Pre-activation of fully acetylated dodecyl thioglycosides with BSP-Tf2O led to efficient glycosylation at low temperature

Article abstract of DOI:10.1016/j.carres.2008.11.008

Fully acetylated dodecyl thioglycosides were found to be useful as glycosyl donors by activation with 1-benzenesulfinyl piperidine (BSP) and triflic anhydride (Tf₂O) at -78 °C. The glycosyl acceptor was added to the reaction mixture at the same

Full text of DOI:10.1016/j.carres.2008.11.008

Carbohydrate Research 344 (2009) 285–290
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Pre-activation of fully acetylated dodecyl thioglycosides with
BSP–Tf2O led to efficient glycosylation at low temperature
*
Sang-Hyun Son, Chiharu Tano, Tetsuya Furuike, Nobuo Sakairi
Graduate School of Environmental Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 April 2008
Received in revised form 11 November 2008
Accepted 12 November 2008
Available online 21 November 2008
Fully acetylated dodecyl thioglycosides were found to be useful as glycosyl donors by activation with
1-benzenesulfinyl piperidine (BSP) and triflic anhydride (Tf2O) at ꢀ78 °C. The glycosyl acceptor was
added to the reaction mixture at the same temperature to furnish various disaccharide, including the
protected Lewis a (Lea) trisaccharide, in good yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Dodecyl thioglycosides
1-Dodecanethiol
Glycosylation
Oligosaccharides
1. Introduction
at their 2-positions usually afford the corresponding 1,2-trans gly-
cosides through neighboring-group participation. However, appli-
Thioglycosides are among the most widely used synthetic inter-
mediates in carbohydrate chemistry because of their ease of prep-
aration, shelf stability, and compatibility with numerous
protection and deprotection reactions.1 The most remarkable fea-
ture of the thioglycosides is that they can be activated as glycosyl
donors by treatment with various thiophilic reagents.2 Total syn-
theses of various complex oligosaccharides have been successfully
achieved by assembly of the thioglycosyl donors.3 Most of the thio-
glycosyl donors are derived by protective-group manipulations of
fully acetylated thioglycosides, which are readily obtained by Le-
wis acid-catalyzed coupling of the corresponding monosaccharide
acetates and thiols.1a Although phenyl and ethyl thioglycosides are
well known as good glycosyl donors, a major disadvantage is the
stench these thiols generate during preparation. Even in a closed
system or in a fume hood, the stench of the volatile thiols is perva-
sive. In the last few years, therefore, odorless methods for prepar-
ing thioglycosides have received much attention.4 Even earlier, in
1993, Tsuchiya and co-workers reported5 that dodecyl 1-thio-b-
maltoside prepared from 1-dodecanethiol was used as a non-ionic
detergent for biological applications. Stimulated by this work, we
prepared various dodecyl thioglycosides and examined their prop-
erties in glycosylation reactions. We have previously demonstrated
that dodecyl thioglycosides of glucose6 and N-acetylneuraminic
acid7 showed excellent reactivity as glycosyl donors.6b,c It is well
known that thioglycosides having O-benzoyl or O-pivaloyl groups
cation of fully acetylated thioglycosides to glycosylation has been
extremely limited. It was observed that glycosidation of dodecyl
thioglycoside acetate gave a complex mixture of products6a,8 in
which an acetyl group of the donor migrated the acceptor, suggest-
ing that an orthoester intermediate was formed during the
reaction.
In complex oligosaccharide synthesis, glycosyl bromides or tri-
chloroacetimidates with sterically less hindered acetyl groups
sometimes played a crucial role in their synthetic strategy.9 In or-
der to extend the synthetic utility of the acetylated thioglycosyl
donors, we re-investigated their glycosylation using various thio-
philic reagents that have been reported. In our previous studies
in oligosaccharide synthesis,6,7 we focused6b,c on the sulfonium tri-
flate pre-activation procedure for thioglycosides, because it forms
highly reactive intermediates like a-glycosyl triflates in the glyco-
sylation process.10 Although the precise mechanism of this novel
method has not yet been established, the triflate intermediate
undergoes glycosylation via either a transient contact ion-pair
mechanism or an SN2-like replacement.11 In this paper, we de-
scribe our recent finding that a trivial modification of the pre-acti-
vation method is highly effective for formation of 1,2-trans
glycosides.
2. Results and discussion
According to an established procedure for the preparation of
thioglycosides, fully acetylated monosaccharides and 1-dode-
canthiol were treated with BF3ꢁEt2O in 1,2-dichloroethane, giving
* Corresponding author. Tel./fax: +81 11 705 2257.
E-mail address: nsaka@ees.hokudai.ac.jp (N. Sakairi).
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.11.008

286
S.-H. Son et al. / Carbohydrate Research 344 (2009) 285–290
Table 1
the dodecyl thiohexopyranosides 1ꢀ6 in good yields. We next
examined glycosylation using these thioglycosides as the donors.
It was reported that BSP–Tf2O pre-activation of fully acetylated
Results of BSP–Tf2O-mediated glycosylationa
Entry
Donor
Product
Yield (%)
1-thio-a-L-rhamnopyranose underwent glycosylation with a par-
tially protected serine derivative at ꢀ60 °C.10b However, our appli-
OMe
BnO
cation of this procedure to coupling dodecyl 2,3,4-tri-O-acetyl-1-
L
-
BnO
O
O
OBn
thio-a-rhamnoside (1) and a monosaccharide acceptor, methyl
1b
1
87
Me
O
2,3,6-tri-O-benzyl-a-D-glucopyranoside (7), was unsuccessful, giv-
AcO
ing several decomposed products of the donor 1 together with an
almost quantitative recovery of unchanged acceptor 7 (Fig. 1).
TLC monitoring of the reaction suggested that the donor 1 was
sufficiently activated by the promoter at ꢀ60 °C to produce several
decomposed products, and that milder conditions would be neces-
sary for this glycosylation procedure with the acetylated
thioglycosides.
OAc
OAc
8
OMe
BnO
OAc
O
BnO
AcO
AcO
O
2b
2
3
4
5
6
88
89
80
83
84
O
OBn
OAc
Thus, we treated the donor 1 with BSP–Tf2O at lower tempera-
ture of ꢀ78 °C, and glycosylation continued at the same tempera-
9
a
-linked disaccharide 812 in 87% yield as the
OMe
BnO
ture, giving known
AcO
AcO
OAc
O
sole product. The 1H NMR spectral data for 8 were consistent with
those reported.12 Furthermore, the configuration of newly gener-
ated rhamnosyl linkage in the disaccharides was confirmed to be
BnO
O
3
O
OBn
OAc
0
0
a-
L
by measuring the one-bond coupling constant, JC1 ,H1 172.5 Hz.
The excellent results of the glycosylation of 1 prompted us to
10
OAc
O
examine the glycosylation of other thioglycoside acetates,
2, -galacto- 3, -manno- 4, 2-deoxy-2-phthalimido- -gluco- 5,
and -fucopyranoside 6, with the acceptor 7 using BSP–Tf2O and
D-gluco-
AcO
OMe
D
D
D
AcO
BnO
AcO
4b
L
BnO
a sterically hindered base as the promoter system. However, glyco-
sylation of donors 2 and 4 gave the corresponding disaccharides in
low yields. Crich and Smith reported that BSP–Tf2O promoted gly-
cosylation of benzoylated glucosyl, mannosyl, and xylosyl donors
in the presence of sterically hindered base to give orthoesters as
major products, while glycosides were obtained in the absence of
base.10b Therefore, we did not add 2,6-di-tert-butyl-4-methylpyri-
dine (DTBM) in the reactions of 1, 2, and 4. Reaction conditions and
results of our glycosylation are summarized in Table 1. All reac-
tions were completed within 1 h at ꢀ78 °C, giving disaccharides
with 1,2-trans configuration in yields of 80–90%. The 1,2-trans con-
figurations of the disaccharides 8–13 were also confirmed by 1H
and 13C NMR spectroscopy. Although we have not obtained posi-
tive evidence, we hypothesized that the glycosylation proceeded
through the corresponding dioxocarbenium ion intermediates
formed by neighboring-group participation of the 2-O-acetyl
groups in a manner similar to that for other acetylated donors.
O
O
OBn
11
OMe
OAc
O
BnO
BnO
O
AcO
AcO
5
O
OBn
NPhth
12
OMe
BnO
BnO
Me
O
O
O
6
OAc
OBn
OAc
AcO
13
a
Typically, the dodecyl thioglycoside donors (2.0 equiv with respect to the
acceptor) were pre-activated by BSP (1.1 equiv with respect to the donor), Tf2O
(1.4 equiv with respect to the donor), and DTBM (2.0 equiv with respect to the
donor) in CH2Cl2 at ꢀ78 °C, followed by addition of the acceptor at the same
temperature.
b
Reactions were performed without DTBM.
SC12H25
OAc
Me
AcO
O
O
AcO
AcO
SC12H25
Encouraged by these successful results of disaccharide forma-
tion, we turned our attention to the synthesis of the Lewis a (Lea)
OAc
OAc
OAc
1
2
antigen trisaccharide, Fuc-
An established synthetic route to the trisaccharide involves the
introduction of the tetra-O-acetyl-b- -galactopyranosyl residue at
the 3-OH group of a -glucosamine derivative by a Koenigs–Knorr
reaction prior to
-fucosylation at the 4-OH group.13 This strategy
a
-(1?4)-(Gal-b-(1?3))-GlcNAc.9a,e,13
AcO
AcO
D
OAc
O
OAc
O
AcO
AcO
D
SC12H25
AcO
a
OAc
SC12H25
is probably used because of the steric hindrance of the neighboring
substituent and/or mismatching between the glycosyl donor and
the acceptor.14 Since thioglycosyl donors have been seldom used
for this glycosylation, we were interested in glycosylation between
3 and the acceptor 14 as shown in Scheme 1. By a process similar to
the glycosylation described above, 3 was pre-activated with BSP–
Tf2O in dry CH2Cl2 at ꢀ78 °C in the presence of 4 Å molecular sieves
and DTBM, and was subsequently treated with the acceptor 14 at
the same temperature. As we expected, this glycosylation pro-
ceeded smoothly, and the desired disaccharide 15 was obtained
3
4
OBn
OAc
O
SC12H25
OAc
Me
O
O
HO
AcO
AcO
SC12H25
BnO
OAc
AcO
BnO
OMe
NPhth
5
6
7
Figure 1. Glycosyl donor (1–6) and acceptor (7) employed in the BSP–Tf2O-
mediated couplings.

S.-H. Son et al. / Carbohydrate Research 344 (2009) 285–290
287
gel (Silica Gel 60; 70ꢀ230 mesh ASTM, E. Merck, Darmstadt,
Germany).
AcO
AcO
OAc
O
O
Ph
O
O
+
1H and 13C NMR spectra were recorded with a Bruker ASX 300
(300 and 75.1 MHz, respectively) and JEOL ECA 600 (600 and
150 MHz, respectively). Chemical shifts (in ppm) were referenced
to Me4Si (d 0 ppm) in CDCl3. 13C NMR spectra were obtained by
using the same NMR spectrometers, and were calibrated with
CDCl3 (d 77.00 ppm). Splitting patterns are indicated as s, singlet;
d, doublet; t, triplet; q, quartet; m, multiplet; br d, broad doublet
for 1H NMR data. High-resolution mass spectra (HRESI-TOFMS)
were measured on a Bruker micro-TOF focus spectrometer.
HO
SC12H25
PhthN
OMe
OAc
3
14
a
OR2
O
AcO
OAc
O
R1O
O
AcO
PhthN
OAc
OMe
1
: R , R2 = >CHPh
3.2. Preparation of dodecyl thioglycosides
15
b
16 : R1 = H, R2 = Bn
General procedure: To a solution of per-O-acetylated sugar and
1-dodecanethiol (1.1 equiv) in 1,2-dichloroethane (10ꢀ20 mL)
was added BF3ꢁOEt2 (1.2 equiv) at 0 °C. The temperature was raised
to room temperature and stirring was continued. After TLC showed
completion of the reaction, the mixture was diluted with CHCl3,
poured into ice-water, and stirred for 30 min. The organic layer
that separated was successively washed with sat aq NaHCO3 and
brine, dried (MgSO4), filtered, and concentrated. The dodecyl thio-
glycoside produced was purified by silica gel chromatography
(5:1?3:1 hexane–EtOAc, gradient elution).
c
SC12H25
OBn
Me
O
OBn
BnO
17
BnO
OBn
OBn
O
OAc
O
AcO
AcO
OBn
O
O
O
PhthN
OAc
OMe
18
3.2.1. Dodecyl 2,3,4-tri-O-acetyl-1-thio-a-L-rhamnopyranoside
(1)
Scheme 1. Reagents and conditions: (a) BSP, DTBM, Tf2O, CH2Cl2, ꢀ78 °C, 1 h, 84%;
(b) NaBH3CN, HClꢀEt2O, THF, 0 °C, 30 min, 72%; (c) BSP, DTBM, Tf2O, CH2Cl2, ꢀ78 °C,
1 h, 85%.
1,2,3,4-Tetra-O-acetyl-a-L-rhamnopyranose (1.00 g, 3.01 mmol)
was treated according to the general procedure described above to
give 1 (1.25 g, 88% yield) as a colorless syrup: ½a D20
ꢀ95.7 (c 1.00,
ꢂ
CHCl3); 1H NMR (300 MHz, CDCl3): d 5.34 (dd, 1H, J2,3 3.3 Hz, H-
2), 5.23 (dd, 1H, J3,4 10.0 Hz, H-3), 5.16 (d, 1H, J1,2 1.5 Hz, H-1),
5.09 (t, 1H, J4,5 9.8 Hz, H-4), 4.23 (m, 1H, H-5), 2.70ꢀ2.54 (m, 2H,
SCH2), 2.16, 2.05, 1.98 (3s, each 3H, acetyl), 1.65ꢀ1.22 (m, 23H,
SCH2(CH2)10CH3, H-6), 0.88 (t, 3H, J 6.5 Hz, CH2CH3); 13C NMR
(75 MHz, CDCl3): d 170.0, 169.9, 169.8 (C@O), 82.4, 71.6, 71.3,
69.5, 66.9, 31.8, 31.5, 29.5, 29.5, 29.4, 29.3, 29.1, 28.7, 22.6, 20.9,
20.7, 20.6, 17.3, 14.0; Anal. Calcd for C24H42O7S: C, 60.73; H,
8.92; S, 6.76. Found: C, 60.60; H, 8.90; S, 6.66.
in an excellent yield of 84%. The anomeric configuration of 15 was
0
0
confirmed to be b on the basis of its coupling constant (J1 ,2 7.8 Hz,
H-10) for the anomeric proton at 4.76 ppm in the 1H NMR spectrum
13
and the chemical shift in C NMR spectrum at 100.5 ppm (C-10).
For the next step, the
a-fucosylation at the 4-position, the disac-
charide 15 was converted into glycosyl acceptor 16 by reductive
ring opening of the benzylidene acetal. Thus, 15 was treated with
NaBH3CN–HCl in THF at 0 °C, giving the 4-OH derivative 16 in
72% yield. The a-L-fucosylation using the benzylated thioglycoside
donor 17 was also successful with BSP–Tf2O in dry CH2Cl2 at
ꢀ78 °C, giving fully protected Lea trisaccharide 18 in 85% yield.
Both the 1H and 13C NMR spectra, as well as the high-resolution
MS spectrum, supported its structure.
In summary, a simple modification of Crich’s procedure for the
per-activation of thioglycosides was found to result in a dramati-
cally improved ability of fully acetylated thioglycosides to serve
as glycosyl donors. On treatment with BSP–Tf2O at ꢀ78 °C, fully
acetylated dodecyl thioglycosides coupled with glycosyl acceptors
at the same temperature to give various disaccharides and a pre-
cursor of Lea trisaccharide in excellent yields.
3.2.2. Dodecyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
glucopyranoside (2)
1,2,3,4,6-Penta-O-acetyl-b-D-glucopyranose (0.78 g, 2.0 mmol)
was treated according to the general procedure described above
to give 2 (1.00 g, 95% yield) as a colorless solid: ½a D20
ꢀ29.2 (c
ꢂ
0.12, CHCl3); 1H NMR (300 MHz, CDCl3): d 5.24 (t, 1H, J3,4 9.3 Hz,
H-3), 5.10 (t, 1H, J4,5 9.5 Hz, H-4), 5.05 (t, 1H, J2,3 9.4 Hz, H-2),
4.49 (d, 1H, J1,2 10.0 Hz, H-1), 4.26 (dd, 1H, J5,6b 4.9 Hz, H-6b),
4.05 (dd, 1H, J5,6a 2.2 Hz, J6a,6b 12.4 Hz, H-6a), 3.75ꢀ3.65 (m, 1H,
H-5), 2.76ꢀ2.60 (m, 2H, SCH2), 2.10, 2.08, 2.04, 2.03 (4s, each 3H,
acetyl), 1.66ꢀ1.26 (m, 20H, SCH2(CH2)10CH3), 0.88 (t, 3H, J 4.1 Hz,
CH2CH3); 13C NMR (75 MHz, CDCl3): d 171.1, 170.7, 169.9, 169.9
(C@O), 84.2, 76.4, 74.5, 70.5, 68.9, 62.8, 32.4, 30.6, 30.2, 30.1,
30.1, 29.9, 29.7, 29.3, 23.2, 21.2, 21.1, 14.6; Anal. Calcd for
C26H44O9S: C, 58.62; H, 8.33; S, 6.02. Found: C, 58.55; H, 8.46; S,
6.17.
3. Experimental
3.1. General methods
All chemicals purchased were of reagent grade, and were used
without further purification. Dichloromethane (CH2Cl2) and 1,2-
dichloroethane were distilled over calcium hydride (CaH2). Molec-
ular sieves used for glycosylation were 4 Å MS, which were acti-
vated at 200 °C under reduced pressure prior to use. Reactions
were monitored by thin-layer chromatography (TLC) on a pre-
coated plates of Silica Gel 60F254 (layer thickness, 0.25 mm; E.
Merck, Germany), which were visualized under UV (254 nm)
and/or by spraying with p-methoxybenzaldehydeꢀH2SO4ꢀMeOH
(1:2:17, v/v). Column chromatography was performed on silica
3.2.3. Dodecyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
galactopyranoside (3)
1,2,3,4,6-Penta-O-acetyl-b-
D-galactopyranose
(0.78 g,
2.0 mmol) was treated according to the general procedure de-
scribed above to give 3 (1.05 g, 99% yield) as a colorless solid:
½
a 2D0
ꢂ
ꢀ16.0 (c 0.30, CHCl3); 1H NMR (300 MHz, CDCl3): d 5.43 (d,
1H, J4,5 3.3 Hz, H-4), 5.27 (t, 1H, J2,3 10.0 Hz, H-2), 5.04 (dd, 1H,
J3,4 10.0 Hz, H-3), 4.47 (d, 1H, J1,2 9.9 Hz, H-1), 4.25ꢀ4.05 (m, 2H,
H-6a, 6b), 3.94ꢀ3.91 (m, 1H, H-5), 2.73ꢀ2.65 (m, 2H, SCH2), 2.17,

288
S.-H. Son et al. / Carbohydrate Research 344 (2009) 285–290
2.16, 2.07, 2.05 (4s, each 3H, acetyl), 1.66ꢀ1.26 (m, 20H,
SCH2(CH2)10CH3), 0.88 (t, 3H,
4.1 Hz, CH2CH3); 13C NMR
(75 MHz, CDCl3): d 170.4, 170.2, 170.1, 169.5 (C@O), 84.2, 74.3,
71.9, 67.3, 61.4, 31.9, 30.9, 30.2, 29.7, 29.6, 29.5, 29.3, 29.2, 28.8,
22.6, 20.8, 20.6, 20.6, 14.1; Anal. Calcd for C26H44O9S: C, 58.62; H,
8.33; S, 6.02. Found: C, 58.65; H, 8.35; S, 6.05.
6.4 Hz, H-6), 0.88 (t, 3H, J 6.5 Hz, CH2CH3); 13C NMR (75 MHz,
CDCl3): d 170.4, 169.8, 169.4 (C@O), 83.6, 73.1, 72.3, 70.4, 67.3,
31.9, 29.8, 29.6, 29.6, 29.5, 29.3, 29.2, 28.8, 22.7, 20.8, 20.7, 20.6,
16.4, 14.1; Anal. Calcd for C24H42O7S: C, 60.73; H, 8.92; S, 6.76.
Found: C, 60.70; H, 8.98; S, 6.86.
J
3.3. Glycosylation between the donors 1–6 and the acceptor 7
3.2.4. Dodecyl 2,3,4,6-tetra-O-acetyl-1-thio-a-D-
mannopyranoside (4)
General procedure: A suspension of the dodecyl thioglycosides
1–6 (0.6 mmol, 2.0 equiv), BSP (138.1 mg, 0.66 mmol, 1.1 equiv to
thioglycoside), and 4 Å MS (700 mg) was stirred in dry CH2Cl2
(6 mL) at room temperature for 30 min under a nitrogen atmo-
sphere. The reaction mixture was cooled to ꢀ78 °C, followed by
1,2,3,4,6-Penta-O-acetyl-a-D-mannopyranose (2.0 g, 5.0 mmol)
was treated according to the general procedure described above
to give 4 (2.3 g, 86% yield) as a colorless solid: ½a D20
ꢂ
+76.8 (c 0.37,
CHCl3); 1H NMR (300 MHz, acetone): d 5.38 (br d, 1H, H-1), 5.31
(dd, 1H, J2,3 3.2 Hz, H-2), 5.23 (t, 1H, J4,5 9.5 Hz, H-4), 5.19 (dd,
1H, J3,4 9.9 Hz, H-3), 4.41ꢀ4.33 (m, 1H, H-5), 4.24 (dd, 1H, J5,6a
5.8 Hz, J6a,6b 12.1 Hz, H-6a), 4.10 (dd, 1H, J5,6b 2.4 Hz, H-6b),
2.79ꢀ2.60 (m, 2H, SCH2), 2.11, 2.05, 2.03, 1.95 (4s, each 3H, acetyl),
1.66ꢀ1.26 (m, 20H, SCH2(CH2)10CH3), 0.88 (t, 3H, J 4.1 Hz, CH2CH3);
13C NMR (75 MHz, acetone): d 170.1, 170.0, 169.8, 169.7 (C@O),
82.6, 82.4, 76.4, 71.1, 69.9, 69.5, 66.5, 62.8, 32.1, 31.5, 31.1, 22.8,
20.2, 20.1, 20.0, 13.8; Anal. Calcd for C26H44O9S: C, 58.62; H,
8.33; S, 6.02. Found: C, 58.63; H, 8.38; S, 6.06.
addition of Tf2O (137 lL, 0.82 mmol, 1.4 equiv to thioglycoside)
and was stirred at the same temperature for 15 min. A solution
of methyl 2,3,6-tri-O-benzyl- -glucopyranoside (7, 139.0 mg,
a-D
0.3 mmol, 1.0 equiv) in dry CH2Cl2 (2 mL) was slowly added to
the resulting mixture for 10 min. The reaction mixture was stirred
at this temperature for 1 h, quenched by addition of Et3N, diluted
with CHCl3, and filtered through a pad of Celite. The filtrate was
successively washed with satd aq NaHCO3 and brine, dried
(MgSO4), and concentrated. The residue was purified by column
chromatography.
3.2.5. Dodecyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-
thio-b-
D-glucopyranoside (5)
3.3.1. Methyl 2,3,4-tri-O-acetyl-
a-L-rhamnopyranosyl-(1?4)-
1,3,4,6-Tetra-O-acetyl-2-phthalimido-2-deoxy-b-
D-glucopyra-
2,3,6-tri-O-benzyl- -glucopyranoside (8)
a-D
nose (2.58 g, 5.42 mmol) was treated according to the general pro-
Dodecyl thiorhamnoside 1 (284.8 mg, 0.6 mmol) was con-
densed with the glycosyl acceptor 7 (139 mg, 0.3 mmol) in dry
CH2Cl2 (8 mL) in the presence of BSP (138.1 mg, 0.66 mmol), Tf2O
cedure described above to give 5 (2.73 g, 81% yield) as a colorless
solid: ½a 2D0
ꢂ
+22.7 (c 2.63, CHCl3); 1H NMR (300 MHz, CDCl3): d
7.89ꢀ7.74 (m, 5H, CHarom), 5.83 (t, 1H, J3,4 9.2 Hz, H-3), 5.46 (d,
1H, J1,2 10.6 Hz, H-1), 5.18 (t, 1H, J4,5 9.4 Hz, H-4), 4.39 (t, 1H, J2,3
10.4 Hz, H-2), 4.31 (dd, 1H, J5,6a 4.8 Hz, J6a,6b 8.2 Hz, H-6a), 4.17
(dd, 1H, J5,6b 2.1 Hz, H-6b), 3.93ꢀ3.85 (m, 1H, H-5), 2.67ꢀ2.62
(m, 2H, SCH2), 2.10, 2.04, 1.87 (3s, each 3H, acetyl), 1.60ꢀ1.24
(m, 20H, SCH2(CH2)10CH3), 0.88 (t, 3H, J 6.2 Hz, CH2CH3); 13C
NMR (75 MHz, CDCl3): d 170.7, 170.1, 169.5, 167.8, 167.2 (C@O),
134.4, 134.3, 131.6, 131.2, 123.7, 81.4, 77.2, 77.0, 76.6, 75.9, 71.5,
68.8, 62.3, 53.7, 31.9, 30.3, 29.6, 29.5, 29.3, 29.1, 28.7, 22.7, 20.8,
20.7, 20.5, 14.1; Anal. Calcd for C32H45NO9S: C, 62.01; H, 7.32; N,
2.26; S, 5.17. Found: C, 61.84; H, 7.20; N, 2.27; S, 5.26.
(137 lL, 0.82 mmol), and 4 Å MS (700 mg) following the general
procedure described above. Column chromatography (10:1?6:1
toluene–EtOAc, gradient elution) provided the disaccharide 8
(188 mg, 87% yield). Spectral data for 8 were consistent with those
reported previously.12
3.3.2. Methyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl-(1?4)-
2,3,6-tri-O-benzyl- -glucopyranoside (9)
a-D
Dodecyl thioglucoside 2 (320 mg, 0.6 mmol) was condensed
with the glycosyl acceptor 7 (139 mg, 0.3 mmol) in dry CH2Cl2
(8 mL) in the presence of BSP (138.1 mg, 0.66 mmol), Tf2O
(137 lL, 0.82 mmol), and 4 Å MS (700 mg) following the general
3.2.6. Dodecyl 2,3,4-tri-O-acetyl-1-thio-b-
L
-fucopyranoside (6)
procedure described above. Column chromatography (7:1?2:1
toluene–EtOAc, gradient elution) provided the disaccharide 9
(210 mg, 88% yield). Spectral data for 9 were consistent with those
reported previously.12,16
L-Fucose (2.0 g, 12.2 mmol) was dissolved in Ac2O (20 mL) and
pyridine (20 mL) and was stirred for 12 h. The reaction was
quenched by addition of ice-water, and the mixture was stirred
overnight and extracted with EtOAc. The organic layer was succes-
sively washed with satd aq NaHCO3 and brine, dried (MgSO4), fil-
tered, and concentrated. Column chromatography (2:1
3.3.3. Methyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl-
(1?4)-2,3,6-tri-O-benzyl- -glucopyranoside (10)
a
-D
hexaneꢀEtOAc) yielded 4.0 g (quant) of 1,2,3,4-tetra-O-acetyl-
cose as a 7:3 mixture of and b anomers, [(d 6.36 (d, J1,2 2.19 Hz,
H-1 ), 5.68 (d, J1,2 8.29 Hz, H-1b)].
L
-fu-
Dodecyl thiogalactoside 3 (320 mg, 0.6 mmol) was condensed
with the glycosyl acceptor 7 (139 mg, 0.3 mmol) in dry CH2Cl2
(8 mL) in the presence of BSP (138.1 mg, 0.66 mmol), Tf2O
a
a
The resulting acetate (4.0 g, 12.0 mmol) and 1-dodecanethiol
(1.0 mL, 3.96 mmol) were stirred in 1,2-dichloroethane (20 mL)
at 0 °C. BF3ꢁOEt2 (0.5 mL, 4.32 mmol) was added, and the mixture
was stirred for 4 h at this temperature. The reaction mixture was
quenched by addition of ice-water and was stirred for 30 min.
The organic layer was successively washed with satd aq NaHCO3
and brine, dried (MgSO4), filtered, and concentrated. The residue
was purified by column chromatography (3:1 hexaneꢀEtOAc) to
(137 lL, 0.82 mmol), DTBM (246.8 mg, 1.2 mmol), and 4 Å MS
(700 mg) following the general procedure described above. Col-
umn chromatography (7:1?2:1 toluene–EtOAc, gradient elu-
tion) provided the disaccharide 10 (213 mg, 89% yield).
Spectral data for 10 were consistent with those reported
previously.3,15
3.3.4. Methyl 2,3,4,6-tetra-O-acetyl-a-D-mannopyranosyl-
afford unreacted
a
-acetate (2.72 g, 68% recovery) and 6 (1.43 g,
(1?4)-2,3,6-tri-O-benzyl- -glucopyranoside (11)
a-D
84% yield, based on the consumed b-acetate) as a colorless syrup:
Dodecyl thiomannoside 4 (320 mg, 0.6 mmol) was condensed
with the glycosyl acceptor 7 (139 mg, 0.3 mmol) in dry CH2Cl2
(8 mL) in the presence of BSP (138.1 mg, 0.66 mmol), Tf2O
(137 lL, 0.82 mmol), and 4 Å MS (700 mg) following the general
procedure described above. Column chromatography (10:1?4:1
½
a 2D0
ꢂ
ꢀ16.5 (c 0.26, CHCl3); 1H NMR (300 MHz, CDCl3): d 5.27 (d,
1H, J4,5 3.2 Hz, H-4), 5.21 (t, 1H, J2,3 9.9 Hz, H-2), 5.04 (dd, 1H, J3,4
10.0 Hz, H-3), 4.44 (d, 1H, J1,2 = 9.9 Hz, H-1), 3.81 (dd, 1H, J5,6
12.7 Hz, H-5), 2.72ꢀ2.64 (m, 2H, SCH2), 2.18, 2.06, 1.99 (3s, each
3H, acetyl), 1.61ꢀ1.25 (m, 20H, SCH2(CH2)10CH3), 1.22 (d, 3H, J
toluene–EtOAc, gradient elution) provided the disaccharide 11

S.-H. Son et al. / Carbohydrate Research 344 (2009) 285–290
289
(189 mg, 80% yield). Spectral data for 11 were consistent with
at ꢀ78 °C under a nitrogen atmosphere was added Tf2O (137
lL,
those reported previously.12
0.82 mmol). After 15 min, a solution of the glycosyl acceptor 14
(370.0 mg, 0.9 mmol) in dry CH2Cl2 was added. The reaction mix-
ture was stirred at the same temperature for 1 h, and the reaction
was quenched by addition of Et3N. The mixture was diluted with
CHCl3 and filtered through a pad of Celite. The filtrate was succes-
sively washed with satd aq NaHCO3 and brine, dried (MgSO4), and
concentrated. The residue was purified by column chromatography
(5:1?2:1 toluene–EtOAc, gradient elution) to provide 15 (372 mg,
3.3.5. Methyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-b-D-
glucopyranosyl-(1?4)-2,3,6-tri-O-benzyl-a-D-glucopyranoside
(12)
The N-phthaloyl glucosamine derivative 5 (372 mg, 0.6 mmol)
was condensed with the glycosyl acceptor 7 (418 mg, 0.9 mmol)
in dry CH2Cl2 (8 mL) in the presence of BSP (138.1 mg, 0.66 mmol),
Tf2O (137
l
L, 0.82 mmol), DTBM (246.8 mg, 1.2 mmol), and 4 Å MS
84% yield) as a colorless syrup: ½a D21
ꢂ
+62.4 (c 1.00, CHCl3); 1H NMR
(700 mg) following the general procedure described above. Col-
umn chromatography (10:1?2:1 toluene–EtOAc, gradient elution)
provided the disaccharide 12 (220 mg, 83% yield) as a colorless syr-
(600 MHz, CDCl3): d 7.97ꢀ7.21 (m, 9H, CHarom), 5.59 (s, 1H, PhCH),
5.45 (t, 1H, J3,4 9.2 Hz, H-3), 5.21 (d, 1H, J4 ,5 3.4 Hz, H-40), 4.96 (t,
0 0
1H, J2 ,3 9.4 Hz, H-20), 4.81 (dd, 1H, J3 ,4 10.4 Hz, H-30), 4.77 (d,
0
0
0
0
up: ½a 2D2
ꢂ
+18.3 (c 1.00, CHCl3); 1H NMR (600 MHz, CDCl3): d
1H, J1,2 3.3 Hz, H-1), 4.76 (d, 1H, J1 ,2 7.8 Hz, H-10), 4.47 (dd, 1H,
J2,3 10.7 Hz, H-2), 4.30 (dd, 1H, J5,6b 4.4 Hz, H-6b), 4.07ꢀ3.97 (m,
2H, H-6a, 60b), 3.88ꢀ3.75 (m, 3H, H-4, 5, 60a), 3.54ꢀ3.47 (m, 1H,
H-50), 3.32 (s, 3H, OMe), 2.05, 1.94, 1.85, 1.74 (4s, each, 3H, acetyl);
13C NMR (75 MHz, CDCl3): d 170.8, 170.6, 170.5, 169.7 (C@O),
168.9, 168.3, 137.6, 134.8, 134.5, 132.8, 132.4, 129.8, 129.5,
128.9, 128.7, 126.6, 123.9, 102.2, 100.5, 99.6, 82.2, 72.9, 71.9,
71.8, 71.6, 71.3, 69.5, 69.4, 67.2, 62.9, 61.3, 56.0, 55.5, 21.1, 21.0,
20.9; HRESIMS: m/z [M+Na]+ calcd for C36H39NO16Na: 764.2161;
found: 764.2178.
0
0
7.83ꢀ7.21 (m, 19H, CHarom), 5.69 (t, 1H, J3 ,4 9.8 Hz, H-30), 5.63
0
0
(d, 1H, J1 ,2 8.8 Hz, H-10), 5.11 (t, 1H, J4 ,5 9.4 Hz, H-40), 4.99 (d,
1H, J 11.5 Hz, PhCH2), 4.91 (d, 1H, J 11.6 Hz, PhCH2), 4.68 (d, 1H, J
12.7 Hz, PhCH2), 4.55 (d, 1H, J 12.1 Hz, PhCH2), 4.50 (d, 1H, J1,2
3.8 Hz, H-1), 4.35 (d, 1H, J 11.5 Hz, PhCH2), 4.33 (d, 1H, J 12.0 Hz,
0
0
0
0
PhCH2), 4.25 (dd, 1H, J2 ,3 10.4 Hz, H-20), 4.07 (dd, 1H, J5 ,6 a
0
0
0
0
3.8 Hz, J6 a,6 b 12.4 Hz, H-60a), 3.98 (t, 1H, J4,5 9.0 Hz, H-4), 3.88 (t,
0
0
1H, J3,4 9.3 Hz, H-3), 3.80 (dd, 1H, J5 ,6 b 1.8 Hz, H-60b), 3.58ꢀ3.53
(m, 1H, H-50), 3.45 (dd, 1H, J2,3 9.6 Hz, H-2), 3.44ꢀ3.41 (m, 2H, H-
6a, 6b), 3.37ꢀ3.32 (m, 1H, H-5), 3.26 (s, 3H, OMe), 1.98, 1.97,
1.82 (3s, each, 3H, acetyl); 13C NMR (75 MHz, CDCl3): d 170.1,
170.6, 169.8 (C@O), 131.8, 129.4, 128.7, 128.7, 128.5, 128.2,
127.8, 127.7, 127.5, 127.3, 125.7, 124.0, 98.4, 97.7, 80.6, 79.8,
75.9, 75.1, 73.8, 73.2, 72.0, 71.2, 69.7, 68.8, 68.6, 61.9, 55.8, 55.7,
21.1, 21.0, 20.8; HRESIMS: m/z [M+Na]+ calcd for C48H51NO15Na:
904.3151; found: 904.3143.
0
0
3.4.2. Methyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl-
(1?3)-6-O-benzyl-2-deoxy-2-phthalimido-a-D-glucopyranoside
(16)
Sodium cyanoborohyride (211 mg, 3.36 mmol) was added to a
stirring solution of the disaccharide 15 (208 mg, 0.18 mmol) in an-
hyd. THF (5 mL) containing 4 Å MS (500 mg). A solution of HCl in
Et2O (2 M) was added dropwise until the evolution of gas ceased.
After stirring for an additional 30 min, the mixture was filtered
through Celite and washed successively with satd aq NaHCO3
and brine, dried (MgSO4), filtered, and concentrated. The crude
mixture was purified by column chromatography (5:1?2:1 tolu-
eneꢀEtOAc, gradient elution) to give acceptor 16 as a colorless syr-
3.3.6. Methyl 2,3,4-tri-O-acetyl-b-
L-fucopyranosyl-(1?4)-2,3,6-
tri-O-benzyl- -glucopyranoside (13)
a
-D
Dodecyl thiofucoside 6 (284.8 mg, 0.6 mmol) was condensed
with the glycosyl acceptor 7 (139 mg, 0.3 mmol) in dry CH2Cl2
(8 mL) in the presence of BSP (138.1 mg, 0.66 mmol), Tf2O
(137
l
L, 0.82 mmol), DTBM (246.8 mg, 1.2 mmol), and 4 Å MS
up (149 mg, 72% yield): ½a D22
ꢂ
+93.6 (c 1.00, CHCl3); 1H NMR
0
0
(700 mg) following the general procedure described above. Col-
umn chromatography (10:1?5:1 toluene–EtOAc, gradient elution)
provided the disaccharide 13 (183 mg, 84% yield) as a colorless syr-
(600 MHz, CDCl3): d 7.95ꢀ7.25 (m, 9H, CHarom), 5.33 (d, 1H, J4 ,5
2.8 Hz, H-40), 5.21 (t, 1H, J3,4 9.9 Hz, H-3), 5.12 (t, 1H, J2 ,3 8.8 Hz,
0 0
H-20), 4.92 (dd, 1H, J3 ,4 10.4 Hz, H-30), 4.79 (d, 1H, J1,2 3.3 Hz, H-
0
0
up: ½a 2D2
ꢂ
+22.1 (c 1.00, CHCl3); 1H NMR (600 MHz, CDCl3): d
1), 4.72 (d, 1H, J1 ,2 8.2 Hz, H-10), 4.65 (d, 1H, J 12.6 Hz, PhCH2),
4.63 (d, 1H, J 12.1 Hz, PhCH2), 4.40 (dd, 1H, J2,3 10.7 Hz, H-2),
4.23 (s, 1H, OH), 4.18ꢀ4.11 (m, 2H, H-60a, 60b), 4.06ꢀ4.02 (m, 1H,
H-50), 3.89ꢀ3.82 (m, 2H, H-5, 6a), 3.76 (dd, 1H, J5,6b 4.9 Hz, H-
6b), 3.68 (t, 1H, J4,5 9.4 Hz, H-4), 3.32 (s, 3H, OMe), 2.13, 2.04,
1.88, 1.07 (4s, each, 3H, acetyl); 13C NMR (75 MHz, CDCl3): d
171.1, 170.7, 170.5, 169.2, 168.9, 168.8 (C@O), 138.9, 135.1,
134.8, 134.7, 132.9, 131.4, 128.9, 128.1, 124.4, 123.9, 100.7, 99.1,
79.8, 75.5, 74.0, 71.8, 71.7, 71.5, 70.1, 69.7, 69.2, 67.6, 62.1, 55.8,
55.3, 21.2, 21.1, 19.6; HRESIMS: m/z [M+Na]+ calcd for C36H41NO16-
Na: 743. 2425; found: 743.2403.
0
0
7.43ꢀ7.21 (m, 15H, CHarom), 5.16 (d, 1H, J4 ,5 3.7 Hz, H-40), 5.15
0
0
(t, 1H, J2 ,3 9.7 Hz, H-20), 5.01 (d, 1H, J1 ,2 8.2 Hz, H-10), 4.99 (d,
0
0
0
0
1H, J 9.9 Hz, PhCH2), 4.93 (dd, 1H, J3 ,4 10.4 Hz, H-30), 4.76 (d, 1H,
J 12.1 Hz, PhCH2), 4.69 (d, 1H, J 9.9 Hz, PhCH2), 4.64 (d, 1H, J
11.6 Hz, PhCH2), 4.62 (d, 1H, J1,2 3.3 Hz, H-1), 4.61 (d, 1H, J
11.6 Hz, PhCH2), 4.53 (d, 1H, J 12.1 Hz, PhCH2), 3.90 (t, 1H, J3,4
8.8 Hz, H-3), 3.86 (t, 1H, J4,5 9.4 Hz, H-4), 3.80 (dd, 1H, J5,6b
1.6 Hz, H-6b), 3.74ꢀ3.69 (m, 1H, H-5), 3.63 (dd, 1H, J5,6a 4.4 Hz,
0
0
J6a,6b 10.7 Hz H-6a), 3.57 (dd, 1H, J5 ,6 12.9 Hz, H-50), 3.53 (dd, 1H,
J2,3 9.3 Hz, H-2), 3.38 (s, 3H, OMe), 2.16, 2.06, 1.99 (3 s, each, 3H,
acetyl), 1.03 (d, 3H, J 6.6 Hz, H-60); 13C NMR (75 MHz, CDCl3): d
171.1, 170.6, 170.0 (C@O), 138.9, 138.6, 138.3, 129.5, 129.2,
129.0, 128.8, 128.7, 128.6, 128.6, 128.5, 127.9, 127.8, 100.7, 98.1,
82.4, 80.5, 77.2, 76.5, 74.3, 73.9, 73.7, 71.8, 70.8, 69.8, 69.7, 69.4,
69.1, 21.4, 21.2, 16.5; HRESIMS: m/z [M+Na]+ calcd for
C40H48O13Na: 759.2987; found: 759.2963.
0
0
3.4.3. Dodecyl 2,3,4-tri-O-benzyl-1-thio-b-
L-fucopyranoside (17)
Dodecyl 2,3,4-tri-O-acetyl-1-thio-b- -fucopyranoside 6 (1.4 g,
L
2.9 mmol) was dissolved in dry MeOH (15 mL), and methanolic
NaOMe (25%, w/v, 0.2 mL) was added. The solution was stirred at
room temperature for 2 h and neutralized with Amberlite IR 50
(H+). Subsequent removal of the resin by filtration and evaporation
of the solvent gave a white solid. The dry product was further trea-
ted with benzyl bromide (1.6 mL, 13.1 mmol) and NaH (60% in
mineral oil, 13.1 mmol) in DMF at 0 °C. The reaction mixture was
stirred at room temperature for 3 h, and the reaction was quenched
with MeOH and aq NH4OH (25%, w/v), which was then coevaporat-
ed with toluene (20 mL ꢃ 3). The crude product was diluted with
EtOAc (100 mL), and the organic layer was washed with satd aq
NaHCO3 and brine, dried (MgSO4), and concentrated. The residual
3.4. Synthesis of fully protected Lea trisaccharide 18
3.4.1. Methyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl)-
(1?3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-a-D-
glucopyranoside (15)
To a stirred suspension containing the thiogalactosyl donor 3
(320 mg, 0.6 mmol), BSP (138.1 mg, 0.66 mmol), DTBM
(216.8 mg, 1.2 mmol), and 4 Å MS (700 mg) in dry CH2Cl2 (6 mL)

290
S.-H. Son et al. / Carbohydrate Research 344 (2009) 285–290
syrup was purified by column chromatography (10:1?3:1 hex-
aneꢀEtOAc, gradient elution) to give the benzylated thiofucoside
Acknowledgment
17 as a colorless solid (1.9 g, 93% yield): ½a D22
ꢂ
+9.3 (c 1.00, CHCl3);
We would like to thank Ms. A. Meada (Center for Instrumental
Analysis, Hokkaido University) for elemental analyses.
1H NMR (300 MHz, CDCl3): d 7.58ꢀ7.11 (m, 15H, CHarom), 5.03 (d,
1H, J 10.4 Hz, PhCH2), 4.90 (d, 1H, J 10.1 Hz, PhCH2), 4.79 (d, 1H, J
10.1 Hz, PhCH2), 4.75 (s, 2H, PhCH2), 4.69 (d, 1H, J 11.8 Hz, PhCH2),
4.36 (d, 1H, J1,2 9.6 Hz, H-1), 3.81 (t, 1H, J2,3 9.4 Hz, H-2), 3.60 (d,
1H, J4,5 2.4 Hz, H-4), 3.55 (dd, 1H, J3,4 9.2 Hz, H-3), 3.46 (dd, 1H,
J5,6 12.9 Hz, H-5), 2.81ꢀ2.59 (m, 2H, SCH2), 1.66ꢀ1.18 (m, 23H,
SCH2(CH2)10CH3, H-6), 0.88 (t, 3H, J 6.5 Hz, CH2CH3); 13C NMR
(75 MHz, CDCl3): d 139.2, 139.0, 138.9, 129.0, 129.0, 128.9, 128.7,
128.6, 128.3, 128.2, 128.1, 128.0, 85.7, 85.0, 78.9, 76.9, 76.3, 75.0,
73.4, 32.5, 31.2, 30.4, 30.3, 30.2, 30.1, 29.9, 29.8, 29.5, 23.2, 17.8,
14.7; HRESIMS: m/z [M+Na]+ calcd for C39H54O4SNa: 641.3635;
found: 641.3607.
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2930–2931; (b) Mezzato, S.; Schaffrath, M.; Unverzagt, C. Angew. Chem., Int. Ed.
2005, 44, 1650–1654; (c) Kashiwagi, I. T.; Totani, K.; Ito, Y. Tetrahedron Lett.
2005, 46, 4197–4200; (d) Amin, M. N.; Ishiwata, A.; Ito, Y. Tetrahedron 2007, 63,
8181–8198; (e) Liao, L.; Auzanneau, F. I. J. Org. Chem. 2005, 70, 6265–6273. and
references cited therein.
3.4.4. Methyl 2,3,4,6-tetra-O-acetyl-b-
(1?3)-[2,3,4-tri-O-benzyl- -fucopyranosyl)-(1?4)-]-6-O-
benzyl-2-deoxy-2-phthalimido- -glucopyranoside (18)
To stirred suspension of 17 (241 mg, 0.39 mmol), BSP
D-galactopyranosyl-
a
-L
a
-D
a
(90.0 mg, 0.43 mmol), DTBM (177 mg, 0.86 mmol), and 4 Å MS
(500 mg) in dry CH2Cl2 (5.0 mL) at ꢀ78 °C under a nitrogen atmo-
sphere was added Tf2O (88 lL, 0.52 mmol). The reaction mixture
was stirred for 15 min, after which time disappearance of 17 was
detected by TLC. solution of the acceptor 16 (191 mg,
A
0.26 mmol) in dry CH2Cl2 (2.0 mL) was then added dropwise.
The reaction mixture was stirred at the same temperature for
1 h, and the reaction was quenched by addition of Et3N. The mix-
ture was then diluted with CHCl3 and filtered through a pad of
Celite. The filtrate was successively washed with satd aq NaHCO3
and brine, dried (MgSO4), and concentrated. The residue was
purified by column chromatography (5:1?1:1 hexane–EtOAc,
gradient elution) to provide the fully protected trisaccharide 18
(252 mg, 85% yield) as a colorless syrup: ½a D21
ꢂ
+28.8 (c 1.00,
CHCl3); 1H NMR (600 MHz, CDCl3): d 7.91ꢀ7.19 (m, 24H, CHarom),
5.33 (dd, 1H, J3,4 10.4 Hz, H-3), 5.24 (d, 1H, J1 ,2 3.3 Hz, H-100),
00 00
5.12 (d, 1H, J4 ,5 3.8 Hz, H-40), 4.99 (d, 1H, J 12.1 Hz, PhCH2),
0
0
4.98 (dd, 1H, J2 ,3 10.4 Hz, H-20), 4.89 (d, 1H, J 11.6 Hz, PhCH2),
4.84 (s, 2H, PhCH2), 4.83 (d, 1H, J 11.5 Hz, PhCH2), 4.87ꢀ4.81
(m, 1H, H-500), 4.66 (d, 1H, J 11.5 Hz, PhCH2), 4.65 (d, 1H, J1,2
0
0
3.3 Hz, H-1), 4.53 (dd, 1H, J3 ,4 10.4 Hz, H-30), 4.48 (dd, 1H, J2,3
0
0
10.4 Hz, H-2), 4.44 (d, 1H, J1 ,2 8.1 Hz, H-10), 4.42 (d, 1H, J
0
0
00 00
12.1 Hz, PhCH2), 4.36 (d, 1H, J 12.1 Hz, PhCH2), 4.25 (t, 1H, J2 ,3
10. (a) Crich, D.; Cai, W. J. Org. Chem. 1999, 64, 4926–4930; (b) Crich, D.; Smith, M.
J. Am. Chem. Soc. 2001, 123, 9015–9020.
10.1 Hz, H-200), 4.16 (dd, 1H, J5 ,6 a 3.8 Hz, J6 a,6 b 9.9 Hz, H-60a),
4.15ꢀ3.91 (m, 5H, H-4, 6a, 6b, 60b, 300), 3.83ꢀ3.76 (m, 2H, H-50,
400), 3.61ꢀ3.54 (m, 1H, H-5), 3.21 (s, 3H, OMe), 2.01, 1.83, 1.81,
1.73 (4s, each, 3H, acetyl), 1.29 (d, 3H, J 6.6 Hz, H-600); 13C NMR
0
0
0
0
11. Crich, D.; Chandrasekera, N. S. Angew. Chem., Int. Ed. 2004, 43, 5386–5389.
12. Mukhopadhyay, B.; Maurer, S. V.; Rudolph, N.; van Well, R. M.; Russell, D. A.;
Field, R. A. J. Org. Chem. 2005, 70, 9059–9062.
13. For syntheses of Lea. See: (a) Lemieux, R. U.; Driguez, H. J. Am. Chem. Soc. 1975,
97, 4063–4068; (b) Jacquinet, J. C.; Sinay, P. J. Chem. Soc., Perkin Trans. 1 1979,
319–322; (c) Matta, K. L.; Rana, S. S. Carbohydr. Res. 1983, 117, 101–111; (d)
Marz, J.; Kunz, H. Synlett 1992, 589–590; (e) Yan, L.; Kahne, D. J. Am. Chem. Soc.
1996, 118, 9239–9248; (f) Ferla, B. L.; Prosperi, D.; Lay, L.; Russo, G.; Panza, L.
Carbohydr. Res. 2002, 337, 1333–1342.
(75 MHz, CDCl3):
d 170.7, 170.5, 170.4, 169.6, 169.5, 169.0,
139.3, 139.2, 139.0, 138.4, 135.3, 135.0, 132.5, 131.4, 129.1,
129.0, 128.9, 128.8, 128.5, 128.2, 128.1, 128.0, 127.9, 127.6,
124.4, 123.8, 99.4, 99.2, 98.0, 81.3, 76.9, 76.2, 75.4, 74.4, 74.0,
73.7, 73.3, 73.0, 72.9, 72.8, 71.6, 70.9, 70.6, 69.9, 68.6, 68.1,
67.0, 66.7, 61.0, 60.4, 56.5, 55.8, 55.4, 21.2, 21.0, 20.8, 17.4,
14.7; HRESIMS: m/z [M+Na]+ calcd for C63H69NO20Na:
1182.4305; found: 1182.4316.
14. (a) Spijker, N. M.; van Boeckel, C. A. A. Angew. Chem., Int. Ed. Engl. 1991, 30, 180–
183; (b) Ellervik, U.; Magnusson, G. J. Org. Chem. 1998, 63, 9314–9322.
15. Poletti, L.; Rencurosi, A.; Lay, L.; Russo, G. Synlett 2003, 15, 2297–2300.
16. Konradsson, P.; Mootoo, D. R.; McDevitt, R. E.; Fraser-Reid, B. J. Chem. Soc.,
Chem. Commun. 1990, 3, 270–272.