(d, 1H, J = 11.5 Hz, PhCH2), 4.42 (d, 1H,
J = 12.0 Hz, PhCH2), 3.91–4.01 (m, 6H, H-3, H-4, H-
6a, H-20, H-30, H-50), 3.81 (dd, 1H, J = 1.9, 1.9 Hz,
H-2), 3.72 (dd, 1H, J = 11.8, 1.3 Hz, H-6b), 3.66–3.71
(m, 1H, H-5), 3.54–3.63 (m, 3H, H-6a0, H-6b0, octyl
OCH2), 3.34 (dt, 1H, J = 9.5, 6.5 Hz, octyl OCH2),
2.48 (s, 3H, SCH3), 1.48–1.56 (m, 2H, octyl OCH2CH2),
1.22–1.36 (m, 10H, octyl CH2), 0.90 (t, 3H, J = 7.0 Hz,
octyl CH3); 13C NMR (125 MHz, CDCl3) dC 215.4
(C@S), 138.6 (Ar), 138.6 (Ar), 138.5 (Ar), 138.3 (Ar),
138.3 (Ar), 138.0 (Ar), 128.4 (Ar), 128.2 (Ar), 128.1
(Ar), 127.9 (Ar), 127.8 (Ar), 127.8 (Ar), 127.7 (Ar),
127.6 (Ar), 127.6 (Ar), 127.6 (Ar), 127.5 (Ar), 127.5
(Ar), 127.3 (Ar), 127.3 (Ar), 98.7 (C-10), 97.8 (C-1),
80.4 (C-3), 77.7 (C-40), 76.4 (C-30), 75.2 (C-2), 75.1
(PhCH2), 75.0 (C-20), 74.5 (C-4), 73.4 (PhCH2), 72.9
(PhCH2), 72.8 (PhCH2), 72.2 (PhCH2), 71.6 (C-5),
71.3 (PhCH2), 70.5 (C-50), 69.7 (C-60), 67.7 (octyl
OCH2), 66.5 (C-6), 31.9 (octyl CH2), 29.4 (octyl CH2),
29.4 (octyl CH2), 29.2 (octyl CH2), 26.2 (octyl CH2),
22.7 (octyl CH2), 19.2 (SCH3), 14.1 (octyl CH3). Anal.
Calcd for C64H76O11S2 (1084.48): C, 70.82; H, 7.06; S,
5.91. Found: C, 71.04; H, 6.91; S, 5.93. ESIMS: m/z
calcd for [C64H76O11S2]Na+: 1107.4721. Found:
1107.4725.
3.36. Octyl 2,3,6-tri-O-benzyl-4-O-methyl-a-D-manno-
pyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-mannopyran-
oside (44)
Prepared from disaccharide 42 (134 mg, 0.14 mmol),
60% NaH in mineral oil (8.1 mg, 0.20 mmol), and
CH3I (13 lL, 0.20 mmol) in DMF (3 mL) as described
for 35 to give 44 (105 mg, 77%) as a colorless oil: Rf
0.22 (4:1 hexane–EtOAc); [a]D +30.3 (c 1.5, CHCl3);
1H NMR (600 MHz, CDCl3) dH 7.19–7.40 (m, 30H,
ArH), 5.12 (d, 1H, J = 2.1 Hz, H-10), 4.89 (d, 1H,
J = 10.8 Hz, PhCH2), 4.78 (d, 1H, J = 2.1 Hz, H-1),
4.73 (d, 1H, J = 12.6 Hz, PhCH2), 4.69 (d, 1H,
J = 12.0 Hz, PhCH2), 4.67 (d, 1H, J = 12.6 Hz,
PhCH2), 4.65 (s, 2H, PhCH2), 4.65 (s, 2H, PhCH2),
4.57 (d, 1H, J = 12.0 Hz, PhCH2), 4.54 (d, 1H,
J = 12.0 Hz, PhCH2), 4.52 (d, 1H, J = 12.0 Hz,
PhCH2), 4.51 (d, 1H, J = 10.8 Hz, PhCH2), 3.90–3.96
(m, 3H, H-3, H-4, H-6a), 3.90 (dd, 1H, J = 3.6,
2.1 Hz, H-20), 3.81 (dd, 1H, J = 7.8, 3.6 Hz, H-30),
3.78 (dd, 1H, J = 2.1, 2.1 Hz, H-2), 3.64–3.76 (m, 6H,
H-5, H-6b, H-40, H-50, H-6a0, H-6b0), 3.58 (dt, 1H,
J = 9.6, 6.6 Hz, octyl OCH2), 3.49 (s, 3H, OCH3),
3.32 (dt, 1H, J = 9.6, 6.6 Hz, octyl OCH2), 1.46–1.54
(m, 2H, octyl OCH2CH2), 1.22–1.34 (m, 10H, octyl

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1761
3.38. Octyl 2,3,6-tri-O-benzyl-4-deoxy-a-D-lyxo-hexo-
pyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-mannopyran-
oside (46)
PhCH2), 3.89–3.99 (m, 6H, H-3, H-4, H-6a, H-20, H-
30, H-40), 3.66–3.81 (m, 4H, H-2, H-5, H-6b, H-50),
3.51–3.62 (m, 3H, H-6a0, H-6b0, octyl OCH2), 3.30–
3.37 (m, 4H, OCH3, octyl OCH2), 1.46–1.55 (m, 2H, oct-
yl OCH2CH2), 1.21–1.35 (m, 10H, octyl CH2), 0.90 (t,
3H, J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz,
CDCl3) dC 138.9 (Ar), 138.7 (Ar), 138.6 (Ar), 138.5
(Ar), 138.5 (Ar), 138.4 (Ar), 128.4 (Ar), 128.3 (Ar),
128.3 (Ar), 128.3 (Ar), 128.3 (Ar), 128.2 (Ar), 127.8
(Ar), 127.8 (Ar), 127.7 (Ar), 127.7 (Ar), 127.6 (Ar),
127.6 (Ar), 127.5 (Ar), 127.4 (Ar), 127.3 (Ar), 98.3 (C-
10), 97.8 (C-1), 80.5 (C-3), 79.5 (C-30), 75.1 (C-2), 75.1
(PhCH2), 75.0 (PhCH2), 75.0 (C-20), 74.9 (C-4), 74.6
(C-40), 72.8 (PhCH2), 72.4 (PhCH2), 72.2 (PhCH2),
71.7 (C-60), 71.6 (C-5), 71.5 (C-50), 71.5 (PhCH2), 67.6
(octyl OCH2), 66.1 (C-6), 59.1 (OCH3), 31.8 (octyl
CH2), 29.4 (octyl CH2), 29.4 (octyl CH2), 29.2
(octyl CH2), 26.1 (octyl CH2), 22.7 (octyl CH2), 14.1
(octyl CH3). Anal. Calcd for C63H76O11 (1008.54): C,
74.97; H, 7.59. Found: C, 74.30; H, 7.71. ESIMS: m/z
calcd for [C63H76O11]Na+: 1031.5280. Found:
1031.5282.
Prepared from xanthate 45 (129 mg, 0.12 mmol) in tolu-
ene (2 mL) and tri-n-butylstannane (50 lL, 0.18 mmol)
and AIBN (6 mg, 0.037 mmol) as described for 40 to
give 46 (76 mg, 64%) as a colorless oil: Rf 0.31 (6:1 hex-
ane–EtOAc); [a]D +20.8 (c 0.6, CHCl3); 1H NMR
(600 MHz, CDCl3) dH 7.18–7.41 (m, 30H, ArH), 5.15
(d, 1H, J = 1.2 Hz, H-10), 4.89 (d, 1H, J = 12.0 Hz,
PhCH2), 4.81 (d, 1H, J = 1.8 Hz, H-1), 4.75 (d, 1H,
J = 12.6 Hz, PhCH2), 4.74 (d, 1H, J = 12.6 Hz, PhCH2),
4.70 (d, 1H, J = 12.6 Hz, PhCH2), 4.70 (d, 1H,
J = 12.6 Hz, PhCH2), 4.69 (s, 2H, PhCH2), 4.54 (s,
2H, PhCH2), 4.49 (d, 2H, J = 12.0 Hz, PhCH2), 4.45
(d, 1H, J = 12.0 Hz, PhCH2), 3.91 (m, 4H, H-3, H-4,
H-6a, H-50), 3.84–3.91 (m, 2H, H-20, H-30), 3.80 (dd,
1H, J = 2.4, 1.8 Hz, H-2), 3.72 (dd, 1H, J = 12.0,
1.8 Hz, H-6b), 3.68–3.72 (m, 1H, H-5), 3.59 (dt, 1H,
J = 9.6, 6.6 Hz, octyl OCH2), 3.56 (dd, 1H, J = 10.2,
6.0 Hz, H-6a0), 3.45 (dd, 1H, J = 10.2, 4.2 Hz, H-6b0),
3.33 (dt, 1H, J = 9.6, 6.6 Hz, octyl OCH2), 1.98 (ddd,
1H, J = 12.0, 12.0, 12.0 Hz, H-40ax), 1.73–1.78 (m, 1H,
3.40. Octyl 2,3,4-tri-O-benzyl-6-O-p-tolylsulfonyl-a-D-
mannopyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-manno-
pyranoside (48)
H-40 ), 1.47–1.55 (m, 2H, octyl OCH2CH2), 1.21–1.35
eq
(m, 10H, octyl CH2), 0.90 (t, 3H, J = 7.2 Hz, octyl
CH3); 13C NMR (125 MHz, CDCl3) dC 139.0 (Ar),
138.6 (Ar), 138.6 (Ar), 138.5 (Ar), 138.4 (Ar), 138.4
(Ar), 128.3 (Ar), 128.3 (Ar), 128.3 (Ar), 128.2 (Ar),
127.8 (Ar), 127.8 (Ar), 127.7 (Ar), 127.6 (Ar), 127.6
(Ar), 127.6 (Ar), 127.6 (Ar), 127.4 (Ar), 127.3 (Ar),
99.3 (C-10), 97.8 (C-1), 80.4 (C-3), 75.1 (C-2), 75.0
(PhCH2), 74.8 (C-4), 73.6 (C-20), 73.3 (PhCH2), 73.2
(C-30), 73.0 (C-60), 72.7 (PhCH2), 72.5 (PhCH2), 72.2
(PhCH2), 71.6 (C-5), 70.0 (PhCH2), 68.2 (C-50), 67.6
(octyl OCH2), 66.2 (C-6), 31.8 (octyl CH2), 29.4 (octyl
CH2), 29.4 (octyl CH2), 29.2 (octyl CH2), 29.2 (C-40),
26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl CH3).
ESIMS: m/z calcd for [C62H74O10]Na+: 1001.5174.
Found: 1001.5174.
Disaccharide 43 (241 mg, 0.24 mmol) was dissolved in
pyridine (1 mL) and the solution was cooled in an ice
bath followed by the addition of p-toluenesulfonyl chlo-
ride (137 mg, 0.72 mmol). The reaction mixture was stir-
red overnight. The mixture was diluted with CH2Cl2
(25 mL), washed with 1 M HCl (3 · 10 mL), satd aq
NaHCO3 (10 mL), water (10 mL), dried (MgSO4), and
concentrated to a colorless oil. The crude product was
then purified by chromatography (4:1 hexane–EtOAc)
to give 48 (251 mg, 90%) as a colorless oil: Rf 0.37 (4:1
1
hexane–EtOAc); [a]D +27.9 (c 0.9, CHCl3); H NMR
(600 MHz, CDCl3) dH 7.74–7.78 (m, 2H, ArH), 7.14–
7.39 (m, 32H, ArH), 5.04 (d, 1H, J = 1.8 Hz, H-10),
4.88 (d, 1H, J = 10.8 Hz, PhCH2), 4.87 (d, 1H,
J = 10.8 Hz, PhCH2), 4.78 (d, 1H, J = 1.8 Hz, H-1),
4.73 (d, 1H, J = 12.6 Hz, PhCH2), 4.67 (d, 1H,
J = 12.0 Hz, PhCH2), 4.59–4.66 (m, 4H, PhCH2), 4.54
(d, 1H, J = 12.0 Hz, PhCH2), 4.46 (d, 1H, J = 12.0 Hz,
PhCH2), 4.45 (d, 1H, J = 11.4 Hz, PhCH2), 4.42 (d,
1H, J = 10.8 Hz, PhCH2), 4.15–4.21 (m, 2H, H-6a0, H-
6b0), 3.81–3.93 (m, 6H, H-3, H-4, H-6a, H-20, H-30, H-
40), 3.78 (dd, 1H, J = 2.4, 1.8 Hz, H-2), 3.72–3.80 (m,
1H, H-5), 3.61–3.67 (m, 2H, H-50, H-6b), 3.57 (dt, 1H,
J = 9.6, 6.6 Hz, octyl OCH2), 3.31 (dt, 1H, J = 9.6,
6.6 Hz, octyl OCH2), 2.37 (s, 3H, SPhCH3), 1.45–1.53
(m, 2H, octyl OCH2CH2), 1.21–1.34 (m, 10H, octyl
CH2), 0.89 (t, 3H, J = 6.9 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 144.4 (Ar), 138.6 (Ar), 138.5
(Ar), 138.5 (Ar), 138.3 (Ar), 138.1 (Ar), 129.6 (Ar),
3.39. Octyl 2,3,4-tri-O-benzyl-6-O-methyl-a-D-manno-
pyranosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-mannopyran-
oside (47)
Prepared from disaccharide 43 (109 mg, 0.11 mmol) in
DMF (3 mL) and 60% NaH in mineral oil (7.2 mg,
0.18 mmol) and CH3I (12 lL, 0.18 mmol) as described
for 35 to give 47 (107 mg, 96%) as a colorless oil: Rf
0.41 (4:1 hexane–EtOAc); [a]D +31.1 (c 1.2, CHCl3);
1H NMR (500 MHz, CDCl3) dH 7.18–7.40 (m, 30H,
ArH), 5.15 (d, 1H, J = 1.5 Hz, H-10), 4.94 (d, 1H,
J = 11.0 Hz, PhCH2), 4.90 (d, 1H, J = 11.0 Hz, PhCH2),
4.79 (d, 1H, J = 1.5 Hz, H-1), 4.64–4.76 (m, 6H,
PhCH2), 4.59 (d, 1H, J = 11.0 Hz, PhCH2), 4.57 (d,
1H, J = 12.0 Hz, PhCH2), 4.90 (d, 2H, J = 12.0 Hz,

1762
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
128.4 (Ar), 128.3 (Ar), 128.3 (Ar), 128.2 (Ar), 128.0 (Ar),
127.9 (Ar), 127.8 (Ar), 127.8 (Ar), 127.7 (Ar), 127.7 (Ar),
127.7 (Ar), 127.6 (Ar), 127.5 (Ar), 127.5 (Ar), 127.4 (Ar),
98.0 (C-10), 97.8 (C-1), 80.4 (C-3), 79.2 (C-30), 75.1 (C-
2), 75.0 (PhCH2), 74.9 (PhCH2), 74.7 (C-4/C-20/C-40),
74.6 (C-4/C-20/C-40), 73.9 (C-4/C-20/C-40), 72.9
(PhCH2), 72.4 (PhCH2), 72.2 (PhCH2), 71.6 (C-5), 71.3
(PhCH2), 70.0 (C-50), 68.9 (C-60), 67.7 (octyl OCH2),
66.2 (C-6), 59.1 (OCH3), 31.8 (octyl CH2), 29.4 (octyl
CH2), 29.4 (octyl CH2), 29.2 (octyl CH2), 26.2 (octyl
CH2), 22.7 (octyl CH2), 21.6 (SPhCH3), 14.1 (octyl
CH3). Anal. Calcd for C69H80O13S (1149.43): C, 72.10;
H, 7.02; S, 2.79. Found: C, 71.96; H, 6.93; S, 2.66.
ESIMS: m/z calcd for [C69H80O13S]Na+: 1171.5212.
Found: 1171.5211.
CH2), 29.2 (octyl CH2), 26.2 (octyl CH2), 22.7 (octyl
CH2), 18.0 (C-60), 14.1 (octyl CH3). Anal. Calcd for
C62H74O10 (979.24): C, 76.04; H, 7.62. Found: C,
75.97; H, 7.72. ESIMS: m/z calcd for [C62H74O10]Na+:
1001.5174. Found: 1001.5177.
3.42. Octyl 2,3-O-isopropylidene-6-O-(tert-butyldiphen-
ylsilyl)-a-D-mannopyranoside (50)
Triol 30 (595 mg, 1.12 mmol), 2,2-dimethoxypropane
(1.2 mL, 9.0 mmol), and p-TsOH (4.3 mg) were dis-
solved in acetone (15 mL), and the mixture was stirred
for 2 h. The reaction mixture was neutralized with
Et3N, concentrated, and purified by chromatography
(6:1 hexane–EtOAc) to give 50 (615 mg, 96%) as a color-
less oil: Rf 0.29 (6:1 hexane–EtOAc); [a]D +1.0 (c 2.3,
CHCl3); 1H NMR (500 MHz, CDCl3) dH 7.68–7.73
(m, 4H, ArH), 7.36–7.46 (m, 6H, ArH), 4.97 (s, 1H,
H-1), 4.17 (dd, 1H, J = 6.5, 6.5 Hz, H-3), 4.13 (d, 1H,
J = 6.0 Hz, H-2), 3.85–3.94 (m, 2H, H-6a, H-6b), 3.80
(dd, 1H, J = 9.3, 6.5 Hz, H-4), 3.63–3.70 (m, 2H, H-5,
octyl OCH2), 3.38 (dt, 1H, J = 9.5, 6.5 Hz, octyl
OCH2), 2.81 (br s, 1H, OH), 1.51–1.60 (m, 2H, octyl
OCH2CH2), 1.50 (s, 3H, isopropylidene CH3), 1.36 (s,
3H, isopropylidene CH3), 1.20–1.38 (m, 10H, octyl
CH2), 1.07 (s, 9H, tert-butyl CH3), 0.89 (t, 3H,
J = 6.5 Hz, octyl CH3); 13C NMR (125 MHz, CDCl3)
dC 135.8 (4 · Ar), 133.3 (Ar), 133.2 (Ar), 129.9
(2 · Ar), 127.9 (4 · Ar), 109.6 (isopropylidene C), 97.2
(C-1), 78.3 (C-3), 75.6 (C-2), 70.7 (C-4), 69.8 (C-5),
67.9 (octyl OCH2), 64.9 (C-6), 32.0 (octyl CH2), 29.5
(octyl CH2), 29.5 (octyl CH2), 29.4 (octyl CH2), 28.0
(isopropylidene CH3), 27.0 (tert-butyl CH3), 26.3 (tert-
butyl C), 26.2 (isopropylidene CH3), 22.8 (octyl CH2),
19.3 (octyl CH2), 14.2 (octyl CH3). Anal. Calcd for
C33H50O6Si (570.83): C, 69.43; H, 8.83. Found: C,
68.98; H, 8.75. ESIMS: m/z calcd for [C33H50O6Si]Na+:
593.3269. Found: 593.3270.
3.41. Octyl 2,3,4-tri-O-benzyl-6-deoxy-a-D-mannopyr-
anosyl-(1!6)-2,3,4-tri-O-benzyl-a-D-mannopyranoside
(49)
Disaccharide 48 (130 mg, 0.11 mmol) was dissolved in
ether (5 mL), and 1 M LiAlH4 (0.22 mL, 0.22 mmol)
was added. The mixture was stirred overnight and
quenched with EtOAc, followed by water. The mixture
was diluted with EtOAc (25 mL), washed with water
(3 · 10 mL), and dried (MgSO4), filtered, and concen-
trated to a colorless oil. The crude product was purified
by chromatography (9:1 hexane–EtOAc) to give 49
(69 mg, 62%) and 43 (37 mg, 33%) both as colorless oils.
Compound 49: Rf 0.44 (6:1 hexane–EtOAc); [a]D +25.6
1
(c 0.5, CHCl3); H NMR (600 MHz, CDCl3) dH 7.18–
7.40 (m, 30H, ArH), 5.03 (d, 1H, J = 1.8 Hz, H-10),
4.94 (d, 1H, J = 11.8 Hz, PhCH2), 4.90 (d, 1H,
J = 10.8 Hz, PhCH2), 4.79 (d, 1H, J = 1.8 Hz, H-1),
4.73 (d, 1H, J = 11.7 Hz, PhCH2), 4.68 (s, 2H, PhCH2),
4.68 (d, 1H, J = 12.0 Hz, PhCH2), 4.65 (s, 2H, PhCH2),
4.61 (d, 1H, J = 11.7 Hz, PhCH2), 4.57 (d, 1H,
J = 12.0 Hz, PhCH2), 4.51 (d, 1H, J = 11.8 Hz,
PhCH2), 4.51 (d, 1H, J = 10.8 Hz, PhCH2), 3.89–3.97
(m, 4H, H-3, H-4, H-6a, H-20), 3.87 (dd, 1H, J = 9.0,
3.0 Hz, H-30), 3.78 (dd, 1H, J = 2.7, 1.8 Hz, H-2),
3.70–3.76 (m, 1H, H-50), 3.66–3.70 (m, 2H, H-5, H-
6b), 3.55–3.62 (m, 2H, H-40, octyl OCH2), 3.32 (dt,
1H, J = 9.6, 6.6 Hz, octyl OCH2), 1.46–1.53 (m, 2H,
octyl OCH2CH2), 1.21–1.33 (m, 13H, H-60, octyl
CH2), 0.88 (t, 3H, J = 6.9 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 138.8 (Ar), 138.7 (Ar), 138.5
(Ar), 138.5 (Ar), 138.5 (Ar), 138.4 (Ar), 128.5 (Ar),
128.4 (Ar), 128.4 (Ar), 128.3 (Ar), 128.3 (Ar), 128.2
(Ar), 127.9 (Ar), 127.8 (Ar), 127.8 (Ar), 127.7 (Ar),
127.6 (Ar), 127.5 (Ar), 127.4 (Ar), 98.1 (C-10), 97.8 (C-
1), 80.5 (C-3), 80.5 (C-40), 79.5 (C-30), 75.3 (C-20), 75.2
(PhCH2), 75.1 (C-2), 75.1 (PhCH2), 74.7 (C-4), 72.8
(PhCH2), 72.6 (PhCH2), 72.2 (PhCH2), 71.6 (C-5),
71.5 (PhCH2), 68.1 (C-50), 67.6 (octyl OCH2), 66.0 (C-
6), 31.8 (octyl CH2), 29.4 (octyl CH2), 29.4 (octyl
3.43. Octyl 2,3-O-isopropylidene-4-O-benzyl-a-D-manno-
pyranoside (51)
Benzylation of monosaccharide 50 (2.3 g, 4.0 mmol)
using BnBr (0.73 mL, 6.0 mmol) and 60% NaH in min-
eral oil (0.24 g, 6.0 mmol) in DMF (10 mL) was per-
formed as described for 23 to obtain a residue as a
yellow oil. Desilylation of the crude product was per-
formed in THF (50 mL) and TBAF (8.0 mL, 8.0 mmol)
as described for 23 to give 51 (1.29 g, 76% over two
steps) as a crystalline solid. Rf 0.38 (4:1 hexane–EtOAc);
[a]D +45.8 (c 1.2, CHCl3); 1H NMR (400 MHz, CDCl3)
dH 7.26–7.48 (m, 5H, ArH), 5.02 (s, 1H, H-1), 4.77 (d,
1H, J = 11.4 Hz, PhCH2), 4.64 (d, 1H, J = 11.4 Hz,
PhCH2), 4.34 (dd, 1H, J = 6.4, 6.4 Hz, H-3), 4.15 (d,
1H, J = 6.4 Hz, H-2), 3.85 (dd, 1H, J = 11.6, 3.2 Hz,
H-6a), 3.75 (dd, 1H, J = 11.6, 4.8 Hz, H-6b), 3.62–3.72

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1763
(m, 2H, H-5, octyl OCH2), 3.54 (dd, 1H, J = 10.0,
6.4 Hz, H-4), 3.40 (dt, 1H, J = 9.6, 6.4 Hz, octyl
OCH2), 1.94 (br s, 1H, OH), 1.48–1.62 (m, 5H, isopro-
pylidene CH3, octyl OCH2CH2), 1.20–1.49 (m, 13H, iso-
propylidene CH3, octyl CH2), 0.89 (t, 3H, J = 6.8 Hz,
octyl CH3); 13C NMR (100 MHz, CDCl3) dC 138.3
(Ar), 128.5 (2 · Ar), 128.2 (2 · Ar), 127.9 (Ar), 109.4
(isopropylidene C), 97.3 (C-1), 78.9 (C-3), 76.4 (C-2/H-
4), 76.2 (C-2/H-4), 73.0 (PhCH2), 68.5 (C-5), 68.0 (octyl
OCH2), 62.8 (C-6), 31.9 (octyl CH2), 29.5 (octyl CH2),
29.5 (octyl CH2), 29.3 (octyl CH2), 28.1 (isopropylidene
CH3), 26.5 (isopropylidene CH3), 26.3 (octyl CH2), 22.8
(octyl CH2), 14.1 (octyl CH3). Anal. Calcd for C24H38O6
(422.27): C, 68.22; H, 9.06. Found: C, 68.28; H, 9.06.
ESIMS: m/z calcd for [C24H38O6]Na+: 445.2561. Found:
445.2559.
3.45. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-4-O-benzyl-2,3-O-isopropylidene-a-D-manno-
pyranoside (53)
Prepared from thioglycoside 52 (498 mg, 0.71 mmol),
˚
alcohol 51 (250 mg, 0.59 mmol), powdered 4 A mole-
cular sieves (0.5 g), N-iodosuccinimide (210 mg,
0.89 mmol), and TMSOTf (32 lL, 0.18 mmol) as
described for 31 to give 53 (547 mg, 92%) as a yellow
oil: Rf 0.36 (4:1 hexane–EtOAc); [a]D ꢀ1.1 (c 1.5,
CHCl3); 1H NMR (500 MHz, CDCl3) dH 8.10–8.14
(m, 2H, ArH), 8.03–8.07 (m, 2H, ArH), 7.88–7.92 (m,
2H, ArH), 7.81–7.85 (m, 2H, ArH), 7.55–7.61 (m, 2H,
ArH), 7.49–7.54 (m, 1H, ArH), 7.23–7.45 (m, 14H,
ArH), 6.13 (dd, 1H, J = 10.3, 10.3 Hz, H-40), 5.92 (dd,
1H, J = 10.3, 3.3 Hz, H-30), 5.72 (dd, 1H, J = 3.3,
1.5 Hz, H-20), 5.17 (d, 1H, J = 1.5 Hz, H-10), 5.09 (br
s, 1H, H-1), 4.99 (d, 1H, J = 12.0 Hz, PhCH2), 4.66
(dd, 1H, J = 12.3, 2.5 Hz, H-6a0), 4.65 (d, 1H,
J = 12.0 Hz, PhCH2), 4.50 (ddd, 1H, J = 10.3, 2.5 Hz,
H-50), 4.35–4.42 (m, 2H, H-3, H-6b0), 4.21 (d, 1H,
J = 6.0 Hz, H-2), 3.87–3.98 (m, 4H, H-5, H-6a, H-6b,
octyl OCH2), 3.50–3.58 (m, 2H, H-4, octyl OCH2),
1.64–1.72 (m, 2H, octyl OCH2CH2), 1.58 (s, 3H, isopro-
pylidene CH3), 1.41 (s, 3H, isopropylidene CH3), 1.16–
1.42 (m, 10H, octyl CH2), 0.83 (t, 3H, J = 6.8 Hz, octyl
CH3); 13C NMR (125 MHz, CDCl3) dC 166.1 (C@O),
165.4 (C@O), 165.2 (C@O), 165.2 (C@O), 138.1 (Ar),
133.3 (Ar), 133.0 (Ar), 132.9 (Ar), 130.0 (Ar), 129.8
(Ar), 129.8 (Ar), 129.8 (Ar), 129.7 (Ar), 129.4 (Ar),
129.2 (Ar), 129.1 (Ar), 128.5 (Ar), 128.4 (Ar), 128.4
(Ar), 128.4 (Ar), 128.3 (Ar), 127.7 (Ar), 127.7 (Ar),
3.44. p-Tolyl 2,3,4,6-tetra-O-benzoyl-1-thio-a-D-manno-
pyranoside (52)
D-Mannose (2.74 g, 15.0 mmol) was dissolved in pyri-
dine (19 mL) and cooled at 0 ꢁC. Benzoyl chloride
(19.0 mL, 140 mmol) was added dropwise, and the reac-
tion mixture was stirred overnight. The reaction mixture
was then diluted with CH2Cl2 (100 mL), washed
with water (2 · 50 mL), 1 M HCl (3 · 50 mL), satd aq
NaHCO3 (50 mL), dried (MgSO4), and concentrated
to yellow syrup. The crude product (6.29 g, 8.9 mol)
and p-thiocresol (1.3 g, 11.0 mol) were dissolved in
CH2Cl2 (50 mL). After the addition of BF3ÆEt2O
(3.4 mL, 0.061 mol), the reaction mixture was stirred
for 24 h. The solution was diluted with CH2Cl2
(100 mL), washed with satd aq NaHCO3 (50 mL), water
(2 · 50 mL), dried (MgSO4), and concentrated. The
crude product was purified by chromatography (4:1 hex-
ane–EtOAc) to give 52 (3.95 g, 64%) as a white foam: Rf
0.38 (4:1 hexane–EtOAc); [a]D +33.0 (c 2.3, CHCl3); 1H
NMR (400 MHz, CDCl3) dH 8.04–8.10 (m, 4H, ArH),
8.01 (m, 2H, ArH), 7.87 (m, 2H, ArH), 7.59 (m, 3H,
ArH), 7.36–7.48 (m, 9H, ArH), 7.25–7.32 (m, 2H,
ArH), 7.01 (d, 2H, J = 8.0 Hz, ArH), 6.15 (dd, 1H,
J = 10.0, 10.0 Hz, H-4), 5.98 (dd, 1H, J = 3.3, 1.5 Hz,
H-2), 5.90 (dd, 1H, J = 10.0, 3.3 Hz, H-3), 5.72 (d,
1H, J = 1.5 Hz, H-1), 5.03 (ddd, 1H, J = 10.0, 5.0,
2.5 Hz, H-5), 4.67 (dd, 1H, J = 12.5, 2.5 Hz, H-6a),
4.57 (dd, 1H, J = 12.5, 5.0 Hz, H-6b), 2.30 (s, 3H,
SPhCH3); 13C NMR (100 MHz, CDCl3) dC 166.1
(C@O), 165.5 (C@O), 165.4 (C@O), 165.3 (C@O),
138.4 (Ar), 133.5 (2 · Ar), 133.3 (Ar), 133.0 (Ar), 132.7
(2 · Ar), 130.0 (2 · Ar), 129.9 (2 · Ar), 129.9 (2 · Ar),
129.8 (2 · Ar), 129.8 (2 · Ar), 129.5 (Ar), 129.3 (Ar),
128.9 (Ar), 128.9 (Ar), 128.8 (Ar), 128.6 (2 · Ar), 128.5
(2 · Ar), 128.4 (2 · Ar), 128.3 (2 · Ar), 86.3 (C-1), 71.9
(C-2), 70.4 (C-3), 69.8 (C-5), 67.2 (C-4), 63.1 (C-6),
21.1 (SPhCH3). ESIMS: m/z calcd for [C41H34O9S]Na+:
725.1816. Found: 725.1813.
1
109.4 (isopropylidene C), 97.4 (C-10, JC,H = 172.9 Hz),
96.9 (C-1, 1JC,H = 169.9 Hz), 78.8 (C-3), 76.1 (C-2), 76.1
(C-4), 72.6 (PhCH2), 70.4 (C-20), 70.0 (C-30), 68.8 (C-50),
67.8 (octyl OCH2), 67.6 (C-40), 67.1 (C-6), 66.9 (C-5),
62.7 (C-60), 31.8 (octyl CH2), 29.5 (octyl CH2), 29.4
(octyl CH2), 29.3 (octyl CH2), 28.1 (isopropylidene
CH3), 26.4 (isopropylidene CH3), 26.3 (octyl CH2),
22.6 (octyl CH2), 14.0 (octyl CH3). ESIMS: m/z calcd
for [C58H64O15]Na+: 1023.4137. Found: 1023.4133.
3.46. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-4-O-benzyl-a-D-mannopyranoside (54)
Disaccharide 53 (496 mg, 0.50 mmol) was dissolved in
80% AcOH–H2O (10 mL) and heated at 50 ꢁC over-
night. The reaction mixture was then diluted with
EtOAc (50 mL), washed with satd aq NaHCO3
(2 · 25 mL), dried (MgSO4), and concentrated. The
crude residue was purified by chromatography (1:1
hexane–EtOAc) to give 54 (421 mg, 88%) as a colorless
oil: Rf 0.28 (1:1 hexane–EtOAc); [a]D +4.9 (c 1.2,
CHCl3); 1H NMR (600 MHz, CDCl3) dH 8.09–8.12
(m, 2H, ArH), 8.05–8.08 (m, 2H, ArH), 7.93–7.96 (m,
2H, ArH), 7.84–7.88 (m, 2H, ArH), 7.55–7.62 (m,

1764
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
2H, ArH), 7.49–7.54 (m, 1H, ArH), 7.35–7.46 (m, 12H,
ArH), 7.26–7.33 (m, 2H, ArH), 6.14 (dd, 1H, J = 10.2,
10.2 Hz, H-40), 5.93 (dd, 1H, J = 10.2, 3.6 Hz, H-30),
5.75 (dd, 1H, J = 3.6, 1.8 Hz, H-20), 5.38 (d, 1H,
J = 1.8 Hz, H-10), 4.98 (d, 1H, J = 11.4 Hz, PhCH2),
4.85 (d, 1H, J = 1.2 Hz, H-1), 4.82 (d, 1H,
J = 11.4 Hz, PhCH2), 4.69 (dd, 1H, J = 12.2, 2.4 Hz,
H-6a0), 4.51 (ddd, 1H, J = 10.2, 3.9, 2.4 Hz, H-50),
4.44 (dd, 1H, J = 12.2, 3.9 Hz, H-6b0), 4.08 (dd, 1H,
J = 12.0, 4.2 Hz, H-6a), 4.02 (dd, 1H, J = 8.4, 3.6 Hz,
H-3), 3.90–3.96 (m, 2H, H-2, H-6b), 3.77–3.85 (m,
2H, H-4, H-5), 3.72 (dt, 1H, J = 9.6, 6.6 Hz, octyl
OCH2), 3.44 (dt, 1H, J = 9.6, 6.6 Hz, octyl OCH2),
2.65 (br s, 1H, OH), 2.48 (br s, 1H, OH), 1.56–1.63
(m, 2H, octyl OCH2CH2), 1.20–1.40 (m, 10H, octyl
CH2), 0.86 (t, 3H, J = 6.9 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 166.2 (C@O), 165.6 (C@O),
165.5 (C@O), 165.5 (C@O), 138.4 (Ar), 133.5 (Ar),
133.4 (Ar), 133.2 (Ar), 133.0 (Ar), 130.0 (Ar), 129.9
(Ar), 129.7 (Ar), 129.3 (Ar), 129.1 (Ar), 129.1 (Ar),
128.6 (Ar), 128.6 (Ar), 128.4 (Ar), 128.3 (Ar), 128.0
(Ar), 127.9 (Ar), 99.4 (C-1), 97.8 (C-10), 75.9 (C-4),
74.9 (PhCH2), 72.2 (C-3), 71.3 (C-2), 71.0 (C-5), 70.8
(C-20), 69.9 (C-30), 69.0 (C-50), 68.0 (octyl OCH2),
66.9 (C-40), 66.8 (C-6), 62.8 (C-60), 31.8 (octyl CH2),
29.4 (octyl CH2), 29.4 (octyl CH2), 29.2 (octyl CH2),
26.2 (octyl CH2), 22.6 (octyl CH2), 14.1 (octyl CH3).
Anal. Calcd for C50H60O15 (961.06): C, 68.74; H,
6.29. Found: C, 68.23; H, 6.23. ESIMS: m/z calcd for
[C55H60O15]Na+: 983.3824. Found: 983.3823.
4.96 (d, 1H, J = 1.5 Hz, H-1), 4.85 (d, 1H,
J = 11.8 Hz, PhCH2), 4.66 (dd, 1H, J = 12.0, 2.5 Hz,
H-6a0), 4.44 (ddd, 1H, J = 10.0, 3.1, 2.5 Hz, H-50),
4.37–4.40 (m, 2H, H-6b0, H-3), 4.15 (dd, 1H, J = 11.3,
4.3 Hz, H-6a), 3.92–4.02 (m, 3H, H-4, H-5, H-6b),
3.77 (dt, 1H, J = 9.5, 6.8 Hz, octyl OCH2), 3.49 (dt,
1H, J = 9.5, 6.8 Hz, octyl OCH2), 1.59–1.68 (m, 2H,
octyl OCH2CH2), 1.20–1.43 (m, 10H, octyl CH2), 0.87
(t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz,
CDCl3) dC 166.5 (C@O), 166.1 (C@O), 165.4 (C@O),
165.3 (C@O), 165.1 (C@O), 138.2 (Ar), 133.4 (Ar),
133.3 (Ar), 133.3 (Ar), 133.1 (Ar), 133.0 (Ar), 129.9
(Ar), 129.9 (Ar), 129.8 (Ar), 129.7 (Ar), 129.6 (Ar),
129.4 (Ar), 129.2 (Ar), 129.0 (Ar), 128.6 (Ar), 128.6
(Ar), 128.5 (Ar), 128.4 (Ar), 128.4 (Ar), 128.3 (Ar),
128.0 (Ar), 127.8 (Ar), 97.9 (C-10), 97.5 (C-1), 75.9 (C-
4), 75.0 (PhCH2), 73.3 (C-2), 71.1 (C-3), 70.7 (C-5),
70.3 (C-20), 70.2 (C-30), 69.0 (C-50), 68.2 (octyl OCH2),
66.8 (C-40), 66.5 (C-6), 62.7 (C-60), 31.8 (octyl CH2),
29.5 (octyl CH2), 29.4 (octyl CH2), 29.3 (octyl CH2),
26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl CH3).
ESIMS: m/z calcd for [C62H64O16]Na+: 1087.4087.
Found: 1087.4086.
3.47.2. Data for 55. Rf 0.16 (3:1 hexane–EtOAc); [a]D
1
+11.1 (c 1.8, CHCl3); H NMR (500 MHz, CDCl3) dH
8.15–8.19 (m, 2H, ArH), 8.06–8.14 (m, 4H, ArH), 7.95–
7.99 (m, 2H, ArH), 7.86–7.90 (m, 2H, ArH), 7.56–7.62
(m, 3H, ArH), 7.35–7.55 (m, 10H, ArH), 7.19–7.32 (m,
7H, ArH), 6.16 (dd, 1H, J = 10.0, 10.0 Hz, H-40), 5.99
(dd, 1H, J = 10.0, 3.5 Hz, H-30), 5.82 (dd, 1H, J = 3.5,
1.5 Hz, H-20), 5.62 (dd, 1H, J = 9.8, 3.0 Hz, H-3), 5.45
(d, 1H, J = 1.5 Hz, H-10), 4.88 (d, 1H, J = 1.8 Hz, H-
1), 4.85 (d, 1H, J = 11.0 Hz, PhCH2), 4.75 (d, 1H,
J = 11.5 Hz, PhCH2), 4.70 (dd, 1H, J = 11.5, 2.0 Hz,
H-6a0), 4.44–4.52 (m, 2H, H-50, H-6b0), 4.31 (dd, 1H,
J = 9.8, 9.8 Hz, H-4), 4.23 (dd, 1H, J = 3.0, 1.8 Hz, H-
2), 4.10 (dd, 1H, J = 12.0, 4.0 Hz, H-6a), 3.94–4.00 (m,
2H, H-5, H-6b), 3.74 (dt, 1H, J = 9.5, 6.8 Hz, octyl
OCH2), 3.48 (dt, 1H, J = 9.5, 6.8 Hz, octyl OCH2),
1.59–1.67 (m, 2H, octyl OCH2CH2), 1.20–1.42 (m,
10H, octyl CH2), 0.87 (t, 3H, J = 7.0 Hz, octyl CH3);
13C NMR (125 MHz, CDCl3) dC 166.2 (C@O), 165.6
(C@O), 165.6 (C@O), 165.6 (C@O), 165.5 (C@O),
137.8 (Ar), 133.5 (Ar), 133.4 (Ar), 133.2 (Ar), 133.0
(Ar), 130.0 (Ar), 129.9 (Ar), 129.9 (Ar), 129.8 (Ar),
129.4 (Ar), 129.2 (Ar), 129.1 (Ar), 128.6 (Ar), 128.5
(Ar), 128.4 (Ar), 128.4 (Ar), 128.3 (Ar), 128.0 (Ar),
99.7 (C-1), 98.0 (C-10), 75.2 (C-3), 75.0 (PhCH2), 72.9
(C-4), 71.7 (C-5), 70.9 (C-20), 69.9 (C-2/C-30), 69.8 (C-
2/C-30), 69.0 (C-50), 68.3 (octyl OCH2), 67.0 (C-40),
66.5 (C-6), 62.8 (C-60), 31.8 (octyl CH2), 29.4
(octyl CH2), 29.4 (octyl CH2), 29.2 (octyl CH2), 26.2
(octyl CH2), 22.7 (octyl CH2), 14.1 (octyl CH3). ESIMS:
m/z calcd for [C62H64O16]Na+: 1087.4087. Found:
1087.4083.
3.47. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-3-O-benzoyl-4-O-benzyl-a-D-mannopyranoside
(55) and octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyr-
anosyl-(1!6)-2-O-benzoyl-4-O-benzyl-a-D-mannopyr-
anoside (56)
Disaccharide 54 (637 mg, 0.66 mmol) and Bu2SnO
(168 mg, 0.66 mmol) in toluene (15 mL) was heated
under reflux for 3 h. The reaction mixture was cooled
to room temperature, and BzCl (0.10 mL, 0.83 mmol)
was added and stirring was continued overnight. The
solvent was then evaporated and the crude residue was
purified by chromatography (3:1 hexane–EtOAc) to give
55 (442 mg, 63%) and 56 (227 mg, 32%), both as white
foams.
3.47.1. Data for 56. Rf 0.28 (3:1 hexane–EtOAc); [a]D
1
ꢀ2.3 (c 1.9, CHCl3); H NMR (500 MHz, CDCl3) dH
8.08–8.13 (m, 4H, ArH), 7.99–8.04 (m, 2H, ArH), 7.88–
7.92 (m, 2H, ArH), 7.83–7.87 (m, 2H, ArH), 7.53–7.61
(m, 2H, ArH), 7.25–7.53 (m, 18H, ArH), 6.14 (dd, 1H,
J = 10.3, 10.3 Hz, H-40), 5.96 (dd, 1H, J = 10.3,
3.3 Hz, H-30), 5.81 (dd, 1H, J = 3.3, 2.0 Hz, H-20),
5.41 (dd, 1H, J = 3.5, 1.5 Hz, H-2), 5.29 (d, 1H,
J = 2.0 Hz, H-10), 5.05 (d, 1H, J = 11.8 Hz, PhCH2),

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1765
3.48. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-3-O-benzoyl-4-O-benzyl-2-O-phenoxythiocar-
bonyl-a-D-mannopyranoside (57)
1H NMR (500 MHz, CDCl3) dH 8.13–8.17 (m, 2H,
ArH), 8.09–8.13 (m, 2H, ArH), 8.01–8.05 (m, 2H,
ArH), 7.90–7.94 (m, 2H, ArH), 7.84–7.88 (m, 2H,
ArH), 7.55–7.61 (m, 2H, ArH), 7.24–7.54 (m, 21H,
ArH), 7.07–7.11 (m, 2H, ArH), 6.15 (dd, 1H, J = 10.3,
10.3 Hz, H-40), 6.05 (dd, 1H, J = 10.0, 3.5 Hz, H-3),
5.96 (dd, 1H, J = 10.3, 3.0 Hz, H-30), 5.86 (dd, 1H,
J = 3.5, 1.8 Hz, H-2), 5.83 (dd, 1H, J = 3.0, 2.0 Hz, H-
20), 5.30 (d, 1H, J = 2.0 Hz, H-10), 5.02 (d, 1H,
J = 1.8 Hz, H-1), 4.98 (d, 1H, J = 11.8 Hz, PhCH2),
4.79 (d, 1H, J = 11.8 Hz, PhCH2), 4.63–4.68 (m, 1H,
H-6a0), 4.33–4.43 (m, 3H, H-50, H-6b0, H-4), 4.16 (dd,
1H, J = 11.5, 4.0 Hz, H-6a), 4.10 (m, 1H, H-5), 3.95
(dd, 1H, J = 11.5, 1.5 Hz, H-6b), 3.79 (dt, 1H, J = 9.5,
6.5 Hz, octyl OCH2), 3.54 (dt, 1H, J = 9.5, 6.5 Hz, octyl
OCH2), 1.64–1.71 (m, 2H, octyl OCH2CH2), 1.21–1.44
(m, 10H, octyl CH2), 0.86 (t, 3H, J = 7.0 Hz, octyl
CH3); 13C NMR (125 MHz, CDCl3) dC 193.7 (C@S),
166.1 (C@O), 165.7 (C@O), 165.4 (C@O), 165.3
(C@O), 165.1 (C@O), 153.4 (Ar), 137.8 (Ar), 133.4
(Ar), 133.4 (Ar), 133.3 (Ar), 133.2 (Ar), 133.0 (Ar),
129.9 (Ar), 129.9 (Ar), 129.8 (Ar), 129.7 (Ar), 129.5
(Ar), 129.4 (Ar), 129.2 (Ar), 129.0 (Ar), 128.7 (Ar),
128.6 (Ar), 128.5 (Ar), 128.5 (Ar), 128.4 (Ar), 128.3
(Ar), 127.9 (Ar), 127.7 (Ar), 126.5 (Ar), 121.9 (Ar),
98.1 (C-10), 97.7 (C-1), 82.1 (C-3), 75.1 (PhCH2), 73.1
(C-4), 71.0 (C-5), 70.2 (C-20/C-30), 70.1 (C-20/C-30),
69.7 (C-2), 69.0 (C-50), 68.5 (octyl OCH2), 66.8 (C-40),
66.2 (C-6), 62.6 (C-60), 31.8 (octyl CH2), 29.4 (octyl
CH2), 29.4 (octyl CH2), 29.2 (octyl CH2), 26.1 (octyl
CH2), 22.6 (octyl CH2), 14.1 (octyl CH3). Anal. Calcd
for C69H68O17 (1200.42): C, 68.98; H, 5.71; S, 2.67.
Found: C, 69.27; H, 5.71; S, 2.55. ESIMS: m/z calcd
for [C69H68O17]Na+: 1223.4070. Found: 1223.4068.
Disaccharide 55 (224 mg, 0.21 mmol) was dissolved in
CH3CN (2.2 mL), and DMAP (64 mg, 0.52 mmol),
and phenyl chlorothionoformate (37 lL, 0.27 mmol)
were added. The reaction mixture was stirred overnight
and concentrated. The crude product was dissolved in
CH2Cl2 (50 mL), washed with water (15 mL), brine
(15 mL), dried (MgSO4), and concentrated as a yellow
crude. The crude product was purified by chromatogra-
phy (3:1 hexane–EtOAc) to give 57 (186 mg, 74%) as a
foam: Rf 0.40 (3:1 hexane–EtOAc); [a]D +11.2 (c 1.7,
CHCl3); 1H NMR (500 MHz, CDCl3) dH 8.11–8.18
(m, 4H, ArH), 8.03–8.07 (m, 2H, ArH), 7.92–7.96 (m,
2H, ArH), 7.75–7.80 (m, 2H, ArH), 7.55–7.65 (m, 3H,
ArH), 7.48–7.54 (m, 3H, ArH), 7.34–7.45 (m, 7H,
ArH), 7.14–7.31 (m, 10H, ArH), 6.89–6.92 (m, 2H,
ArH), 6.15 (dd, 1H, J = 10.0, 10.0 Hz, H-40), 6.03 (dd,
1H, J = 10.0, 3.5 Hz, H-30), 5.89 (dd, 1H, J = 3.5,
1.5 Hz, H-2), 5.88 (dd, 1H, J = 3.5, 1.5 Hz, H-20), 5.84
(dd, 1H, J = 10.0, 3.5 Hz, H-3), 5.34 (d, 1H,
J = 1.5 Hz, H-10), 5.16 (d, 1H, J = 1.5 Hz, H-1), 4.86
(d, 1H, J = 11.5 Hz, PhCH2), 4.69–4.77 (m, 2H, PhCH2,
H-6a0), 4.46–4.52 (m, 2H, H-50, H-6b0), 4.25 (dd, 1H,
J = 10.0, 10.0 Hz, H-4), 4.05–4.11 (m, 2H, H-5, H-6a),
3.95–4.01 (m, 1H, H-6b), 3.82 (dt, 1H, J = 9.5, 6.5 Hz,
octyl OCH2), 3.57 (dt, 1H, J = 9.5, 6.5 Hz, octyl
OCH2), 1.64–1.72 (m, 2H, octyl OCH2CH2), 1.20–1.46
(m, 10H, octyl CH2), 0.86 (t, 3H, J = 7.0 Hz, octyl
CH3); 13C NMR (125 MHz, CDCl3) dC 194.6 (C@S),
166.2 (C@O), 165.5 (C@O), 165.4 (C@O), 165.3
(C@O), 165.1 (C@O), 153.3 (Ar), 137.7 (Ar), 133.4
(Ar), 133.3 (Ar), 133.3 (Ar), 133.0 (Ar), 133.0 (Ar),
130.0 (Ar), 129.9 (Ar), 129.9 (Ar), 129.8 (Ar), 129.7
(Ar), 129.6 (Ar), 129.5 (Ar), 129.3 (Ar), 129.2 (Ar),
129.1 (Ar), 128.5 (Ar), 128.4 (Ar), 128.4 (Ar), 128.2
(Ar), 128.0 (Ar), 127.9 (Ar), 126.4 (Ar), 121.7 (Ar),
98.2 (C-10), 96.4 (C-1), 79.6 (C-2), 75.2 (PhCH2), 73.5
(C-4), 72.4 (C-3), 71.4 (C-5), 70.6 (C-20), 69.8 (C-30),
69.0 (C-50), 68.6 (octyl OCH2), 67.1 (C-40), 66.6 (C-6),
62.8 (C-60), 31.8 (octyl CH2), 29.4 (octyl CH2), 29.4 (oc-
tyl CH2), 29.3 (octyl CH2), 26.2 (octyl CH2), 22.7 (octyl
CH2), 14.1 (octyl CH3). ESIMS: m/z calcd for
[C69H68O17]Na+: 1223.4070. Found: 1223.4070.
3.50. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-3-O-benzoyl-4-O-benzyl-2-deoxy-a-D-arabino-
hexopyranoside (59)
Prepared from phenoxythiocarbonyl derivative 57
(154 mg, 0.13 mmol) in toluene (2.2 mL), tri-n-butyl-
stannane (55 lL, 0.20 mmol), and AIBN (8 mg,
0.049 mmol) in toluene (9 mL) as described for 40 to
give 59 (113 mg, 84%) as a foam: Rf 0.30 (4:1 hexane–
1
EtOAc); [a]D 13.9 (c 1.7, CHCl3); H NMR (500 MHz,
CD2Cl2) dH 8.08–8.12 (m, 4H, ArH), 8.05–8.09 (m,
2H, ArH), 7.93–7.96 (m, 2H, ArH), 7.84–7.87 (m, 2H,
ArH), 7.58–7.65 (m, 3H, ArH), 7.36–7.56 (m, 10H,
ArH), 7.19–7.33 (m, 7H, ArH), 6.09 (dd, 1H, J = 10.5,
10.5 Hz, H-40), 5.92 (dd, 1H, J = 10.5, 3.5 Hz, H-30),
5.82 (dd, 1H, J = 3.5, 2.0 Hz, H-20), 5.58 (ddd, 1H,
J = 11.5, 9.5, 5.5 Hz, H-3), 5.28 (d, 1H, J = 2.0 Hz, H-
10), 4.97 (br d, 1H, J = 3.5 Hz, H-1), 4.86 (d, 1H,
J = 11.5 Hz, PhCH2), 4.76 (d, 1H, J = 11.5 Hz, PhCH2),
4.66 (dd, 1H, J = 12.0, 2.5 Hz, H-6a0), 4.52 (ddd, 1H,
J = 10.5, 4.3, 2.5 Hz, H-50), 4.43 (dd, 1H, J = 12.0,
3.49. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-2-O-benzoyl-4-O-benzyl-3-O-phenoxythiocar-
bonyl-a-D-mannopyranoside (58)
Prepared from disaccharide 56 (227 mg, 0.21 mmol),
DMAP (64 mg, 0.52 mmol) and phenyl chlorothiono-
formate (37 lL, 0.27 mmol) in CH3CN (1.6 mL) as de-
scribed for 57, to give 58 (180 mg, 70%) as a foam: Rf
0.39 (3:1 hexane–EtOAc); [a]D ꢀ14.1 (c 1.0, CHCl3);

1766
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
4.3 Hz, H-6b0), 4.11 (dd, 1H, J = 11.2, 4.5 Hz, H-6a),
4.00 (ddd, 1H, J = 9.5, 4.5, 1.8 Hz, H-5), 3.96 (dd, 1H,
J = 11.2, 1.8 Hz, H-6b), 3.84 (dd, 1H, J = 9.5, 9.5 Hz,
H-4), 3.75 (ddd, 1H, J = 9.5, 6.5, 6.5 Hz, octyl OCH2),
3.45 (ddd, 1H, J = 9.5, 6.5, 6.5 Hz, octyl OCH2), 2.36
(dd, 1H, J = 13.0, 6.0, 1.0 Hz, H-2eq), 1.87 (ddd, 1H,
J = 13.0, 11.5, 3.5 Hz, H2ax), 1.62–1.72 (m, 2H, octyl
OCH2CH2), 1.20–1.46 (m, 10H, octyl CH2), 0.86 (t,
3H, J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz,
CD2Cl2) dC 166.3 (C@O), 166.0 (C@O), 165.7 (C@O),
165.7 (C@O), 165.7 (C@O), 138.6 (Ar), 133.8 (Ar),
133.8 (Ar), 133.6 (Ar), 133.5 (Ar), 133.4 (Ar), 130.8
(Ar), 130.5 (Ar), 130.1 (Ar), 130.0 (Ar), 130.0 (Ar),
130.0 (Ar), 130.0 (Ar), 129.9 (Ar), 129.7 (Ar), 129.7
(Ar), 129.0 (Ar), 128.9 (Ar), 128.8 (Ar), 128.8 (Ar),
128.7 (Ar), 128.1 (Ar), 128.1 (Ar), 98.3 (C-10), 97.3 (C-
1), 77.3 (C-4), 75.1 (PhCH2), 73.2 (C-3), 71.0 (C-5),
70.8 (C-20/C-30), 70.7 (C-20/C-30), 69.4 (C-50), 68.2 (octyl
OCH2), 67.3 (C-40), 67.1 (C-6), 63.2 (C-60), 35.8 (C-2),
32.3 (octyl CH2), 30.0 (octyl CH2), 29.9 (octyl CH2),
29.7 (octyl CH2), 26.7 (octyl CH2), 23.1 (octyl CH2),
14.2 (octyl CH3). Anal. Calcd for C62H64O15 (1048.42):
C, 70.98; H, 6.15. Found: C, 70.56; H, 6.27. ESIMS:
m/z calcd for [C62H64O15]Na+: 1071.4137. Found:
1071.4138.
(C@O), 137.9 (Ar), 133.4 (Ar), 133.3 (Ar), 133.1 (Ar),
133.1 (Ar), 133.0 (Ar), 130.0 (Ar), 129.9 (Ar), 129.8
(Ar), 129.8 (Ar), 129.7 (Ar), 129.7 (Ar), 129.4 (Ar),
129.2 (Ar), 129.1 (Ar), 128.6 (Ar), 128.6 (Ar), 128.5
(Ar), 128.5 (Ar), 128.4 (Ar), 128.4 (Ar), 128.3 (Ar),
127.8 (Ar), 127.6 (Ar), 127.6 (Ar), 127.0 (Ar), 97.7 (C-
10), 96.4 (C-1), 71.2 (C-4), 70.9 (PhCH2), 70.6 (C-2),
70.4 (C-20), 70.2 (C-30), 69.4 (C-5), 68.8 (C-50), 67.9
(octyl OCH2), 66.9 (C-40), 66.7 (C-6), 62.7 (C-60),
31.8 (octyl CH2), 29.6 (octyl CH2), 29.5 (octyl CH2),
29.3 (octyl CH2), 26.3 (octyl CH2), 22.7 (octyl CH2),
22.7 (C-3), 14.1 (octyl CH3). ESIMS: m/z calcd for
[C62H64O15]Na+: 1071.4137. Found: 1071.4140.
3.52. Octyl 3,4-di-O-benzyl-2-O-methyl-a-D-mannopyr-
anoside (61) and octyl 3,6-di-O-benzyl-2-O-methyl-a-D-
mannopyranoside (68)
Prepared from a solution of AlCl3 (150 mg, 1.1 mmol)
and LiAlH4 (1.1 mmol) in ether (4.1 mL) and 66
(317 mg, 0.63 mmol) in 1:1 CH2Cl2–ether (8 mL) as
described for 27 (except that the reaction mixture was
stirred overnight) to give 61 (194 mg, 66%) and its
regioisomer 68 (19 mg, 6%) as colorless oils.
3.52.1. Data for 61. Rf 0.27 (2:1 hexane–EtOAc); [a]D
1
3.51. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-2-O-benzoyl-4-O-benzyl-3-deoxy-a-D-arabino-
hexopyranoside (60)
+41.9 (c 2.8, CHCl3); H NMR (500 MHz, CDCl3) dH
7.26–7.42 (m, 10H, ArH), 4.93 (d, 1H, J = 10.8 Hz,
PhCH2), 4.85 (d, 1H, J = 1.9 Hz, H-1), 4.74 (s, 2H,
PhCH2), 4.64 (d, 1H, J = 10.8 Hz, PhCH2), 3.93 (dd,
1H, J = 9.8, 3.2 Hz, H-3), 3.86 (dd, 1H, J = 9.8,
9.8 Hz, H4), 3.83 (dd, 1H, J = 11.5, 3.0 Hz, H-6a),
3.77 (dd, 1H, J = 11.5, 5.0 Hz, H-6b), 3.61–3.68 (m,
2H, H-5, octyl OCH2), 3.54 (dd, 1H, J = 3.2, 1.9 Hz,
H-2), 3.52 (s, 3H, OCH3), 3.37 (dt, 1H, J = 9.5,
6.5 Hz, octyl OCH2), 1.97 (br s, 1H, OH), 1.52–1.69
(m, 2H, octyl OCH2CH2), 1.24–1.36 (m, 10H, octyl
CH2), 0.90 (t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 138.4 (Ar), 138.4 (Ar), 128.4
(2 · Ar), 128.4 (2 · Ar), 128.1 (2 · Ar), 127.8 (2 · Ar),
127.7 (Ar), 127.6 (Ar), 97.5 (C-1), 80.1 (C-3), 78.1 (C-
2), 75.3 (PhCH2), 75.0 (C-4), 72.4 (PhCH2), 72.0 (C-5),
67.8 (octyl OCH2), 62.5 (C-6), 59.4 (OCH3), 31.8 (octyl
CH2), 29.5 (octyl CH2), 29.4 (octyl CH2), 29.2 (octyl
CH2), 26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl
CH3). Anal. Calcd for C29H42O6 (486.64): C, 71.57; H,
8.70. Found: C, 71.44; H, 8.78. ESIMS: m/z calcd for
[C29H42O6]Na+: 509.2874. Found: 509.2877.
Prepared from phenoxythiocarbonyl derivative 58
(154 mg, 0.13 mmol) in toluene (2.2 mL) and tri-n-
butylstannane (55 lL, 0.20 mmol) and AIBN (8 mg,
0.049 mmol) in toluene (9 mL) at reflux as described
for 40 to give 60 (42 mg, 32%) as a colorless oil: Rf
1
0.32 (4:1 hexane–EtOAc); [a]D +5.6 (c 0.8, CHCl3); H
NMR (600 MHz, CDCl3) dH 8.08–8.14 (m, 4H, ArH),
8.03–8.06 (m, 2H, ArH), 7.87–7.91 (m, 2H, ArH),
7.83–7.86 (m, 2H, ArH), 7.54–7.61 (m, 2H, ArH),
7.23–7.52 (m, 18H, ArH), 6.14 (dd, 1H, J = 10.2,
10.2 Hz, H-40), 5.98 (dd, 1H, J = 10.2, 3.6 Hz, H-30),
5.81 (dd, 1H, J = 3.6, 1.5 Hz, H-20), 5.27 (d, 1H,
J = 1.5 Hz, H-10), 5.24–5.27 (m, 1H, H-2), 4.87 (br s,
1H, H-1), 4.76 (d, 1H, J = 11.4 Hz, PhCH2), 4.65 (dd,
1H, J = 12.0, 2.4 Hz, H-6a0), 4.58 (d, 1H, J = 11.4 Hz,
PhCH2), 4.49 (ddd, 1H, J = 10.2, 4.2, 2.4 Hz, H-50),
4.36 (dd, 1H, J = 12.0, 4.2 Hz, H-6b0), 4.15 (dd, 1H,
J = 10.9, 4.5 Hz, H-6a), 3.99–4.06 (m, 2H, H-4, H-5),
3.93 (dd, 1H, J = 10.9, 1.2 Hz, H-6b), 3.84 (dt, 1H,
J = 9.6, 6.6 Hz, octyl OCH2), 3.54 (dt, 1H, J = 9.6,
6.6 Hz, octyl OCH2), 2.48 (ddd, 1H, J = 13.4, 3.6,
3.6 Hz, H-3eq), 2.13 (ddd, 1H, J = 13.4, 13.4, 3.0 Hz,
H3ax), 1.58–1.72 (m, 2H, octyl OCH2CH2), 1.20–1.46
(m, 10H, octyl CH2), 0.87 (t, 3H, J = 6.9 Hz, octyl
CH3); 13C NMR (125 MHz, CDCl3) dC 166.1 (C@O),
165.8 (C@O), 165.4 (C@O), 165.3 (C@O), 165.1
3.52.2. Data for 68. Rf 0.44 (2:1 hexane–EtOAc); [a]D
1
+22.6 (c 1.3, CHCl3); H NMR (500 MHz, CDCl3) dH
7.24–7.42 (m, 10H, ArH), 4.89 (d, 1H, J = 2.0 Hz, H-
1), 4.74 (d, 1H, J = 11.8 Hz, PhCH2), 4.65 (d, 1H,
J = 11.8 Hz, PhCH2), 4.57–4.62 (m, 2H, PhCH2), 3.94
(dd, 1H, J = 9.5, 9.5 Hz, H4), 3.67–3.80 (m, 5H, H-3,
H-5, H-6a, H-6b, octyl OCH2), 3.53 (dd, 1H, J = 3.0,

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1767
2.0 Hz, H-2), 3.47 (s, 3H, OCH3), 3.40 (dt, 1H, J = 9.5,
6.5 Hz, octyl OCH2), 2.49 (br s, 1H, OH), 1.53–1.62 (m,
2H, octyl OCH2CH2), 1.22–1.40 (m, 10H, octyl CH2),
0.90 (t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 138.3 (2 · Ar), 128.5 (2 · Ar),
128.3 (2 · Ar), 127.9 (2 · Ar), 127.6 (2 · Ar), 127.5
(2 · Ar), 97.5 (C-1), 79.7 (C-3), 77.3 (C-2), 73.5
(PhCH2), 72.0 (PhCH2), 71.3 (C-5), 70.5 (C-6), 68.0
(C-4), 67.8 (octyl OCH2), 59.1 (OCH3), 31.8 (octyl
CH2), 29.5 (octyl CH2), 29.4 (octyl CH2), 29.3
(octyl CH2), 26.2 (octyl CH2), 22.7 (octyl CH2), 14.1
(octyl CH3). ESIMS: m/z calcd for [C29H42O6]Na+:
509.2874. Found: 509.2876.
9.4 Hz, H-4), 3.73–3.83 (m, 4H, H-2, H-5, H-6a, H-6b),
3.68 (dt, 1H, J = 9.5, 7.0 Hz, octyl OCH2), 3.66 (dd, 1H,
J = 9.4, 3.0 Hz, H-3), 3.36–3.43 (m, 4H, octyl OCH2,
OCH3), 2.57 (br s, 1H, OH), 1.51–1.60 (m, 2H, octyl
OCH2CH2), 1.22–1.36 (m, 10H, octyl CH2), 0.89 (t,
3H, J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz,
CDCl3) dC 138.3 (Ar), 138.2 (Ar), 128.3 (2 · Ar), 128.3
(2 · Ar), 127.8 (2 · Ar), 127.7 (2 · Ar), 127.5 (Ar),
127.5 (Ar), 97.9 (C-1), 81.2 (C-3), 73.5 (PhCH2), 73.0
(C-2), 72.6 (PhCH2), 71.3 (C-5), 70.5 (C-6), 68.0 (C-4),
67.8 (octyl OCH2), 57.2 (OCH3), 31.8 (octyl CH2),
29.4 (octyl CH2), 29.4 (octyl CH2), 29.2 (octyl CH2),
26.2 (octyl CH2), 22.7 (octyl CH2), 14.1 (octyl CH3).
ESIMS: m/z calcd for [C29H42O6]Na+: 509.2874. Found:
509.2877.
3.53. Octyl 2,4-di-O-benzyl-3-O-methyl-a-D-mannopyr-
anoside (62) and octyl 2,6-di-O-benzyl-3-O-methyl-a-D-
mannopyranoside (69)
3.54. Octyl 2,3:4,6-di-O-benzylidene-a-D-mannopyran-
oside (63)
Prepared from a solution of AlCl3 (150 mg, 1.1 mmol)
and LiAlH4 (1.1 mmol) in ether (4.1 mL) and disaccha-
ride 67 (317 mg, 0.66 mmol) in 1:1 CH2Cl2–ether (8 mL)
as described for 27 (except that the reaction mixture was
stirred overnight) to give 62 (182 mg, 57%) and 69
(71 mg, 22%) as colorless oils.
Prepared from tetraol 2927 (3.68 g, 12.6 mmol), benz-
aldehyde dimethyl acetal (2.5 mL, 16.4 mmol), and
p-TsOH (24 mg, 0.13 mmol) in DMF (5.0 mL) as de-
scribed for 25 and 26 to give an ꢁ1:1 mixture of diaste-
reomers 63 (5.10 g, 86%) as a colorless oil: Rf 0.35 (12:1
1
hexane–EtOAc); H NMR (500 MHz, CDCl3) dH 7.23–
3.53.1. Data for 62. Rf 0.33 (3:1 hexane–EtOAc); [a]D
+42.8 (c 3.0, CHCl3); H NMR (500 MHz, CDCl3) dH
7.67 (m, 20H, Ar), 6.30 (s, 1H), 5.98 (s, 1H), 5.66 (s, 1H),
5.54 (s, 1H), 5.12 (s, 1H), 5.19 (s, 1H), 4.67 (t, 1H,
6.5 Hz), 4.51 (t, 1H, 6.5 Hz), 4.24–4.38 (m, 4H), 4.16
(d, 1H, J = 6.6 Hz), 3.68–3.80 (m, 9H), 3.41–4.52 (m,
2H), 1.54–1.67 (m, 4H, octyl OCH2CH2), 1.23–1.46
(m, 20H, octyl CH2), 0.86–0.96 (m, 6H, octyl CH3);
13C NMR (100 MHz, CDCl3) dC 138.7, 137.3, 137.2,
137.1, 129.7, 129.4, 129.1, 129.0, 129.0, 128.5, 128.4,
128.3, 128.2, 128.2, 126.6, 126.3, 126.3, 126.1, 104.1,
103.0, 102.0, 101.7, 97.8, 97.6, 80.7, 78.6, 77.7, 77.3,
77.0, 76.8, 75.6, 75.5, 74.2, 69.0, 68.9, 68.2, 68.1, 60.4,
60.4, 31.8, 31.8, 29.4, 29.4, 29.4, 29.2, 29.2, 26.2, 26.1,
22.7, 22.7, 14.1.
1
7.26–7.42 (m, 10H, ArH), 4.93 (d, 1H, J = 11.5 Hz,
PhCH2), 4.81 (d, 1H, J = 12.0 Hz, PhCH2), 4.80 (d,
1H, J = 1.8 Hz, H-1), 4.71 (d, 1H, J = 12.0 Hz, PhCH2),
4.65 (d, 1H, J = 11.5 Hz, PhCH2), 3.88 (dd, 1H,
J = 10.0, 10.0 Hz, H-4), 3.84 (dd, 1H, J = 11.5, 3.0 Hz,
H-6a), 3.81 (dd, 1H, J = 3.3, 1.8 Hz, H-2), 3.77 (dd,
1H, J = 11.5, 5.0 Hz, H-6b), 3.59–3.67 (m, 3H, H-3,
H-5, octyl OCH2), 3.47 (s, 3H, OCH3), 3.34 (dt, 1H,
J = 9.5, 6.5 Hz, octyl OCH2), 2.00 (br s, 1H, OH),
1.48–1.56 (m, 2H, octyl OCH2CH2), 1.22–1.34 (m,
10H, octyl CH2), 0.89 (t, 3H, J = 7.0 Hz, octyl CH3);
13C NMR (125 MHz, CDCl3) dC 138.6 (Ar), 138.4
(Ar), 128.4 (2 · Ar), 128.4 (2 · Ar), 128.0 (2 · Ar),
127.8 (2 · Ar), 127.7 (Ar), 127.7 (Ar), 98.1 (C-1), 82.1
(C-3), 75.1 (PhCH2), 75.1 (C-4), 74.4 (C-2), 72.9
(PhCH2), 71.9 (C-5), 67.8 (octyl OCH2), 62.5 (C-6),
57.7 (OCH3), 31.8 (octyl CH2), 29.4 (octyl CH2), 29.4
(octyl CH2), 29.2 (octyl CH2), 26.1 (octyl CH2), 22.6
(octyl CH2), 14.1 (octyl CH3). Anal. Calcd for
C29H42O6 (486.64): C, 71.57; H, 8.70. Found: C, 71.40;
H, 8.78. ESIMS: m/z calcd for [C29H42O6]Na+:
509.2874. Found: 509.2875.
3.55. Octyl 3-O-benzyl-4,6-O-benzylidene-a-D-manno-
pyranoside (64) and octyl 2-O-benzyl-4,6-O-benzylidene-
a-D-mannopyranoside (65)
Prepared from a solution of AlCl3 (1.63 g, 12.2 mmol)
and LiAlH4 (12.2 mmol) in ether (47.2 mL) and 63
(4.77 g, 10.2 mmol) in 1:1 CH2Cl2–ether (70 mL) at
0 ꢁC as described for 27 to give 65 (1.72 g, 36%) and
64 (1.52 g, 32%) as a colorless oil.
3.55.1. Data for 65. Rf 0.40 (4:1 hexane–EtOAc); [a]D
1
3.53.2. Data for 69. Rf 0.26 (3:1 hexane–EtOAc); [a]D
+3.7 (c 2.1, CHCl3); H NMR (500 MHz, CDCl3) dH
7.24–7.40 (m, 10H, ArH), 4.89 (d, 1H, J = 1.5 Hz,
H-1), 4.71 (d, 1H, J = 12.5 Hz, PhCH2), 4.68 (d, 1H,
J = 12.5 Hz, PhCH2), 4.64 (d, 1H, J = 12.5 Hz, PhCH2),
4.60 (d, 1H, J = 12.5 Hz, PhCH2), 3.98 (dd, 1H, J = 9.4,
+14.2 (c 4.0, CHCl3); H NMR (400 MHz, CDCl3) dH
1
7.49–7.52 (m, 2H, ArH), 7.26–7.41 (m, 8H, ArH), 5.59
(s, 1H, benzylidene H), 4.84 (d, 1H, J = 1.2 Hz, H-1),
4.77 (d, 1H, J = 11.8 Hz, PhCH2), 4.72 (d, 1H,
J = 11.8 Hz, PhCH2), 4.26 (dd, 1H, J = 9.0, 3.8 Hz H-
6a), 4.11 (dd, 1H, J = 9.4, 3.6 Hz, H-3), 3.92 (dd, 1H,

1768
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
J = 9.4, 9.4 Hz, H-4), 3.76–3.87 (m, 3H, H-2, H-5, H-
6b), 3.67 (dt, 1H, J = 9.6, 6.8 Hz, octyl OCH2), 3.38
(dt, 1H, J = 9.6, 6.8 Hz, octyl OCH2), 2.30 (br s, 1H,
OH), 1.54–1.59 (m, 2H, octyl OCH2CH2), 1.24–1.40
(m, 10H, octyl CH2), 0.91 (t, 3H, J = 6.8 Hz, octyl
CH3); 13C NMR (100 MHz, CDCl3) dC 137.7 (Ar),
137.4 (Ar), 129.0 (Ar), 128.6 (Ar), 128.2 (2 · Ar), 128.0
(2 · Ar), 127.9 (2 · Ar), 126.3 (2 · Ar), 102.1 (benzyli-
dene CH), 98.3 (C-1), 79.6 (C-4), 78.7 (C-2), 73.7
(PhCH2), 68.9 (C-6), 68.8 (C-3), 68.0 (octyl OCH2),
63.4 (C-5), 31.8 (octyl CH2), 29.4 (octyl CH2), 29.3
(octyl CH2), 29.2 (octyl CH2), 26.1 (octyl CH2), 22.7
(octyl CH2), 14.1 (octyl CH3). Anal. Calcd for
C28H38O6 (470.60): C, 71.46; H, 8.14. Found: C, 71.75;
H, 8.34. ESIMS: m/z calcd for [C28H38O6]H+:
471.2741. Found: 471.2742.
1H, J = 9.8, 9.6, 4.2 Hz, H-5), 3.68 (dt, 1H, J = 9.6,
7.0 Hz, octyl OCH2), 3.61 (dd, 1H, J = 3.3, 1.6 Hz, H-
2), 3.58 (s, 3H, OCH3), 3.41 (dt, 1H, J = 9.6, 7.0 Hz,
octyl OCH2), 1.54–1.62 (m, 2H, octyl OCH2CH2), 1.24–
1.39 (m, 10H, octyl CH2), 0.91 (t, 3H, J = 7.0 Hz, octyl
CH3); 13C NMR (100 MHz, CDCl3) dC 138.7 (Ar), 137.7
(Ar), 129.2 (Ar), 128.8 (Ar), 128.3 (2 · Ar), 128.2
(2 · Ar), 127.5 (2 · Ar), 126.0 (2 · Ar), 101.4 (benzyl-
idene CH), 98.9 (C-1), 79.8 (C-2), 79.3 (C-4), 76.4 (C-
3), 73.2 (PhCH2), 68.9 (C-6), 67.9 (octyl OCH2), 64.1
(C-5), 60.1 (OCH3), 31.8 (octyl CH2), 29.4 (octyl
CH2), 29.4 (octyl CH2), 29.2 (octyl CH2), 26.1 (octyl
CH2), 22.7 (octyl CH2), 14.1 (octyl CH3). Anal. Calcd
for C29H40O6 (484.62): C, 71.87; H, 8.32. Found: C,
71.57; H, 8.37. ESIMS: m/z calcd for [C29H40O6]Na+:
507.2717. Found: 507.2716.
3.55.2. Data for 64. Rf 0.23 (4:1 hexane–EtOAc); [a]D
+40.8 (c 2.4, CHCl3); H NMR (400 MHz, CDCl3) dH
3.57. Octyl 2-O-benzyl-4,6-O-benzylidene-3-O-methyl-a-
D-mannopyranoside (67)
1
7.51–7.53 (m, 2H, ArH), 7.26–7.42 (m, 8H, ArH), 5.63
(s, 1H, benzylidene H), 4.88 (d, 1H, J = 11.6 Hz,
PhCH2), 4.87 (d, 1H, J = 1.4 Hz, H-1), 4.74 (d, 1H,
J = 11.6 Hz, PhCH2), 4.24–4.33 (m, 1H, H-6a), 4.11
(dd, 1H, J = 9.4, 9.4 Hz, H-4), 4.07 (dd, 1H, J = 3.5,
1.4 Hz, H-2), 3.94 (dd, 1H, J = 9.4, 3.5 Hz, H-3), 3.81–
3.91 (m, 2H, H-5, H-6b), 3.69 (dt, 1H, J = 9.6, 6.8 Hz,
octyl OCH2), 3.42 (dt, 1H, J = 9.6, 6.8 Hz, octyl
OCH2), 2.68 (br s, 1H, OH), 1.54–1.62 (m, 2H, octyl
OCH2CH2), 1.23–1.40 (m, 10H, octyl CH2), 0.90 (t,
3H, J = 6.8 Hz, octyl CH3); 13C NMR (100 MHz,
CDCl3) dC 138.1 (Ar), 137.6 (Ar), 129.4 (Ar), 128.4
(Ar), 128.9 (2 · Ar), 128.2 (2 · Ar), 127.8 (2 · Ar),
126.0 (2 · Ar), 101.5 (benzylidene CH), 99.9 (C-1),
79.0 (C-4), 75.8 (C-3), 73.1 (PhCH2), 70.1 (C-2), 68.9
(C-6), 68.0 (octyl OCH2), 63.2 (C-5), 31.8 (octyl CH2),
29.4 (octyl CH2), 29.4 (octyl CH2), 29.2 (octyl CH2),
26.1 (octyl CH2), 22.6 (octyl CH2), 14.1 (octyl CH3).
Anal. Calcd for C28H38O6 (470.60): C, 71.46; H, 8.14.
Found: C, 71.33; H, 8.55. ESIMS: m/z calcd for
[C28H38O6]Na+: 493.2561. Found: 493.2561.
Prepared from monosaccharide 65 (461 mg, 0.98 mmol),
60% NaH in mineral oil (60 mg, 1.5 mmol), and CH3I
(0.20 mL, 3.0 mmol) in DMF (15 mL) as described for
35 to give 67 (444 mg, 92%) as a colorless oil: Rf 0.41
(6:1 hexane–EtOAc); [a]D +39.9 (c 1.3, CHCl3); 1H
NMR (400 MHz, CDCl3) dH 7.49–7.55 (m, 2H, ArH),
7.27–7.44 (m, 8H, ArH), 5.63 (s, 1H, benzylidene),
4.84 (d, 1H, J = 12.0 Hz, PhCH2), 4.80 (d, 1H,
J = 1.6 Hz, H-1), 4.72 (d, 1H, J = 12.0 Hz, PhCH2),
4.26 (dd, 1H, J = 9.8, 4.2 Hz, H-6a), 4.18 (dd, 1H,
J = 9.8, 9.8 Hz, H-4), 3.88 (dd, 1H, J = 9.8, 9.8 Hz, H-
6b), 3.87 (dd, 1H, J = 3.2, 1.6 Hz, H-2), 3.82 (ddd,
1H, J = 9.8, 9.8, 4.2 Hz, H-5), 3.75 (dd, 1H, J = 9.8,
3.2 Hz, H-3), 3.66 (dt, 1H, J = 9.6, 6.8 Hz, octyl
OCH2), 3.52 (s, 3H, OCH3), 3.37 (dt, 1H, J = 9.6,
6.8 Hz, octyl OCH2), 1.52–1.62 (m, 2H, octyl
OCH2CH2), 1.24–1.38 (m, 10H, octyl CH2), 0.91 (t,
3H, J = 7.2 Hz, octyl CH3); 13C NMR (100 MHz,
CDCl3) dC 138.2 (Ar), 137.7 (Ar), 128.8 (Ar), 128.4
(2 · Ar), 128.2 (2 · Ar), 128.0 (2 · Ar), 127.7 (Ar),
126.1 (2 · Ar), 101.6 (benzylidene CH), 99.2 (C-1),
79.1 (C-4), 78.1 (C-3), 75.9 (C-2), 73.5 (PhCH2), 68.9
(C-6), 67.9 (octyl OCH2), 64.1 (C-5), 58.8 (OCH3),
31.8 (octyl CH2), 29.4 (octyl CH2), 29.4 (octyl CH2),
29.2 (octyl CH2), 26.1 (octyl CH2), 22.7 (octyl CH2),
14.1 (octyl CH3). ESIMS: m/z calcd for [C29H40O6]Na+:
507.2717. Found: 507.2715.
3.56. Octyl 3-O-benzyl-4,6-O-benzylidene-2-O-methyl-a-
D-mannopyranoside (66)
Prepared from monosaccharide 64 (461 mg, 0.98 mmol),
60% NaH in mineral oil (60 mg, 1.5 mmol), and CH3I
(0.20 mL, 3.0 mmol) in DMF (15 mL) as described for
35 to give 66 (445 mg, 94%) as a colorless oil: Rf 0.48
(4:1 hexane–EtOAc); [a]D +56.15 (c 3.1, CHCl3); 1H
NMR (400 MHz, CDCl3) dH 7.49–7.54 (m, 2H, ArH),
7.26–7.43 (m, 8H, ArH), 5.64 (s, 1H, benzylidene H),
4.91 (d, 1H, J = 12.4 Hz, PhCH2), 4.85 (d, 1H,
J = 1.6 Hz, H-1), 4.74 (d, 1H, J = 12.4 Hz, PhCH2),
4.26 (dd, 1H, J = 9.8, 4.2 Hz, H-6a), 4.17 (dd, 1H,
J = 9.6, 9.6 Hz, H-4), 3.98 (dd, 1H, J = 9.8, 3.3 Hz, H-
3), 3.87 (dd, 1H, J = 9.8, 9.8 Hz, H-6b), 3.80 (ddd,
3.58. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-3,4-di-O-benzyl-2-O-methyl-a-D-mannopyranoside
(70)
Prepared from thioglycoside 52 (252 mg, 0.36 mmol),
˚
alcohol 61 (145 mg, 0.29 mmol), powdered 4 A molecu-
lar sieves (250 mg), N-iodosuccinimide (110 mg,
0.44 mmol), and TMSOTf (27 mg, 0.12 mmol) in

P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
1769
CH2Cl2 (10 mL) as described for 31 to give 70 (272 mg,
89%) as a yellow oil: Rf 0.37 (3:1 hexane–EtOAc); [a]D
+5.6 (c 0.7, CHCl3); H NMR (500 MHz, CDCl3) dH
PhCH2), 4.63 (dd, 1H, J = 12.4, 2.5 Hz, H-6a0), 4.51
(ddd, 1H, J = 10.3, 3.8, 2.5 Hz, H-50), 4.43 (dd, 1H,
J = 12.4, 3.8 Hz, H-6b0), 3.99 (dd, 1H, J = 11.0,
5.5 Hz, H-6a), 3.80–3.92 (m, 4H, H-2, H-4, H-5, H-
6b), 3.76 (dt, 1H, J = 9.5, 7.0 Hz, octyl OCH2), 3.69
(dd, 1H, J = 9.0, 3.0 Hz, H-3), 3.39–3.48 (m, 4H,
OCH3, octyl OCH2), 1.54–1.64 (m, 2H, octyl
OCH2CH2), 1.16–1.42 (m, 10H, octyl CH2), 0.84 (t,
3H, J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz,
CDCl3) dC 166.2 (C@O), 165.4 (C@O), 165.2 (C@O),
165.2 (C@O), 138.6 (Ar), 138.4 (Ar), 133.3 (Ar), 133.0
(Ar), 133.0 (Ar), 130.0 (Ar), 129.9 (Ar), 129.8 (Ar),
129.8 (Ar), 129.7 (Ar), 129.5 (Ar), 129.3 (Ar), 129.2
(Ar), 128.5 (Ar), 128.4 (Ar), 128.4 (Ar), 128.4 (Ar),
128.3 (Ar), 128.2 (Ar), 127.9 (Ar), 127.8 (Ar), 127.6
1
8.11–8.14 (m, 2H, ArH), 8.04–8.08 (m, 2H, ArH),
7.90–7.94 (m, 2H, ArH), 7.81–7.85 (m, 2H, ArH),
7.55–7.61 (m, 2H, ArH), 7.48–7.53 (m, 1H, ArH),
7.23–7.46 (m, 19H, ArH), 6.11 (dd, 1H, J = 10.0,
10.0 Hz, H-40), 5.94 (dd, 1H, J = 10.0, 3.3 Hz, H-30),
5.75 (dd, 1H, J = 3.3, 1.5 Hz, H-20), 5.19 (d, 1H,
J = 1.5 Hz, H-10), 5.03 (d, 1H, J = 11.5 Hz, PhCH2),
4.90 (d, 1H, J = 2.0 Hz, H-1), 4.78 (d, 1H,
J = 11.5 Hz, PhCH2), 4.74 (d, 1H, J = 11.5 Hz, PhCH2),
4.61–4.69 (m, 2H, H-6a0, PhCH2), 4.51 (ddd, 1H,
J = 10.0, 4.3, 4.3 Hz, H-50), 4.44 (dd, 1H, J = 12.3,
4.3 Hz, H-6b0), 3.94–4.00 (m, 2H, H-3, H-6a), 3.83–
3.90 (m, 3H, H-4, H-5, H-6b), 3.80 (dt, 1H, J = 10.0,
6.5 Hz, octyl OCH2), 3.58 (dd, 1H, J = 3.0, 2.0 Hz, H-
2), 3.52 (s, 3H, OCH3), 3.46 (dt, 1H, J = 10.0, 6.5 Hz,
octyl OCH2), 1.58–1.70 (m, 2H, octyl OCH2CH2),
1.19–1.43 (m, 10H, octyl CH2), 0.85 (t, 3H,
J = 7.0 Hz, octyl CH3); 13C NMR (125 MHz, CDCl3)
dC 166.2 (C@O), 165.4 (C@O), 165.2 (C@O), 165.2
(C@O), 138.4 (Ar), 133.3 (Ar), 133.0 (Ar), 129.9 (Ar),
129.8 (Ar), 129.7 (Ar), 129.7 (Ar), 129.5 (Ar), 129.3
(Ar), 129.2 (Ar), 128.5 (Ar), 128.4 (Ar), 128.4 (Ar),
128.2 (Ar), 127.9 (Ar), 127.7 (Ar), 127.7 (Ar), 97.6 (C-
1
(Ar), 127.6 (Ar), 97.7 (C-10, JC,H = 175.8 Hz), 96.9
1
(C-1, JC,H = 175.8 Hz), 82.2 (C-3), 75.0 (PhCH2),
74.9 (C-4), 74.1 (C-2), 72.7 (PhCH2), 71.1 (C-5), 70.5
(C-20), 70.0 (C-30), 68.7 (C-50), 67.8 (octyl OCH2),
67.2 (C-6), 67.1 (C-40), 62.7 (C-60), 57.5 (OCH3), 31.8
(octyl CH2), 29.5 (octyl CH2), 29.5 (octyl CH2), 29.3
(octyl CH2), 26.2 (octyl CH2), 22.6 (octyl CH2), 14.1
(octyl CH3). ESIMS: m/z calcd for [C63H68O15]Na+:
1087.4450. Found: 1087.4451.
3.60. Octyl 2,3-O-isopropylidene-4-O-methyl-a-D-
mannopyranoside (72)
1
1
10, JC,H = 175.8 Hz), 97.1 (C-1, JC,H = 169.9 Hz),
80.4 (C-3), 77.9 (C-2), 75.2 (PhCH2), 74.8 (C-4), 72.3
(PhCH2), 71.3 (C-5), 70.5 (C-20), 70.0 (C-30), 68.7
(C-50), 67.9 (octyl OCH2), 67.1 (C-6), 67.1 (C-40), 62.8
(C-60), 59.2 (OCH3), 31.8 (octyl CH2), 29.6 (octyl
CH2), 29.5 (octyl CH2), 29.3 (octyl CH2), 26.3 (octyl
CH2), 22.7 (octyl CH2), 14.1 (octyl CH3). ESIMS: m/z
calcd for [C63H68O15]Na+: 1087.4450. Found:
1087.4455.
Methylation of monosaccharide 50 (735 mg, 1.3 mmol)
was carried out using CH3I (0.25 mL, 3.9 mmol) and
60% NaH in mineral oil (77 mg, 1.9 mmol) in DMF
(20 mL) as described for 35. The crude product that
was desilylated in THF (8 mL) and TBAF (2.6 mL,
2.6 mmol) as described for 23 to give 72 (395 mg,
89% over two steps) as a colorless oil: Rf 0.23 (4:1 hex-
ane–EtOAc); [a]D +47.4 (c 2.6, CHCl3); 1H NMR
(500 MHz, CDCl3) dH 5.00 (s, 1H, H-1), 4.20 (dd,
1H, J = 7.0, 7.0 Hz, H-3), 4.11 (d, 1H, J = 7.0 Hz, H-
2), 3.91 (dd, 1H, J = 11.5, 3.5 Hz, H-6a), 3.74 (dd,
1H, J = 11.5, 4.5 Hz, H-6b), 3.67 (dt, 1H, J = 9.5,
6.5 Hz, octyl OCH2), 3.52–3.58 (m, 4H, H-5, OCH3),
3.40 (dt, 1H, J = 9.5, 6.5 Hz, octyl OCH2), 3.31 (dd,
1H, J = 10.0, 7.0 Hz, H-4), 2.00 (br s, 1H, OH),
1.50–1.60 (m, 5H, isopropylidene CH3, octyl
OCH2CH2), 1.20–1.38 (m, 13H, isopropylidene CH3,
octyl CH2), 0.88 (t, 3H, J = 7.0 Hz, octyl CH3); 13C
NMR (125 MHz, CDCl3) dC 109.2 (isopropylidene
C), 97.1 (C-1), 78.4 (C-3), 78.4 (C-4), 75.9 (C-2), 68.3
(C-5), 67.8 (octyl OCH2), 62.6 (C-6), 59.2 (OCH3),
31.8 (octyl CH2), 29.4 (octyl CH2), 29.4 (octyl CH2),
29.2 (octyl CH2), 28.0 (isopropylidene CH3), 26.3 (iso-
propylidene CH3), 26.1 (octyl CH2), 22.6 (octyl CH2),
14.1 (octyl CH3). Anal. Calcd for C18H34O6 (346.46):
C, 62.40; H, 9.89. Found: C, 62.45; H, 10.01. ESIMS:
m/z calcd for [C18H34O6]Na+: 369.2248. Found:
369.2248.
3.59. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-2,4-di-O-benzyl-3-O-methyl-a-D-mannopyranoside
(71)
Prepared from thioglycoside 52 (225 mg, 0.32 mmol),
˚
alcohol 62 (130 mg, 0.27 mmol), powdered 4 A molecu-
lar sieves (225 mg), N-iodosuccinimide (96 mg,
0.41 mmol), and TMSOTf (24 mg, 0.11 mmol) in
CH2Cl2 (9 mL) as described for 31 to give 71 (275 mg,
96%) as a yellow oil: Rf 0.26 (4:1 hexane–EtOAc);
1
[a]D +2.1 (c 1.4, CHCl3); H NMR (500 MHz, CDCl3)
dH 8.10–8.14 (m, 2H, ArH), 8.04–8.08 (m, 2H, ArH),
7.90–7.94 (m, 2H, ArH), 7.80–7.84 (m, 2H, ArH),
7.48–7.62 (m, 3H, ArH), 7.20–7.44 (m, 19H, ArH),
6.11 (dd, 1H, J = 10.3, 10.3 Hz, H-40), 5.94 (dd, 1H,
J = 10.3, 3.3 Hz, H-30), 5.75 (dd, 1H, J = 3.3, 2.0 Hz,
H-20), 5.20 (d, 1H, J = 2.0 Hz, H-10), 5.02 (d, 1H,
J = 12.3 Hz, PhCH2), 4.84 (d, 1H, J = 1.5 Hz, H-1),
4.79 (d, 1H, J = 13.0 Hz, PhCH2), 4.73 (d, 1H,
J = 13.0 Hz, PhCH2), 4.67 (d, 1H, J = 12.3 Hz,

1770
P.-H. Tam, T. L. Lowary / Carbohydrate Research 342 (2007) 1741–1772
3.61. Octyl 2,3-O-isopropylidene-4-O-phenoxythiocar-
bonyl-6-O-tert-butyldiphenylsilyl-a-D-mannopyranoside
(73)
(2 · Ar), 129.6 (Ar), 129.6 (Ar), 127.6 (4 · Ar), 108.7
(isopropylidene C), 97.4 (C-1), 73.4 (C-3), 71.0 (C-2),
67.4 (C-6), 67.0 (C-5), 66.7 (octyl OCH2), 31.8 (octyl
CH2), 30.7 (C-4), 29.4 (octyl CH2), 29.4 (octyl CH2),
29.2 (octyl CH2), 28.1 (isopropylidene CH3), 26.8 (tert-
butyl CH3), 26.3 84 (isopropylidene CH3), 26.2 (tert-
butyl, C), 22.6 (octyl CH2), 19.2 (octyl CH2), 14.1 (octyl
CH3). Anal. Calcd for C33H50O5Si (554.34): C, 71.44; H,
9.08. Found: C, 71.45; H, 9.19. ESIMS: m/z calcd for
[C33H50O5Si]Na+: 577.3320. Found: 577.3321.
Prepared from monosaccharide 50 (404 mg, 0.71 mmol),
DMAP (220 mg, 1.78 mmol), and phenyl chlorothiono-
formate (0.13 mL, 0.92 mmol) in CH3CN (2 mL) as de-
scribed for 57, to give 73 (419 mg, 84%) as a colorless
oil: Rf 0.58 (9:1 hexane–EtOAc); [a]D ꢀ21.3 (c 1.4,
CHCl3); 1H NMR (500 MHz, CDCl3) dH 7.69–7.75
(m, 4H, ArH), 7.33–7.46 (m, 8H, ArH), 7.25–7.29 (m,
1H, ArH), 6.88–6.92 (m, 2H, ArH), 5.60 (dd, 1H,
J = 10.3, 7.0 Hz, H-4), 5.11 (br s, 1H, H-1), 4.46 (dd,
1H, J = 7.0, 5.5 Hz, H-3), 4.23 (d, 1H, J = 5.5 Hz, H-
2), 3.94–4.00 (m, 1H, H-5), 3.78–3.89 (m, 3H, H-6a,
H-6b, octyl OCH2), 3.46 (dt, 1H, J = 9.5, 6.8 Hz, octyl
OCH2), 2.09 (br s, 1H, OH), 1.56–1.64 (m, 2H, octyl
OCH2CH2), 1.59 (s, 3H, isopropylidene CH3), 1.39 (s,
3H, isopropylidene CH3), 1.22–1.39 (m, 10H, octyl
CH2), 1.07 (s, 9H, tert-butyl CH3), 0.89 (t, 3H, J =
7.0 Hz, octyl CH3); 13C NMR (125 MHz, CDCl3) dC
194.8 (C@S), 153.5 (Ar), 135.8 (2 · Ar), 135.6 (2 · Ar),
133.3 (Ar), 133.2 (Ar), 129.6 (Ar), 129.6 (Ar), 129.4
(2 · Ar), 127.7 (2 · Ar), 127.7 (2 · Ar), 126.5 (Ar),
121.9 (2 · Ar), 110.1 (isopropylidene C), 96.6 (C-1),
79.9 (C-4), 76.1 (C-2), 75.7 (C-3), 69.2 (C-5), 67.6 (octyl
OCH2), 63.1 (C-6), 31.8 (octyl CH2), 29.5 (octyl CH2),
29.4 (octyl CH2), 29.3 (octyl CH2), 27.6 (isopropylidene
CH3), 26.8 (tert-butyl CH3), 26.5 (isopropylidene CH3),
26.2 (tert-butyl C), 22.7 (octyl CH2), 19.2 (octyl CH2),
14.1 (octyl CH3). Anal. Calcd for C40H54O7SSi
(706.34): C, 67.95; H, 7.70; S, 4.54. Found: C, 67.86;
H, 7.78; S, 4.37. ESIMS: m/z calcd for [C40H54O7SSi]-
Na+: 729.3250. Found: 729.3252.
3.63. Octyl 4-deoxy-2,3-O-isopropylidene-a-D-lyxo-
hexopyranoside (75)
Prepared from deoxy monosaccharide 74 (237 mg,
0.43 mmol) in THF (12 mL) and TBAF (2.2 mL,
2.2 mmol) as described for 23 to give 75 (97 mg, 72%)
as a colorless oil: Rf 0.27 (3:1 hexane–EtOAc); [a]D
1
+52.1 (c 0.9, CHCl3); H NMR (500 MHz, CDCl3) dH
5.00 (br s, 1H, H-1), 4.39 (ddd, 1H, J = 8.5, 6.0,
6.0 Hz, H-3), 3.97 (d, 1H, J = 6.0 Hz, H-2), 3.80–3.86
(m, 1H, H-5), 3.71 (dt, 1H, J = 9.5, 6.5 Hz, octyl
OCH2), 3.65 (dd, 1H, J = 11.8, 3.5 Hz, H-6a), 3.61
(dd, 1H, J = 11.8, 6.8 Hz, H-6b), 3.43 (dt, 1H, J = 9.5,
6.5 Hz, octyl OCH2), 1.88 (ddd, 1H, J = 13.5, 6.0,
3.8 Hz, H-4eq), 1.54–1.66 (m, 3H, H-4ax, octyl
OCH2CH2), 1.52 (s, 3H, isopropylidene CH3), 1.34 (s,
3H, isopropylidene CH3), 1.22–1.36 (m, 10H, octyl
CH2), 0.88 (t, 3H, J = 7.0 Hz, octyl CH3); 13C NMR
(125 MHz, CDCl3) dC 109.0 (isopropylidene C), 97.7
(C-1), 73.4 (C-2), 70.4 (C-3), 67.9 (octyl OCH2), 66.8
(C-5), 65.7 (C-6), 31.8 (octyl CH2), 29.5 (octyl CH2),
29.4 (octyl CH2), 29.2 (octyl CH2), 29.0 (C-4), 27.9 (iso-
propylidene CH3), 26.2 (octyl CH2), 26.1 (isopropyl-
idene CH3), 22.6 (octyl CH2), 14.1 (octyl CH3). Anal.
Calcd for C17H32O5 (316.22): C, 64.53; H, 10.19. Found:
C, 64.58; H, 10.12. ESIMS: m/z calcd for
[C17H32O5]Na+: 339.2142. Found: 339.2142.
3.62. Octyl 4-deoxy-2,3-O-isopropylidene-6-O-(tert-
butyldiphenylsilyl)-a-D-lyxo-hexopyranoside (74)
Prepared from phenoxythiocarbonyl derivative 73
(398 mg, 0.56 mmol) in toluene (12 mL) and a solution
of tri-n-butylstannane (290 lL, 1.1 mmol) and AIBN
(35 mg, 0.21 mmol) in toluene (50 mL) at reflux as
described for 40 to give 74 (274 mg, 88%) as a colorless
oil: Rf 0.27 (15:1 hexane–EtOAc); [a]D +12.5 (c 2.8,
CHCl3); 1H NMR (500 MHz, CDCl3) dH 7.67–7.72
(m, 4H, ArH), 7.36–7.45 (m, 6H, ArH), 5.04 (s, 1H,
H-1), 4.37 (ddd, 1H, J = 9.5, 6.6, 6.3 Hz, H-3), 3.97
(d, 1H, J = 6.3 Hz, H-2), 3.78–3.84 (m, 1H, H-5),
3.70–3.78 (m, 2H, H-6a, octyl OCH2), 3.62 (dd, 1H,
J = 10.3, 4.8 Hz, H-6b), 3.41 (dt, 1H, J = 9.5, 6.5 Hz,
octyl OCH2), 1.90 (ddd, 1H, J = 13.5, 6.6, 2.3 Hz, H-
4eq), 1.50–1.62 (m, 3H, H-4ax, octyl OCH2CH2), 1.49
(s, 3H, isopropylidene CH3), 1.35 (s, 3H, isopropylidene
CH3), 1.22–1.36 (m, 10H, octyl CH2), 1.07 (s, 9H, tert-
butyl CH3), 0.89 (t, 3H, J = 7.0 Hz, octyl CH3); 13C
NMR (100 MHz, CDCl3) dC 135.6 (4 · Ar), 133.5
3.64. Octyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1!6)-2,3-O-isopropylidene-4-O-methyl-a-D-mannopyr-
anoside (76)
Prepared from thioglycoside 52 (130 mg, 0.19 mmol),
˚
alcohol 72 (54 mg, 0.16 mmol), powdered 4 A molecular
sieves (125 mg), N-iodosuccinimide (54 mg, 0.24 mmol),
and TMSOTf (14 mg, 0.064 mmol) in CH2Cl2 (5 mL)
as described for 31 to give 76 (117 mg, 79%) as a yellow
oil: Rf 0.34 (4:1 hexane–EtOAc); [a]D ꢀ19.0 (c 2.7,
CHCl3); 1H NMR (600 MHz, CDCl3) dH 8.11–8.15
(m, 2H, ArH), 8.04–8.08 (m, 2H, ArH), 7.90–7.94
(m, 2H, ArH), 7.81–7.84 (m, 2H, ArH), 7.56–7.62 (m,
2H, ArH), 7.49–7.53 (m, 1H, ArH), 7.34–7.45 (m, 7H,
ArH), 7.24–7.29 (m, 2H, ArH), 6.14 (dd, 1H, J = 10.2,
10.2 Hz, H-40), 5.94 (dd, 1H, J = 10.2, 3.3 Hz, H-30),
5.73 (dd, 1H, J = 3.3, 1.8 Hz, H-20), 5.19 (d, 1H,