Inter- and intramolecular glycosylation of exo-glycals promoted by metallic Lewis acids

Article abstract of DOI:10.1016/j.carres.2006.04.003

exo-Glycosyl carbonates were employed for inter- and intramolecular glycosylation reactions. A number of metallic Lewis Acids and solvents were examined to enhance the reactivity. The optimum conditions were found to be the use of AlCl₃ in 1-ni

Full text of DOI:10.1016/j.carres.2006.04.003

Carbohydrate Research 341 (2006) 1428–1437
Inter- and intramolecular glycosylation of exo-glycals promoted
by metallic Lewis acids
Sheng-Jie Hsu,a,b Hui-Chang Lina and Chun-Hung Lina,b,
*
aInstitute of Biological Chemistry and Genomics Research Center, Academia Sinica, No. 128 Academia Road Section 2,
Nan-Kang, Taipei 11529, Taiwan
bInstitute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 10617, Taiwan
Received 2 February 2006; received in revised form 18 March 2006; accepted 1 April 2006
Available online 2 May 2006
Abstract—exo-Glycosyl carbonates were employed for inter- and intramolecular glycosylation reactions. A number of metallic
Lewis Acids and solvents were examined to enhance the reactivity. The optimum conditions were found to be the use of AlCl3
in 1-nitropropane. The method was demonstrated to be useful for the intermolecular glycosyl transfer of several nucleophiles,
including simple alcohols, sugars, and amino acid derivatives; however, intramolecular glycosylations were not successful.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Carbonate; exo-Glycal; Glycosylation; Lewis acid; Stereoselectivity
1. Introduction
diation.8 In addition, different reaction routes were
found for the acid-catalyzed glycosylation of exo- and
endo-glycals, where the reaction pathways of rearrange-
ment and protonation were found to compete during the
glycosylation reactions. Interestingly, exo-glycals have a
favored pathway different from their endo-glycal
counterparts.9 As part of our continuing efforts in the
research of glycals, we herein report inter- and intramo-
lecular glycosylation of exo-glycals. Optimization of the
reaction conditions showed that the reaction proceeded
best when done in 1-nitropropane and when the Lewis
acid is AlCl3.
C-glycosylidenes, often referred to as exo-glycals, are
recognized as versatile key intermediates for the prepa-
ration of C-glycosides when the double bond is properly
functionalized with high stereocontrol. Since the first re-
port on exo-glycals appeared thirty years ago,1 extensive
studies have been carried out with two major achieve-
ments in recent years. The first were practical methods
to prepare exo-glycals with a wide range of double bond
substitutions.2–4 The second was to successfully apply
exo-glycals to the synthesis of biologically important
molecules, such as anti-tumor natural products and
enzyme inhibitors.5 These advances have greatly expanded
the availability of these molecules and their uses.
2. Results and discussion
Analogous to the reactions of endo-glycals, exo-gly-
cals have been shown to be reactive glycosyl donors.6
We previously reported that glycosylation of exo-glycals
is applicable to various acceptors with exclusive a-ste-
reo- selectivity. The reactivity can be greatly enhanced
by Ferrier-type rearrangement7 or/and microwave irra-
2.1. Effects of solvent and Lewis acid on glycosylation
In our previous report, exo-glycal carbonate 1 was shown
to be an efficient glycosyl donor using microwave-assisted
glycosylation.8 The same reactions took a much longer
time and gave lower yields with conventional heating
(e.g., in DMF at reflux). The addition of Lewis acids,
such as InCl3 or AlCl3, significantly improved the yields
and reduced the reaction time, which prompted further
*
Corresponding author. Tel.: +886
2 27890110; fax: +886 2
26514705; e-mail: chunhung@gate.sinica.edu.tw
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.04.003

S.-J. Hsu et al. / Carbohydrate Research 341 (2006) 1428–1437
1429
Table 1. Glycosylation of exo-glycal 1 in various solventsa
probably due to resonance and we selected 1-nitropro-
pane for further studies because this solvent afforded the
best yield (80%).
OBn
O
BnO
OH
O
BnO
BnO
O
OBn
O
BnO
Fifteen metallic Lewis acids were then screened as
activators. If the reactions did not proceed or were very
slow, they were kept initially at 0 ꢁC for 1.5 h and the
temperature was raised to 25 ꢁC to finish the reaction.
As shown in Table 2, the majority of reactions gave
the desired products in good yields. The reactions
appear to not have preference for the metal because
Lewis acids derived from alkaline earth metals (Group
IIA), Group IIIB, transition metals, and lanthanides
are all able to promote the reaction, in comparison
with the reaction without a Lewis acid. In particular,
the reactions assisted by AlCl3, SnCl4, Yb(OTf)3, and
Cu(OTf)2 were complete within an hour to provide
70–80% yields. Taking into account reagent cost,
availability, and compatibility with protecting groups,
AlCl3 appeared to be the best choice for additional
investigations.
O
BnO
O
AlCl3
O
O
O
OtBu
O
O
+
O
OBn
O
1
O
O
Solvent
Time (h)
Temperature (ꢁC)
Yield (%)
1-Nitropropane
1-Nitroethane
Nitromethane
CH2Cl2
DMF
THF
0.67
0.67
0.67
0.67
36
40
48
96
0
0
0
80
74
75
68
—
20c
0
b
25
25
25
25
b
Toluene
CH3CN
—
21c
a All reactions were carried out in the presence of AlCl3 (1.0 equiv) and
˚
molecular sieves (4 A). The donor and acceptor were present in a
ratio of 1:1.
b No reaction occurred.
c About a half of the starting material still remained according to TLC.
2.2. Inter- and intramolecular glycosylations
investigations. Table 1 shows the glycosylation of 1,2:3,4-
di-O-isopropylidene-a-galactopyranose by 1 in various
solvents. The reactions in DMF and toluene did not take
place at 25 ꢁC although they indeed occurred at higher
temperatures (e.g., at reflux). Good yields were obtained
when nitroalkanes or dichloromethane was used as the
solvent. We suggest that solvent polarity and basicity
are two main factors playing a role. Because these reac-
tions occur via an oxacarbonium ion intermediate,
solvents of high polarity will help to stabilize the interme-
diate and thus enhance the reactivity.10 The enthalpic
changes of complexation to boron trifluoride are depen-
dent on the solvent and appear in the order: DMF >
THF > CH3CN > CH3NO2 > CH2Cl2.11,12 This analy-
sis is in agreement with our observation that the top three
solvents relatively stabilize Lewis acids and thus the
resulting reactions either do not proceed at all, or proceed
very slowly. Nitroalkanes have low coordinating ability
Using the optimized conditions, exo-glycosyl carbonates
1 and 2 were subjected to glycosylation with several
alcohol nucleophiles, including simple alcohols, sugars,
and amino acid derivatives (Table 3) to give glycoside
products 3–12. Most of the reactions were complete in
40 min and gave moderate to good yields, except for
more hindered substrates (entries iv and ix). The reac-
tions displayed exclusive a-stereoselectivity; that is, all
the nucleophiles attacked from the bottom face of the
sugar ring. This result is consistent with the anomeric
effect because the a-glycoside products are more thermo-
dynamically stable. The product structure and stereo-
chemistry were rigorously determined using DEPT,
NOESY, and other spectroscopic data, in agreement
with previous reports.6–9,13
The use of glycosyl carbonates as donors in glycosyl-
ation reactions14 was first reported by Mukaiyama and
co-workers, where either dimethyl dichlorosilane–silver
Table 2. Effect of Lewis acid on the glycosylation of 1 in 1-nitropropanea
Lewis acid
Time (h)
Temperature (ꢁC)
Yield (%)
Lewis acid
Time (h)
Temperature (ꢁC)
Yield (%)
79
AlCl3
InCl3
ZnCl2
SnCl4
SnCl2
SmCl3
FeCl3
CeCl3
0.67
0
80
82
75
70
75
80
80
Mg(ClO4)2
Mn(CH3CO2)2
Yb(OTf)3
La(OTf)3
Eu(OTf)3
Zn(OTf)2
1.5, 1b
1.5, 28b
0.67
0, 25
0, 25
0
0, 25
0
1.5, 6b
1.5, 1b
0.33
0, 25
0, 25
0
—
c
81
77
80
72
71
1.5, 1.5b
2
2.5
0
1.5, 20
1.5, 6b
1.5,
0, 25
0, 25
0, 25
1.5, 1b
0.67
0, 25
0
Cu(OTf)2
c
—
The reaction is the same as that shown in Table 1 except for the solvent and Lewis acid.
All reactions were carried out in the presence of Lewis acid (1.0 equiv) in 1-nitropropane and molecular sieves (4 A). The donor and acceptor were
a
˚
present in a 1:1 ratio.
b The reaction was initially kept at 0 ꢁC for 1.5 h and the temperature was then raised to 25 ꢁC for the indicated period of time.
c No reaction occurred.

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S.-J. Hsu et al. / Carbohydrate Research 341 (2006) 1428–1437
Table 3. Glycosylations of 1 and 2 with various alcoholsa
perchlorate or tetrakis(pentafluorophenyl)borate was
used as the catalyst.15,16 Excellent b-stereoselectivity
was reported in their studies. A modified version was
developed by Ley et al. to employ 1-imidazolylcarbonyl-
or 1-imidazolylthiocarbonyl glycosides as glycosyl
donors.17,18 In the presence of zinc bromide or silver
perchlorate, the reactions in diethyl ether led to good
a-stereoselectivity, while the use of dichloromethane
resulted in an increase in b-glycosides. The reactions
were promoted by chelation of the metal atom to the
carbonyl oxygen (or thiocarbonyl sulfur) and N3 of
the imidazolyl group. It is interesting that our glycosyl-
ation reactions of exo-glycals generate a-stereoselectiv-
ity exclusively.
OBn
O
OBn
O
X
X
O
O
AlCl3
Y
BnO
Y
BnO
+ ROH
OtBu
C3H7NO2
BnO
OBn
O
R
1, X = OBn, Y = H
2, X = H, Y = OBn
3-12
Entry
Donor
Acceptor
(ROH)
Time
(min)
Product
[yield (%)]
i
1
1
40
3 (86)
OH
ii
40
40
4 (71)
5 (80)
OH
OH
O
O
O
iii
1
Encouraged by these successes, we then turned the
focus to intramolecular glycosylation. Suitable
substrates should contain a donor and an acceptor in
one molecule, that is, the t-butoxy group of carbonates
1 or 2 is replaced with another alcohol. The preparation
of exo-glycal carbonates 13–16 (Fig. 1 and Scheme 1)
was straightforward.19 Compound 17, the precursor of
2, reacted with n-butyl chloroformate to generate 13 in
85% yield, as shown in Scheme 1. Compound 15 was
derived in a similar way from benzyl chloroformate
(82% yield). A two-step procedure is required for the
synthesis of carbonates 14 and 16. The reaction
of methyl 2,3,4-tri-O-methyl-a-D-glucopyranoside with
carbonyl diimidazole (CDI) with a catalytic amount of
KOH afforded 18, which was then coupled with exo-
glycal 17, by treatment with sodium hydride, giving
carbonate 16 in 88% overall yield. Compound 14 was
prepared in an analogous manner in 82% overall yield.
Compounds 13–16 were heated at 125 ꢁC in 1-nitro-
propane to perform the intramolecular glycosylation.
The desired products were obtained in low yields (Table
4). The addition of AlCl3 did not increase the yields, nor
did substitution with other Lewis acids (e.g., BF3ÆOEt2,
or TMSOTf in CH2Cl2). Of the product that was
formed, again, the a-glycosides were produced.
Compound 21 (Fig. 1), which has a free hydroxyl group,
as inspired by Ito’s intramolecular aglycon delivery
using a p-alkoxybenzyl group for tethering,20 was also
O
O
OH
O
MeO
MeO
iv
1
1
1
2
2
90
40
40
40
40
6 (70)
7 (75)
8 (60)
9 (80)
10 (74)
MeO
OMe
OH
v
BocHN
HO
CO2Me
CH3
vi
FmocHN
H3C
CO2Me
O
vii
viii
OH
O
O
O
O
O
OH
O
MeO
MeO
ix
x
2
2
90
40
11 (68)
12 (73)
MeO
OMe
OH
BocHN
CO2Me
a All reactions were carried out in 1-nitropropane with alcohol nucleo-
philes in the presence of molecular sieves (4 A).
˚
OBn
O
OBn
O
O
O
BnO
BnO
BnO
BnO
OC6H13
OC4H9
O
O
OBn
O
OBn
OBn
O
13
14
O
O
BnO
BnO
HO
O
OBn
OBn
O
OBn
O
O
O
O
BnO
BnO
BnO
BnO
O
21
O
MeO
O
OBn
MeO
OBn
MeO
OMe
15
Figure 1. Structures of 13–16 and 21.
16

S.-J. Hsu et al. / Carbohydrate Research 341 (2006) 1428–1437
1431
OBn
O
OBn
O
OH
O
butyl chloroformate
BnO
BnO
BnO
BnO
OC4H9
pyridine
85%
O
OBn
OBn
17
13
O
OH
N
N
O
CDI, KOH
O
MeO
MeO
O
MeO
MeO
toluene
MeO
OMe
MeO
OMe
18
O
OBn
O
O
O
BnO
BnO
17, NaH
O
MeO
DMF
88% (two steps)
MeO
OBn
MeO
OMe
16
Scheme 1. Preparation of 13 and 16.
Table 4. Intramolecular glycosylations of 13–16a
likely causes the low yields of the intramolecular glycosyl
transfer even though the Lewis acid was able to increase
the rate of decarboxylation.ꢀ The molecules used in our
studies should adopt an extended conformation at high
temperature. The longer lifetime of the decomposed
carbonic acid monoester, if such an intermediate exists,
is considered as another plausible cause. Whether there
are other factors involved requires further investigation.
In conclusion, a decarboxylative glycosylation meth-
od that is carried out in AlCl3 in 1-nitropropane has
been developed. The intermolecular reactions could be
applied to a number of alcohol nucleophiles, and prod-
ucts with the a-stereochemistry were formed exclusively
and in good yield. We are further exploring this method-
ology and studies directed at understanding the theoret-
ical basis of this reaction are in progress and will be
published in a due course.
O
O
OBn
O
R
O
OBn
O
BnO
BnO
C3H7NO2
125 oC
BnO
BnO
BnO
O
OBn
13-16
R
Entry
(substrate)
Intramolecular
acceptor (O–R)
Time
(h)
Product
[yield (%)]
i (13)
4
4
2
9 (25)
19 (20)
20 (55)
H3C
H3C
O
ii (14)
O
O
O
iii (15)
O
MeO
iv (16)
4
11 (10)
MeO
MeO
OMe
a All reaction were carried out in 1-nitropropane in the presence of
˚
molecular sieves (4 A).
3. Experimental procedures
3.1. General methods
subjected to the reaction. The formation of the desired
product was still observed in low yield. These unsatisfac-
tory results indicate that the intramolecular glycosyl
transfer is not favored in these reactions.
All reactions were conducted under an argon atmo-
sphere. THF and diethyl ether were distilled from
sodium benzophenone ketyl, CH2Cl2 was distilled from
calcium hydride and CH3OH was distilled from magne-
sium. Solutions of compounds in organic solvents were
dried over Na2SO4 prior to rotary evaporation. DMF
was 99.5% pure and anhydrous. Benzyl bromide was fil-
tered through alumina prior to use. TLC plates (250 lm
of layer thickness) were Kieselgel 60 F254. Carbohydrate
Ikegami et al. have used glycosyl carbonates for intra-
molecular glycosylation,21 and good yields with a- or b-
stereochemical control were achieved by using different
promoters.22,23 In addition, Scheffler and Schmidt
demonstrated with competition experiments that acid-
promoted decarboxylative glycosylation (by using
stoichiometric amount of TMSOTf or TBDMSOTf) fol-
lows an intermolecular course.24 In contrast to these other
studies, there is a longer distance between the donor and
acceptor used in our investigations. The carbonate is
not directly attached to the anomeric center; instead, it
is bridged by two additional carbons. The relative remote-
ness between the anomeric center and the nucleophile
ꢀ In a control experiment that had no Lewis acid, most of the reactant
remained unchanged after the workup. Although the addition of
Lewis acid (e.g., AlCl3, BF3ÆOEt2 or TMSOTf) afforded the desired
product in a similar yield, a significant amount of the rearranged side
product was obtained due to hydration.

1432
S.-J. Hsu et al. / Carbohydrate Research 341 (2006) 1428–1437
compounds were visualized with TLC by the stain solu-
tion p-anisaldehyde/H2SO4/EtOH (6:1:100), phospho-
molybdic acid (PMA)/EtOH (1:20), and H2SO4/EtOH/
H2O (1:10:10). Column chromatography was carried
out with Silica Gel 60 (70–230 mesh); gradients of
EtOAc/hexanes and gradients of CH3OH/CHCl3 were
used as eluents. Optical rotations were measured on a
CH2Ph), 4.75 (1H, d, Ja,b = 11.2 Hz, CH2Ph), 4.73
(1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.68 (1H, d,
Ja,b = 12.8 Hz, CH2Ph), 4.69–4.64 (1H, m, H2b0), 4.65
(1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.61 (1H, d,
Ja,b = 11.6 Hz, CH2Ph), 4.52 (1H, d, Ja,b = 12.4 Hz,
CH2Ph), 4.50 (1H, d, Ja,b = 10.8 Hz, CH2Ph), 3.93
(1H, d, J2,3 = 7.2 Hz, H2), 3.84–3.73 (4H, m, H3, H5,
H6a,b), 3.69 (1H, dd, J4,3 = 6.8 Hz, J4,5 = 7.2 Hz, H4),
1.47 (9H, s, H30 · 9); 13C NMR (CDCl3, 100 MHz): d
153.7, 152.8, 138.3, 138.2, 138.1, 137.8, 128.6, 128.5,
128.4, 128.1, 128.0, 127.9, 127.8, 104.4, 84.7, 82.1,
78.7, 78.4, 77.4, 74.6, 74.5, 73.6, 72.9, 68.5, 61.0, 28.0,
27.9; FABMS: m/z calcd for C41H46O8Na [M+Na]+:
689.3090. Found: 689.3101.
1
digital polarimeter with a cuvette of 10 cm length. H
NMR spectra were recorded at 400 or 500 MHz with
CHCl3 (dH 7.24) or CD3OD [dH 3.30 (central line of a
quintet)] as the internal standard; 13C NMR spectra
were recorded at 100 or 125 MHz with CDCl3 [dC 77.0
(central line of a triplet)] or CD3OD [dC 49.0 (central
line of a septet)] as the internal standard. Mass spectra
were recorded with electrospray (ESI) or fast atom bom-
bardment (FAB) ionization.
3.4. Typical glycosylation procedure (synthesis of 3)
3.2. (Z)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1-O-tert-
butoxycarbonyl-2,3-dideoxy-D-galacto-oct-2-enitol (1)
To a stirred solution of 1 (57 mg, 0.085 mmol) in dry 1-
nitropropane (2 mL) containing 4 A molecular sieves
˚
were added allyl alcohol (17.4 lL, 0.25 mmol) and AlCl3
(11.3 mg, 0.085 mmol) at 0 ꢁC under an argon atmo-
sphere. After 40 min, the reaction mixture was concen-
trated under reduced pressure and the resulting crude
residue was purified by silica gel chromatography with
EtOAc/hexanes (1:10) to give 3 (42 mg, 86% yield) as
a colorless syrup.
To a solution of 17 (1.45 g, 2.55 mmol) in 60 mL dry
DMF were added imidazole-1-carboxylic acid tert-butyl
ester (856 mg, 5.1 mmol) and NaH (255 mg, 6.37 mmol)
at rt, and the solution was stirred for 1 h. Water
(10 mL) was added to quench the reaction and then the
mixture was evaporated under reduced pressure. The
crude residue was extracted by CH2Cl2 and the combined
organic phase was dried (MgSO4), concentrated, and
purified by silica gel chromatography with EtOAc/hex-
anes (1:6) to give 1 (1.528 g, 90%) as a colorless syrup;
Rf 0.23 (1:6, EtOAc/hexanes): [a]D +46.3 (c 1.8, CH2Cl2);
1H NMR (CDCl3, 500 MHz): d 7.34–7.24 (20H, m, ArH),
3.5. Allyl 4,5,6,8-tetra-O-benzyl-1,2-dideoxy-a-D-
galacto-oct-3-ulo-1-enopyranoside (3)
Yield: 86% as a colorless syrup; Rf 0.25 (1:10, EtOAc/
hexanes); 1H NMR (CDCl3, 400 MHz): d 7.36–7.25
(20H, m, ArH), 5.98–5.87 (2H, m, H10, H200), 4.52
5.34 (1H, t, J1 ,2 = 7.5 Hz, H10), 4.90 (1H, d,
Ja,b = 11.5 Hz, CH2Ph), 4.77 (1H, dd, J2a,1 = 8.0,
J2a,2b = 12.0 Hz, H2a0), 4.73 (1H, d, Ja,b = 11.5 Hz,
CH2Ph), 4.70–4.66 (4H, m, CH2Ph), 4.64 (1H, dd,
0
0
(1H, dd, J2a ,1 = 17.6 Hz, J2a ,2b = 1.6 Hz, H2a0), 5.25
0
0
0
0
(1H, dd, J3a ,2 = 11.6 Hz, J3a ,3b = 1.6 Hz, H3a000),
00 00
00
00
0
0
0
0
5.22 (1H, dd, J2b ,1 = 17.6 Hz, J2b ,2a = 1.6 Hz, H2b ),
J2b,1 = 6.0, J2b,2a = 12.0 Hz, H2b0), 4.58 (1H, d, Ja,b
=
5.08 (1H, dd, J3b ,2 = 10.4 Hz, H3b00), 4.95 (1H, d,
00 00
11.5 Hz, CH2Ph), 4.50 (1H, d, Ja,b = 12.0 Hz, CH2Ph),
4.44 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.33 (1H, d,
J2,3 = 8.5 Hz, H2), 4.06 (1H, dd, J4,3 = 2.5 Hz,
Ja,b = 11.6 Hz, CH2Ph), 4.87 (1H, d, Ja,b = 11.2 Hz,
CH2Ph), 4.75 (1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.72
(1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.63 (1H, d,
Ja,b = 11.2 Hz, CH2Ph), 4.60 (1H, d, Ja,b = 11.6 Hz,
CH2Ph), 4.49 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.45
(1H, d, Ja,b = 12.0 Hz, CH2Ph), 3.99–3.83 (5H, m, H2,
H4, H5, H6a, H6b), 3.64–3.55 (2H, m, H1a00, H1b00);
13C NMR (CDCl3, 100 MHz): d 138.9, 138.7, 138.4,
138.1, 135.2, 135.0, 128.3, 128.1, 127.9, 127.6, 127.4,
118.6, 116.2, 100.2, 80.4, 80.3, 75.7, 75.0, 74.4, 73.3,
72.8, 70.4, 69.0, 63.0; FABMS: m/z calcd for
C39H43O6 [M+H]+: 607.3060. Found: 607.3063.
J4,5 = 2.5 Hz, H4), 3.85 (1H, td, J5,4 = 2.5 Hz, J5,6
=
6.0 Hz, H5), 3.73–3.64 (3H, m, H3, H6 · 2), 1.45 (9H, s,
H30 · 9); 13C NMR (CDCl3, 100 MHz): d 153.5, 138.4,
138.3, 137.9, 128.4, 128.3, 128.2, 127.9, 127.8, 127.7,
127.6, 127.5, 127.4, 105.0, 81.7, 78.2, 76.5, 74.3, 74.2,
73.6, 73.4, 72.8, 68.3, 61.0, 60.3, 27.7; FABMS: m/z calcd
for C41H46O8Na [M+Na]+: 689.3090. Found: 689.3089.
3.3. (Z)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1-O-tert-
butoxycarbonyl-2,3-dideoxy-D-gluco-oct-2-enitol (2)
3.6. Isopropyl 4,5,6,8-tetra-O-benzyl-1,2-dideoxy-a-D-
galacto-oct-3-ulo-1-enopyranoside (4)
The compound was prepared in the same manner as 1.
[a]D +47.3 (c 2.4, CH2Cl2); 1H NMR (CDCl3,
400 MHz): d 7.33–7.12 (20H, m, ArH), 5.22 (1H, t,
Yield: 71% as a colorless syrup; Rf 0.31 (1:6, EtOAc/hex-
anes); 1H NMR (CDCl3, 400 MHz): d 7.35–7.23 (20H, m,
J1 ,2 = 7.6 Hz, H10), 4.82 (1H, dd, J2a ,1 = 7.6 Hz,
0
0
0
0
J2a ,2b = 12.4 Hz, H2a0), 4.81 (1H, d, Ja,b = 11.6 Hz,
ArH), 6.03 (1H, dd, J1 ,2a = 17.6 Hz, J1 ,2b = 10.8 Hz,
0
0
0
0
0
0

S.-J. Hsu et al. / Carbohydrate Research 341 (2006) 1428–1437
1433
H10), 5.53 (1H, dd, J2a ,1 = 17.6 Hz, J2a ,2b = 2.0 Hz,
400 MHz): d 7.35–7.24 (20H, m, ArH), 5.92 (1H, dd,
0
0
0
0
H2a0), 5.19 (1H, dd, J2b ,1 = 10.8 Hz, J2b ,2a = 2.0 Hz,
H2b0), 4.94 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.91 (1H, d,
Ja,b = 12.0 Hz, CH2Ph), 4.75 (1H, d, Ja,b = 12.0 Hz,
CH2Ph), 4.72 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.62 (1H,
d, Ja,b = 11.6 Hz, CH2Ph), 4.60 (1H, d, Ja,b = 11.6 Hz,
CH2Ph), 4.51 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.46 (1H,
d, Ja,b = 12.0 Hz, CH2Ph), 4.09–4.03 (3H, m, H3, H4,
H5), 3.95 (1H, m, H100), 3.78 (1H, d, J2,3 = 9.6 Hz, H2),
3.66 (1H, dd, J6a,6b = 9.2 Hz, J6a,5 = 7.6 Hz, H6a), 3.58
(1H, d, J6b,6a = 9.2 Hz, J6b,5 = 5.6 Hz, H6b), 1.16 (3H,
d, J = 2.4 Hz, CH3), 1.15 (3H, d, J = 2.8 Hz, CH3); 13C
NMR (CDCl3, 100 MHz): d 139.1, 138.8, 138.2, 136.6,
128.3, 128.2, 128.1, 127.9, 127.8, 127.6, 127.4, 127.3,
117.4, 100.2, 81.2, 80.4, 75.5, 74.8, 74.4, 73.4, 72.6, 70.3,
69, 65.3, 24.1, 23.6; FABMS: m/z calcd for C39H45O6
[M+H]+: 609.3216. Found: 609.3219.
J1 ,2a = 17.6 Hz, J1 ,2b = 10.8 Hz, H10), 5.52 (1H, dd,
0
0
0
0
0
0
0
0
J2a ,1 = 17.6 Hz, J2a ,2b = 2.0 Hz, H2a0), 5.26 (1H, dd,
0
0
0
0
J2b ,1 = 10.8 Hz, J2b ,2a = 2.0 Hz, H2b0), 4.96 (1H, d,
Ja,b = 11.6 Hz, CH2Ph), 4.88 (1H, d, Ja,b = 11.6 Hz,
CH2Ph), 4.69–4.60 (5H, m, H100, CH2Ph), 4.50 (1H, d,
Ja,b = 11.6 Hz, CH2Ph), 4.45 (1H, d, Ja,b = 12.4 Hz,
CH2Ph), 4.07 (1H, m, H5), 4.03 (1H, dd, J3,2 = 9.6 Hz,
J3,4 = 2.8 Hz, H3), 3.96 (1H, m, H4), 3.84 (1H, d,
J2,3 = 10 Hz, H2), 3.69–3.56 (4H, m, H200, H300, H400,
H500), 3.58 (3H, s, OCH3), 3.48–3.44 (4H, m, H6,
OCH3), 3.42 (3H, s, OCH3), 3.35 (1H, dd,
J6a,6b = 10.8 Hz, J6a,5 = 7.6 Hz, H6), 3.32 (3H, s,
0
0
0
0
0
0
00 00
OCH3), 3.10 (1H, dd, J6a ,6b = 9.6 Hz, J6a ,5 = 3.6 Hz,
H6a00), 2.90 (1H, dd, J6b ,6a = 10.0 Hz, J6b ,5 = 8.8 Hz,
H6b00); 13C NMR (CD2Cl2, 100 MHz): d 139, 138.7,
138.6, 138.3, 135.2, 128.3, 128.1, 128, 127.9, 127.5,
127.4, 127.3, 118.4, 99.8, 96.8, 83.5, 81.8, 80.5, 79.7,
75.2, 75.1, 74.4, 73.1, 72.5, 70.1, 69.7, 69.0, 61.4, 60.7,
60.2, 58.8, 54.7; FABMS: m/z calcd for C46H57O11
[M+H]+: 785.3901. Found: 785.3898.
00
00
00 00
3.7. 4,5,6,8-Tetra-O-benzyl-1,2-dideoxy-a-D-galacto-oct-
3-ulo-1-enopyranosyl-(3!6)-1,2:3,4-diisopropylidine-
a-D-galactopyranose (5)
Yield: 80% as a colorless syrup; Rf 0.33 (1:3, EtOAc/
hexanes); [a]D +8.1 (c 2.5, CH2Cl2); H NMR (CDCl3,
400 MHz): d 7.35–7.23 (20H, m, ArH), 5.95 (1H, dd,
3.9. O-(4,5,6,8-Tetra-O-benzyl-1,2-dideoxy-a-D-galacto-
oct-3-ulo-1-enopyranosyl)-N-tert-butoxycarbonyl-L-
serine methyl ester (7)
1
J1 ,2a = 17.6 Hz, J1 ,2b = 11.2 Hz, H10), 5.52 (1H, dd,
0
0
0
0
0
0
0
0
0
J2a ,1 = 17.6 Hz, J2a ,2b = 2.0 Hz, H2a ), 5.48 (1H, d,
Yield: 75% as a colorless syrup; Rf 0.27 (1:4, EtOAc/
1
J1 ,2 = 4.8 Hz, H100), 0 5.23 (1H, dd, J2b ,1 = 11.2 Hz,
hexanes); [a]D +18 (c 2.2, CH2Cl2); H NMR (CDCl3,
00 00
0
0
0
0
J2b ,2a = 2.0 Hz, H2b ), 4.92 (1H, d, Ja,b = 11.6 Hz,
CH2Ph), 4.87 (1H, d, Ja,b = 11.2 Hz, CH2Ph), 4.71 (2H,
s, CH2Ph), 4.61 (1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.60
(1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.55 (1H, dd,
400 MHz): d 7.33–7.21 (20H, m, ArH), 5.81 (1H, dd,
J1 ,2a = 10.8 Hz, J1 ,2b = 17.6 Hz, H10), 5.49 (1H, dd,
0
0
0
0
J2a ,1 = 17.2 Hz, J2a ,2b = 1.2 Hz, H2a0), 5.37 (1H, d,
0
0
0
00
0
0
J = 8.4 Hz, NH), 5.28 (1H, dd, J2b ,2a = 1.6 Hz,
J3 ,2 = 8.0 Hz, J3 ,4 = 2.4 Hz, H300), 4.51 (1H, d,
Ja,b = 11.6 Hz, CH2Ph), 4.45 (1H, d, Ja,b = 12.0 Hz,
CH2Ph), 4.27–4.23 (2H, m, H200, H400), 4.16 (1H, m,
H5), 4.10 (1H, dd, J3,2 = 10.0 Hz, J3,4 = 3.2 Hz, H3),
4.02 (1H, dd, J4,3 = 3.2 Hz, J4,5 = 1.2 Hz, H4), 3.98
(1H, m, H500), 3.84 (1H, d, J2,3 = 10 Hz, H2), 3.68 (1H,
dd, J6a,6b = 9.2 Hz, J6a,5 = 8.0 Hz, H6a), 3.61 (1H,
J2b ,1 = 11.2 Hz, H2b0), 4.92 (1H, d, Ja,b = 11.6 Hz,
CH2Ph), 4.86 (1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.71
(2H, s, CH2Ph), 4.58 (1H, d, Ja,b = 12 Hz, CH2Ph),
4.53 (1H, d, Ja,b = 11.2 CH2Ph), 4.50–4.42 (3H, m,
H200, CH2Ph · 2), 3.98–3.96 (2H, m, H2, H3), 3.86–
3.75 (3H, m, H4, H5, H6), 3.59 (3H, s, COOCH3),
3.57–3.51 (3H, m, H6, H1a00,b00), 1.42 (9H, s, 3CH3);
13C NMR (CDCl3, 100 MHz): d 171.0, 138.9, 138.8,
138.6, 138, 134.5, 128.3, 128.1, 127.9, 127.7, 127.6,
127.5, 127.4, 127.2, 119.3, 99.9, 80.5, 79.7, 75.2, 74.7,
74.5, 73.4, 72.6, 70.5, 68.8, 62.4, 53.9, 52.2, 28.3;
FABMS: m/z calcd for C45H53O10Na [M+Na]+:
790.3576. Found: 790.3574.
00 00
00 00
0
0
dd, J6a ,6b = 10.8, J6a ,5 = 5.2 Hz, H6a00), 3.56 (1H, dd,
J6b,6a = 9.2 Hz, J6b,5 = 5.6 Hz, H6b), 3.50 (1H, dd,
00
00
00 00
J6b ,6a = 10.8 Hz, J6b ,5 = 6.8 Hz, H6b00), 1.49 (3H, s,
CH3), 1.38 (3H, s, CH3), 1.30 (6H, s, 2CH3); 13C NMR
(CDCl3, 100 MHz): d 139.1, 138.8, 138.7, 138.3, 135.3,
128.3, 128.2, 128.1, 128, 127.9, 127.7, 127.5, 127.4,
127.3, 118.7, 109.1, 108.4, 99.9, 96.2, 80.5, 80.2, 75.3, 75,
74.5, 73.1, 72.6, 71.3, 70.7, 69.7, 68.6, 67.3, 61.3, 26.1,
25.9; FABMS: m/z calcd for C48H57O11 [M+H]+:
809.3901. Found: 809.3906.
00
00
00 00
3.10. O-(4,5,6,8-Tetra-O-benzyl-1,2-dideoxy-a-D-
galacto-oct-3-ulo-1-enopyranosyl)-N-a-(9-fluorenylmeth-
yloxycarbonyl)-L-threonine methyl ester (8)
3.8. Methyl 4,5,6,8-tetra-O-benzyl-1,2-dideoxy-a-D-
galacto-oct-3-ulo-1-enopyranosyl-(3!6)-2,3,4-tri-O-
methyl-a-D-glucopyranoside (6)
Yield: 60% as a white solid; Rf 0.2 (1:5, EtOAc/hexanes);
1H NMR (CDCl3, 400 MHz): d 7.74 (2H, d, J = 7.6 Hz,
ArH), 7.60 (2H, dd, J = 2.8, 7.2 Hz, ArH), 7.37–7.21
0
0
(24H, m, ArH), 5.87 (1H, dd, J1 ,2a = 11.2 Hz,
0
0
Yield: 70% as a colorless syrup; Rf 0.26 (1:2.5, EtOAc/
hexanes); [a]D +54.5 (c 1.8, CH2Cl2); 1H NMR (CDCl3,
J1 ,2a = 17.6 Hz, H10), 5.71 (1H, d, J = 9.2 Hz, NH),
5.59 (1H, dd, J2a ,2b = 1.6 Hz, J2a ,1 = 17.6 Hz, H2a0),
0
0
0
0

1434
S.-J. Hsu et al. / Carbohydrate Research 341 (2006) 1428–1437
5.31 (1H, dd, J2b ,2a = 1.6 Hz, J2b ,1 = 10.8 Hz, H2b0),
4.95 (1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.87 (1H, d,
Ja,b = 10.8 Hz, CH2Ph), 4.75 (2H, s, CH2Ph), 4.61
(1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.54 (1H, d,
Ja,b = 11.2 Hz, CH2Ph), 4.50–4.33 (4H, m, H200,
H4a00,4b00, CH2Ph), 4.26–4.23 (2H, m, H300, H500), 4.05–
3.98 (3H, m, H3, H4, H5), 3.76 (1H, d, J2,3 = 9.6 Hz,
H2), 3.64 (1H, dd, J6a,5 = 7.2 Hz, J6a,6b = 9.2 Hz,
H6a), 3.54 (1H, dd, J6b,5 = 6 Hz, J6b,6a = 9.2 Hz, H6b),
3.45 (3H, s, COOCH3), 1.61 (3H, d, J = 6.4 Hz CH3);
13C NMR (CDCl3, 100 MHz): d 170.8, 156.7, 144.0,
143.8, 141.2, 138.9, 138.5, 138.0, 134.4, 128.4, 128.3,
128.1, 127.8, 127.7, 127.6, 127.5, 127.4, 127.1, 127.0,
125.1, 119.9, 119.0, 100.3, 81.0, 79.6, 75.7, 74.7, 74.4,
73.5, 72.5, 70.4, 69.8, 68.8, 67.1, 59.5, 52.1, 47.2, 18.7;
FABMS: m/z calcd for C56H58NO10 [M+H]+:
904.4061. Found: 904.4056.
m, H300, CH2Ph · 4), 4.30 (1H, dd, J2 ,3 = 8 Hz,
0
0
0
0
00 00
J2 ,1 = 2 Hz, H200), 4.26 (1H, dd, J4 ,3 = 5.2 Hz,
00 00
00 00
J4 ,5 = 2.4 Hz, H400), 4.10 (1H, dd, J3,2 = 9.2 Hz,
00 00
J3,4 = 9.2 Hz, H3), 3.98 (1H, m, H500), 3.92 (1H, m,
H5), 3.82 (1H, dd, J6a,6b = 11.2 Hz, J6a,5 = 3.6 Hz,
H6a), 3.73–3.64 (3H, m, H6b, H6a00, H6b00), 3.5 (1H,
dd, J4,3 = 10.0 Hz, J4,5 = 5.6 Hz, H4), 3.35 (1H, d,
J2,3 = 9.2 Hz, H2), 1.66 (3H, s, CH3), 1.40 (3H, s,
CH3), 1.31 (3H, s, CH3), 1.30 (3H, s, CH3); 13C NMR
(CDCl3, 100 MHz): d 138.8, 138.6, 138.4, 135.6, 128.3,
128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4,
118.8, 109, 108.5, 99.8, 96.2, 84.6, 82.7, 78.4, 75.4,
74.5, 73.3, 71.5, 71.1, 70.7, 70.6, 68.8, 67.5, 67.1, 61.2,
26.1, 25.9, 24.9, 24.4; FABMS: m/z calcd for
C48H57O11 [M+H]+: 809.3901. Found: 809.3908.
3.13. Methyl 4,5,6,8-tetra-O-benzyl-1,2-dideoxy-a-D-
gluco-oct-3-ulo-1-enopyranosyl-(3!6)-2,3,4-tri-O-
methyl-a-D-glucopyranoside (11)
3.11. n-Butyl 4,5,6,8-tetra-O-benzyl-1,2-dideoxy-a-D-
gluco-oct-3-ulo-1-enopyranoside (9)
Yield: 68% as a colorless syrup; [a]D +84.5 (c 1.9,
CH2Cl2); 1H NMR (CD2Cl2, 400 MHz): d 7.41–7.26
Yield: 80% as a colorless syrup; Rf 0.24 (1:15, EtOAc/
hexanes); 1H NMR (CD2Cl2, 400 MHz): d 7.46–7.33
0
0
(20H, m, ArH), 6.04 (1H, dd, J1 ,2a = 11.2 Hz,
0
0
0
0
0
0
(20H, m, ArH), 5.99 (1H, dd, J1 ,2a = 10.8 Hz,
J1 ,2b = 17.6 Hz, H10), 5.63 (1H, dd, J2b ,2a = 1.6 Hz,
J1 ,2b = 17.6 Hz, H10), 5.54 (1H, dd, J2b ,2a = 2.0 Hz,
J2b ,1 = 17.2 Hz, H2b0), 5.42 (1H, dd, J2a ,2b = 2.0 Hz,
0
0
0
0
0
0
0
0
J2b ,1 = 17.6 Hz, H2b0), 5.35 (1H, dd, J2a ,2b = 2.0 Hz,
J2a ,1 = 10.8 Hz, H2a0), 4.94 (1H, d, Ja,b = 10.8 Hz,
CH2Ph), 4.91 (1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.88
(1H, d, Ja,b = 10.8 Hz, CH2Ph), 4.87 (1H, d,
0
0
0
0
0
0
J2a ,1 = 10.8 Hz, H2a0), 4.98 (1H, d, Ja,b = 11.2 Hz,
CH2Ph), 4.89 (1H, d, Ja,b = 10.8 Hz, CH2Ph), 4.84
(1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.79 (1H, d,
Ja,b = 11.6 Hz, CH2Ph), 4.62 (1H, d, Ja,b = 10.4 Hz,
CH2Ph), 4.61 (1H, d, Ja,b = 11.2 Hz, CH2Ph), 4.60
(1H, d, Ja,b = 12.0 Hz, CH2Ph), 5.54 (1H, d,
Ja,b = 12.0 Hz, CH2Ph), 4.13–4.08 (2H, m, H3, H5),
3.94 (1H, dd, J4,3 = 6.0 Hz, H4), 3.80 (1H, d,
J2,3 = 9.6 Hz, H2), 3.71 (1H, dd, J6a,5 = 7.2 Hz,
J6a,6b = 9.6 Hz, H6a), 3.65 (1H, dd, J6b,5 = 6.0 Hz,
J6b,6a = 9.2 Hz, H6b), 3.44–3.31 (2H, m, H1a00, H1b00),
1.62–1.56 (2H, m, H2a00, H2b00), 1.43–1.34 (2H, m,
H3a00, H3b00), 0.96 (3H, t, J = 11.6 Hz, CH3); 13C
NMR (CD2Cl2, 100 MHz): d 138.9, 138.8, 138.6,
138.3, 135.6, 128.2, 128.1, 128, 127.5, 127.4, 127.3,
117.9, 99.5, 80.7, 80.1, 75.6, 75.2, 74.7, 73.2, 72.5, 70.1,
69, 61.2, 31.7, 29.6, 19.5, 13.7, 10.7; FABMS: m/z calcd
for C40H46NaO6 [M+Na]+: 645.3192. Found: 645.3195.
0
0
00 00
Ja,b = 11.2 Hz, CH2Ph), 4.80 (1H, d, J1 ,2 = 3.6 Hz,
H100), 4.67 (1H, d, Ja,b = 10.0 Hz, CH2Ph), 4.68 (1H,
d, Ja,b = 12.0 Hz, CH2Ph), 4.64 (1H, d, Ja,b = 10.4 Hz,
CH2Ph), 4.61 (1H, d, Ja,b = 13.2 Hz, CH2Ph), 4.1 (1H,
dd, J3,2 = 9.2 Hz, J3,4 = 9.6 Hz, H3), 4.02 (1H, ddd,
J5 ,4 = 1.6 Hz, J5 ,6a = 4.0 Hz, J5 ,6b = 10.0 Hz, H500),
3.84–3.37 (8H, m, H3, H4, H5, H6A, H6B, H400,
H600A, H600B), 3.60 (3H, s, OCH3), 3.52 (3H, s,
OCH3), 3.47 (3H, s, OCH3), 3.40 (3H, s, OCH3), 3.20
00 00
00
00
00
00
(1H, dd, J2 ,1 = 4.0 Hz, J2 ,3 = 10.4 Hz, H200), 3.03
00 00
00 00
(1H, dd, J3 ,4 = 8.8 Hz, J3 ,2 = 10.0 Hz, H300); 13C
NMR (CD2Cl2, 100 MHz): d 138.8, 138.6, 138.2,
135.3, 128.2, 128.1, 128, 127.9, 127.8, 127.6, 127.5,
127.4, 127.3, 127.2, 118.5, 99.2, 96.8, 84.5, 83.5, 82.7,
81.7, 79.7, 78.4, 75.5, 75.1, 74.4, 73, 71.2, 69.4, 68.9,
61, 60, 59.9, 58.1, 54.0; FABMS: m/z calcd for
C46H56O11 [M+H]+: 785.3901. Found: 785.3905.
00 00
00 00
3.12. 4,5,6,8-Tetra-O-benzyl-1,2-dideoxy-a-D-gluco-oct-3-
ulo-1-enopyranosyl-(3!6)-1,2:3,4-diisopropylidine-a-D-
galactopyranose (10)
3.14. O-(4,5,6,8-Tetra-O-benzyl-1,2-dideoxy-a-D-gluco-
oct-3-ulo-1-enopyranosyl)-N-tert-butoxycarbonyl-L-
serine methyl ester (12)
Yield: 74% as a colorless syrup; [a]D +5.0 (c 2.2,
CH2Cl2); 1H NMR (CDCl3, 400 MHz): d 7.34–7.2
Yield: 73% as a colorless syrup; [a]D +54 (c 1.4, CHCl3);
1H NMR (CDCl3, 400 MHz): d 7.35–7.19 (20H, m,
0
0
(20H, m, ArH), 5.99 (1H, dd, J1 ,2a = 17.2 Hz,
J1 ,2b = 10.8 Hz, H10), 5.58 (1H, dd, J2a ,1 = 17.2 Hz,
ArH), 5.82 (1H, dd, J1 ,2a = 11.6 Hz, J1 ,2b = 17.6 Hz,
0
0
0
0
0
0
0
0
J2a ,2b = 2.0 Hz, H2a0), 5.48 (1H, d, J1 ,2 = 4.8 Hz,
H100), 5.28 (1H, dd, J2b ,1 = 10.8 Hz, J2b ,2a = 2.0 Hz,
H2b0), 4.88–4.81 (4H, m, CH2Ph · 4), 4.66–4.53 (5H,
H10), 5.55 (1H, dd, J2b ,2a = 1.6 Hz, J2b ,1 = 17.6 Hz,
H2b0), 5.42 (1H, d, J = 8.0 Hz, NH), 5.33 (1H, dd,
J2a ,2b = 1.6 Hz, J2a ,1 = 10.8 Hz, H2a0), 4.85–4.79
0
0
00 00
0
0
0
0
0
0
0
0
0
0
0
0

S.-J. Hsu et al. / Carbohydrate Research 341 (2006) 1428–1437
1435
(4H, m, CH2Ph · 4), 4.65–4.52 (4H, m, CH2Ph · 4), 4.45
(1H, d, J = 8.4 Hz, H200), 4.02 (1H, dd, J3,2 = 8.8 Hz,
purified by silica gel chromatography (1:5, EtOAc/hex-
anes) to give 14 (183 mg, 98%) as a colorless syrup; Rf
0.33 (1:5, EtOAc/hexanes); [a]D +36.7 (c 3.1, CHCl3);
1H NMR (CDCl3, 400 MHz): d 7.35–7.13 (20H, m,
00 00
J3,4 = 9.2 Hz, H3), 3.85 (1H, dd, J1a ,2 = 2.4 Hz,
J1a ,1b = 10.0 Hz, H1a00), 3.77 (1H, m, H6), 3.70–3.66
(3H, m, H4, H5, H6), 3.64 (3H, s, COOCH3), 3.55
00
00
0
0
0
0
ArH), 5.22 (1H, dd, J1 ,2a = 6.8 Hz, J1 ,2b = 6.8 Hz,
(1H, dd, J1b ,2 = 3.2 Hz, J1b ,1a = 10 Hz, H1b00), 3.32
(1H, d, J2,3 = 9.6 Hz, H2), 1.42 (9H, s, 3CH3); 13C
NMR (CDCl3, 100 MHz): d 171.1, 155.6, 138.9, 138.7,
138.5, 134.9, 128.7, 128.5, 128.4, 128.2, 128.1, 128,
127.9, 127.8, 127.7, 127.6, 127.5, 127.1, 119.5, 99.6,
84.6, 82.8, 78.4, 75.6, 75.4, 75.1, 73.6, 72.2, 68.8, 62.4,
54.0, 52.5, 28.5; FABMS: m/z calcd for C45H53O10Na
[M+Na]+: 790.3576. Found: 790.3553.
H10), 4.91 (1H, dd, J2a ,1 = 6.8 Hz, J2a ,2b = 12 Hz,
H2a0), 4.81 (1H, d, Ja,b = 11.2 Hz, CH2Ph), 4.76 (1H,
d, Ja,b = 11.2 Hz, CH2Ph), 4.73 (1H, d, Ja,b = 11.6 Hz,
CH2Ph), 4.72–4.70 (1H, m, H20), 4.69 (1H, d,
Ja,b = 11.2 Hz, CH2Ph), 4.64 (1H, d, Ja,b = 12.0 Hz,
CH2Ph), 4.61 (1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.52
(1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.51 (1H, d,
Ja,b = 10.8 Hz, CH2Ph), 4.11 (2H, d, J = 6.8 Hz,
H3a0,3b0), 3.94 (1H, d, J2,3 = 6.8 Hz, H2), 3.84–3.68
(5H, m, H3, H4, H5, H6a,b), 1.68–1.61 (2H, m,
H4a0,b0), 1.39–1.25 (6H, H5a0,b0, H6a0,b0, H7a0,b0),
00 00
00
00
0
0
0
0
3.15. (Z)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1-O-n-
butoxycarbonyl-2,3-dideoxy-D-gluco-oct-2-enitol (13)
0.88 (3H, t, J8 ,7 = 6.8 Hz, H80 · 3); 13C NMR (CDCl3,
100 MHz): d 55.5, 153.3, 138.3, 138.2, 138.1, 137.8,
128.6, 128.5, 128.1, 128, 127.9, 127.8, 104.1, 84.7, 78.8,
78.5, 77.4, 74.6, 74.5, 73.7, 73, 68.6, 68.3, 61.8, 31.6,
28.8, 25.5, 22.7, 14.2; FABMS: m/z calcd for
C43H50O8 [M+H]+: 694.3506. Found: 694.3497.
0
0
To a solution of 17 (630 mg, 1.11 mmol) in dry CH2Cl2
(10 mL) was added butyl chloroformate (2.22 mL,
2.22 mmol) and pyridine (447 lL, 5.55 mmol) under
Ar atmosphere at rt. After 20 min, the reaction mixture
was concentrated under reduced pressure to give a resi-
due that was purified by silica gel chromatography (1:6,
EtOAc/hexanes) to give 13 (628 mg, 85%) as a colorless
3.17. (Z)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1-O-benz-
yloxycarbonyl-2,3-dideoxy-D-gluco-oct-2-enitol (15)
1
syrup; Rf 0.27; [a]D +40.4 (c 2.6, CH2Cl2); H NMR
(CD2Cl2, 500 MHz): d 7.37–7.21 (20H, m, ArH), 5.17
(1H, t, J1 ,2 = 7.0 Hz, H10), 4.86 (1H, dd,
The preparation was similar to that of compound 13.
Yield: 82% as a colorless syrup; [a]D +44 (c 6.1,
CH2Cl2); 1H NMR (CD2Cl2, 500 MHz): d 7.38–7.18
(25H, m, ArH), 5.31–5.30 (2H, m, CH2Ph · 2), 5.15–
0
0
0
0
0
0
0
J2a ,1 = 7.5 Hz, J2a ,2b = 12.0 Hz, H2a ), 4.79 (1H, d,
Ja,b = 12.5 Hz, CH2Ph), 4.77–4.71 (3H, m, CH2Ph · 2,
H20), 4.69 (1H, d, Ja,b = 11 Hz, CH2Ph), 4.63 (1H, d,
Ja,b = 12.5 Hz, CH2Ph), 4.61 (1H, d, Ja,b = 12.0 Hz,
CH2Ph), 4.57 (1H, d, Ja,b = 11.5 Hz, CH2Ph), 4.57
(1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.13 (2H, t,
J3 ,4 = 7.0 Hz, H30), 3.97 (1H, d, J2,3 = 6.0 Hz, H2),
3.93 (1H, ddd, J5,4 = 2.0 Hz, J5,6a = 4.0 Hz,
J5,6b = 9.5 Hz, H5), 3.83 (1H, dd, J6a,5 = 1.5 Hz,
J6a,6b = 11.0 Hz, H6a), 3.81–3.73 (3H, m, H3, H4,
H6), 1.66 (2H, m, H4a0, H4b0), 1.41 (2H, m, H5a0,
5.12 (1H, m, H10), 4.85 (1H, dd, J2a ,1 = 7.5 Hz,
0
0
J2a ,2b = 12 Hz, H2a0), 4.75 (1H, d, Ja,b = 11.5 Hz,
CH2Ph), 4.73–4.70 (1H, m, H20), 4.70 (2H, d,
Ja,b = 12.0 Hz, CH2Ph), 4.65 (1H, d, Ja,b = 11.5 Hz,
CH2Ph), 4.59 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.56
(1H, d, Ja,b = 11.5 Hz, CH2Ph), 4.53 (1H, d,
Ja,b = 11.0 Hz, CH2Ph), 4.52 (1H, Ja,b = 12.0 Hz,
CH2Ph), 3.93 (1H, d, J2,3 = 6.0 Hz, H2), 3.88 (1H,
ddd, J5,4 = 2.0 Hz, J5,6a = 4.0 Hz, J5,6b = 10.0 Hz, H5),
3.78 (1H, dd, J6a,5 = 4.0 Hz, J6a,6b = 12.0 Hz, H6a),
3.76–3.71 (2H, m, H4, H6b), 3.70 (1H, dd,
J3,2 = 6.5 Hz, J3,4 = 6.5 Hz, H3); 13C NMR (CD2Cl2,
100 MHz): d 155.4, 153.6, 138.7, 138.6, 138.2, 128.8,
128.7, 128.6, 128.5, 128.3, 128.2, 128.1, 128, 127.9,
103.9, 84.2, 78.6, 78.2, 77.8, 74.3, 74, 73.7, 72.5, 69.7,
69.2, 62.1; FABMS: m/z calcd for C44H44O8Na
[M+Na]+: 723.2934. Found: 723.2919.
0
0
0
0
H5b0), 0.95 (3H, t, J6 ,5 = 7.5 Hz, H60 · 3); 13C NMR
(CD2Cl2, 125 MHz): d 155.6, 153.2, 138.7, 138.2,
128.7, 128.6, 128.5, 128.3, 128.2, 128.1, 128, 127.9,
104.1, 84.3, 78.7, 78.2, 77.9, 77.8, 74.3, 74.0, 73.7, 72.6,
69.2, 68.0, 61.8, 31.1, 19.3, 13.8; FABMS: m/z calcd
for C41H46O8 [M+H]+: 666.3193. Found: 666.3186.
0
0
3.16. (Z)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1-O-n-hex-
oxycarbonyl-2,3-dideoxy-D-gluco-oct-2-enitol (14)
To a stirred solution of 17 (154 mg, 0.27 mmol) in dry
DMF (5 mL) were added 1,10-carbonyl-n-hexanoxy-
imidazole (106 mg, 0.54 mmol) and NaH (21.6 mg,
0.54 mmol) under an argon atmosphere at rt. After
1 h, H2O was added to quench the reaction and the sol-
vent was removed under reduced pressure. The crude
product was extracted by CH2Cl2 and the combined
organic phase was dried (MgSO4), concentrated, and
3.18. (Z)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-2,3-di-
deoxy-1-O-[(methyl 2,3,4-tri-O-methyl-a-D-glucopyran-
oside-6-O-yl)carbonyl]-D-gluco-oct-2-enitol (16)
To a stirred solution of 17 (128 mg, 0.27 mmol) in dry
DMF (5 mL) were added 18 (112 mg, 0.34 mmol) and
NaH (21.6 mg, 0.54 mmol) under an argon atmosphere
at rt. After 1 h, the reaction was quenched by the

1436
S.-J. Hsu et al. / Carbohydrate Research 341 (2006) 1428–1437
addition of water and then concentrated under reduced
pressure. The crude product was extracted by CH2Cl2
and the combined organic phase was dried (MgSO4),
concentrated, and purified by silica gel chromatography
(1:1, EtOAc/hexanes) to give 16 (185 mg, 88%) as a
colorless syrup; Rf 0.4 (1:1, EtOAc/hexanes); [a]D +92
128, 127.9, 127.8, 127.7, 118.5, 84.7, 83.2, 78.7, 77.4,
75.8, 75.7, 75.2, 73.5, 71.9, 69.0, 62.0, 31.8, 29.8, 26.1,
22.8; FABMS: m/z calcd for C42H50O6Na [M+Na]+:
673.3505. Found 673.3505.
3.20. Benzyl 4,5,6,8-tetra-O-benzyl-1,2-dideoxy-a-D-
gluco-oct-3-ulo-1-enopyranoside (20)
1
(c 1.0, CHCl3); H NMR (CDCl3, 500 MHz): d 7.32–
0
0
7.12 (20H, m, ArH), 5.19 (1H, dd, J1 ,2a = 7.0 Hz,
J1 ,2b = 7.5 Hz, H10), 4.92 (1H, dd, J2b ,1 = 8.0 Hz,
A stirred solution of 15 (55 mg, 0.078 mmol) in dry 1-
nitropropane (2 mL) was heated at 125 ꢁC for 2 h. The
solvent was then removed under reduced pressure yield-
ing a residue that was purified by silica gel chromatogra-
phy (1:10, EtOAc/hexanes) to give 20 (28 mg, 55%) as a
colorless syrup; Rf 0.24 (1:10, EtOAc/hexanes); 1H
NMR (CD2Cl2, 500 MHz): d 7.35–7.22 (25H, m,
0
0
0
0
J2b ,2a = 12.5 Hz, H2b0), 4.78 (1H, d, Ja,b = 12.0 Hz,
0
0
CH2Ph), 4.77 (1H, d, J3 ,4 = 4.0 Hz, H30), 4.74 (1H, d,
Ja,b = 11.0 Hz, CH2Ph), 4.70 (1H, d, Ja,b = 11.5 Hz,
CH2Ph), 4.71 (1H, m, H20), 4.67 (1H, d, Ja,b = 11.0 Hz,
CH2Ph), 4.62 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.59 (1H,
d, Ja,b = 11.5 Hz, CH2Ph), 4.51 (1H, d, Ja,b = 12.0 Hz,
CH2Ph), 4.50 (1H, d, Ja,b = 11.0 Hz, CH2Ph), 4.35
(1H, dd, J6a,5 = 2 Hz, J6a,6b = 11.5 Hz, H6a), 4.27 (1H,
dd, J6b,5 = 5.0 Hz, J6b,6a = 12.0 Hz, H6b), 3.92 (1H, d,
J2,3 = 7.0 Hz, H2), 3.8–3.72 (4H, m, H4, H5, H8a0,
8b0), 3.70–3.65 (2H, m, H3, H70), 3.59 (3H, s, OCH3),
3.51 (3H, s, OCH3), 3.49 (1H, m, H50), 3.47 (1H, s,
OCH3), 3.37 (1H, s, OCH3), 3.17 (1H, dd,
0
0
0
0
0
0
ArH), 6.05 (1H, dd, J1 ,2a = 11.0 Hz, J1 ,2b = 17.5 Hz,
H10), 5.64 (1H, dd, J2b ,2a = 1.5 Hz, J2b ,1 = 17.5 Hz,
0
0
0
0
H2b0), 3.39 (1H, dd, J2a ,2b = 1.5 Hz, J2a ,1 = 11.0 Hz,
H2a0), 4.90 (1H, d, Ja,b = 11.0 Hz, CH2Ph), 4.86–4.83
(3H, m, CH2Ph · 3), 4.64 (1H, d, Ja,b = 10.5 Hz,
CH2Ph), 4.63 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.61
(1H, d, Ja,b = 11.0 Hz, CH2Ph), 4.56 (1H, d,
Ja,b = 12.0 Hz, CH2Ph), 4.48 (1H, d, Ja,b = 12.0 Hz,
CH2Ph), 4.42 (1H, d, Ja,b = 12.0 Hz, CH2Ph), 4.09
(1H, dd, J3,4 = 9.0 Hz, J3,2 = 9.5 Hz, H3), 3.79–3.7
(3H, m, H5, H6a,b), 3.65 (1H, dd, J4,3 = 9.0 Hz,
J4,5 = 9.5 Hz, H4), 3.39 (1H, d, J2,3 = 9.5 Hz, H2); 13C
NMR (CD2Cl2, 125 MHz): d 139.4, 139, 138.9, 138.8,
136, 128.6, 128.4, 128.2, 128, 127.9, 127.8, 127.7,
119.1, 100.3, 85.0, 83.3, 78.9, 76.1, 75.7, 75.2, 73.7,
72.4, 69.4, 63.9; FABMS: m/z calcd for C43H44O6
[M+H]+: 656.3138.
0
0
0
0
J4 ,3 = 4.0 Hz, J4 ,5 = 10.0 Hz, H40), 3.08 (1H, dd,
0
0
0
0
J6 ,7 = 9.0 Hz, J6 ,5 = 10.0 Hz, H60); 13C NMR
(CD2Cl2, 125 MHz): d 155.3, 153.4, 138.3, 138.2,
138.1, 137.7, 128.6, 128.5, 128.1, 128, 127.9, 103.9,
97.5, 84.7, 83.6, 81.8, 79.6, 78.8, 78.5, 76.9, 74.6, 74.5,
73.7, 68.7, 68.6, 66.5, 62.1, 61.1, 60.8, 59.2, 55.4;
FABMS: m/z calcd for C47H56O13Na [M+Na]+:
851.3619. Found: 851.3634.
0
0
0
0
3.19. n-Hexyl 4,5,6,8-tetra-O-benzyl-1,2-dideoxy-a-D-
gluco-oct-3-ulo-1-enopyranoside (19)
Acknowledgments
A stirred solution of 14 (52 mg, 0.075 mmol) in dry 1-
nitropropane (2 mL) was heated at 125 ꢁC for 4 h. The
solvent was then removed under reduced pressure yield-
ing a residue that was purified by silica gel chromatogra-
phy (1:10, EtOAc/hexanes) to give 19 (9.7 mg, 20%) as a
colorless syrup; Rf 0.2 (1:10, EtOAc/hexanes); [a]D +41
The authors thank the financial support from the
National Science Council of Taiwan (NSC93-2113-M-
001-003 and NSC93-2113-M-001-034) and Academia
Sinica, Taiwan.
1
(c 1.4, CHCl3); H NMR (CD2Cl2, 400 MHz): d 7.41–
0
0
7.27 (20H, m, ArH), 6.01 (1H, dd, J1 ,2a = 11.2 Hz,
References
J1 ,2b = 17.6 Hz, H10), 5.60 (1H, dd, J2b ,2a = 2 Hz,
0
0
0
0
J2b ,1 = 17.6 Hz, H2b0), 5.40 (1H, m, H2a0), 4.96 (1H,
d, Ja,b = 11.2 Hz, CH2Ph), 4.91 (1H, d, Ja,b = 11.2 Hz,
CH2Ph), 4.9 (1H, d, Ja,b = 11.2 Hz, CH2Ph), 4.85 (1H,
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(1H, d, Ja,b = 11.6 Hz, CH2Ph), 4.62 (1H, d,
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H1a00,b00), 1.65–1.6 (2H, m, H2a00,b00), 1.4–1.32 (6H, m,
0
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