Synthesis of 2-(trimethylsilyl)ethyl α-D-mannopyranosides revisited

Article abstract of DOI:10.1081/CAR-120016846

Glycosylation of 2-(trimethylsilyl)ethanol with various ethyl 1-thioglycosides, which were activated with N-iodosuccinimide and silver triflate, was studied. The starting thioglycosides, some prepared for the first time, were obtained conventionally from the corresponding α-1-acetates. When β-1-acetates were more readily available, these were converted to the α-anomers by anomerization, prior to the glycosylation. Using ethyl 1-thioglycosides as glycosyl donors, especially those bearing a pivaloyl or a nonparticipating group at O-2, the corresponding 2-(trimethylsilyl)ethyl α-D-mannopyranosides were obtained in excellent yields.

Full text of DOI:10.1081/CAR-120016846

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SYNTHESIS OF 2-(TRIMETHYLSILYL)ETHYL α-d-
MANNOPYRANOSIDES REVISITED
b
Rina Saksena a , Jian Zhang a & Pavol Kováč
a NIDDK , LMC , National Institutes of Health , Bethesda, MD, 20892, U.S.A.
b NIDDK , LMC , National Institutes of Health , Bethesda, MD, 20892, U.S.A.
Published online: 16 Aug 2006.
To cite this article: Rina Saksena , Jian Zhang & Pavol Kováč (2002) SYNTHESIS OF 2-(TRIMETHYLSILYL)ETHYL α-d-
MANNOPYRANOSIDES REVISITED, Journal of Carbohydrate Chemistry, 21:6, 453-470
To link to this article: http://dx.doi.org/10.1081/CAR-120016846
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JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 21, No. 6, pp. 453–470, 2002
SYNTHESIS OF 2-(TRIMETHYLSILYL)ETHYL
a-D-MANNOPYRANOSIDES REVISITED
*
Rina Saksena, Jian Zhang, and Pavol Kova´cˇ
NIDDK, LMC, National Institutes of Health, Bethesda, MD 20892, USA
ABSTRACT
Glycosylation of 2-(trimethylsilyl)ethanol with various ethyl 1-thioglyco-
sides, which were activated with N-iodosuccinimide and silver triflate, was
studied. The starting thioglycosides, some prepared for the first time, were
obtained conventionally from the corresponding a-1-acetates. When b-1-
acetates were more readily available, these were converted to the a-anomers
by anomerization, prior to the glycosylation. Using ethyl 1-thioglycosides as
glycosyl donors, especially those bearing a pivaloyl or a nonparticipating
group at O-2, the corresponding 2-(trimethylsilyl)ethyl a-D-mannopyrano-
sides were obtained in excellent yields.
Key Words: 2-(Trimethylsilyl)ethyl glycosides; Glycosylation; NIS/AgOTf;
Anomerization
INTRODUCTION
The importance of 2-(trimethylsilyl)ethyl (SE) glycosides in the chemical
synthesis of oligosaccharides lies in the fact that they are stable during many
protecting group manipulations, yet the glycosidic 2-(trimethylsilyl)ethyl linkage can be
cleaved under conditions which leave interglycosidic linkages in oligosaccharides
(essentially) intact. A further desirable property of 2-(trimethylsilyl)ethyl glycosides is
that they can be converted to an array of other useful glycosyl derivatives.[1–4] While
*
Corresponding author.
453
DOI: 10.1081/CAR-120016846
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright D 2002 by Marcel Dekker, Inc.

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˘
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SAKSENA, ZHANG, AND KOVAC
454
good yields of 2-(trimethylsilyl)ethyl glycosides of most common sugars can be ob-
tained conventionally, synthesis of 2-(trimethylsilyl)ethyl a-D-mannopyranosides is no-
toriously problematic.[1,5]
The formation of 2-(trimethylsilyl)ethyl a-D-mannopyranosides from per-O-
acylated glycosyl chlorides has been studied.[5] Fully acylated mannopyranosyl
chlorides having different acyl groups at O-2 were treated with 2-(trimethylsilyl)ethanol
(SEOH) under the conditions of silver trifluoromethanesulfonate (triflate, AgOTf)
mediated Koenigs–Knorr reaction. The highest yield (72%) of the desired product was
obtained from 3,4,6-tri-O-acetyl-2-O-benzoyl-a-D-mannopyranosyl chloride, prepared
from 1,3,4,6-tetra-O-acetyl-2-O-benzoyl-b-D-mannopyranose (26).a Since the yield of
the fully benzoylated SE glycoside 11 from the corresponding glycosyl chloride was
only 48%, the author[5] concluded that it was not the presence of the benzoyl group at
O-2 alone, but ‘‘a proper ensemble of the protecting groups in a mannosyl donor’’ that
minimizes side reactions and, as a result, affects the yield of 2-(trimethylsilyl)ethyl a-D-
mannopyranosides. The same communication reported that, unlike with D-mannose, a
high yield of the corresponding 2-(trimethylsilyl)ethyl a-glycoside could be obtained
from the fully benzoylated L-rhamnose. Accordingly, we have been able to prepare 2-
(trimethylsilyl)ethyl 4-azido-3-O-benzyl-2-O-benzoyl-4,6-dideoxy-a-D-mannopyrano-
side (2),[6] from the corresponding glycosyl chloride, in 82% yield. However, the
need for a large quantity of 2, in connection with our synthesis of perosamine-
containing oligosaccharides suitable for conjugation,[7] rendered even this yield not
quite satisfactory. In an attempt to improve the yield, we have glycosylated SEOH
using ethyl 4-azido-3-O-benzyl-2-O-benzoyl-4,6-dideoxy-1-thio-a-D-mannopyranoside
(1) as a glycosyl donor and obtained the SE glycoside 2 in virtually theoretical yield.
That result prompted us to undertake the present study, and here we describe the
thioglycoside approach to making a number of useful 2-(trimethylsilyl)ethyl a-D-man-
nopyranosides. Because of the convenience[8] of its use, silver AgOTf/N-iodosucci-
nimide (NIS) reagent[9] was used as the promoter.
RESULTS AND DISCUSSION
Because of their versatility, thioglycosides have become very popular glycosyl
donors in glycoside synthesis. Nevertheless, to our knowledge, thioglycosides have not
been employed in syntheses of SE a-D-mannopyranosides. The ethyl 1-thio-D-manno-
pyranosides used during this work were conveniently prepared from the corresponding a-
1-O-acetyl derivatives. In the case of 30 and 31, the preparation was first carried out from
the more readily available b-1-acetates 26 and 27. When the yields of 30 and 31 were not
quite satisfactory we turned to conversions of the a-acetates 28 and 29, as it has been
reported[10] that the use of a-anomers resulted in shorter reaction times and cleaner
conversions to thioglycosides. In our situation, however, the benefit from the use of the a-
compounds was unimpressive. The a-1-acetates 28 and 29, were conveniently prepared
from the b-anomers 26 and 27 by treatment with a mixture of AcOH, Ac2O and H2SO4,
aNo physical constants or spectral data were reported for this substance, and the compound, as well
as its HO-2-free precursor, are erroneously shown (Ref. [5]) as a-anomers.

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2-(TRIMETHYLSILYL)ETHYL a-D-MANNOPYRANOSIDES
455
which is generally used to effect acetolysis. An equilibrium mixture was formed, con-
taining the a- and b-anomers in a ratio of ꢀ 93:7 (NMR). The pure a-anomers were then
obtained by chromatography, which also gave an unresolved mixture of anomers con-
taining a considerable amount of the b-anomer. The economy of preparation of the a-
anomers could be improved by repeated treatment of this unresolved mixture of anomers
with the acetolysis reagent (see above), to give product showing the same a:b ’ 93:7
ratio (NMR).
In the quest for improving the yield of 2 we treated ethyl 4-azido-2-O-benzoyl-
4,6-dideoxy-1-thio-a-D-mannopyranoside (1) with the NIS/AgOTf reagent and com-
pared the yield of the desired compound 2 with that obtained from 4-azido-2-O-
benzoyl-4,6-dideoxy-a-D-mannopyranosyl chloride.[6] Monitoring the reaction by thin-
layer chromatography (TLC) showed that 1.4 and 1.2 equivalents of NIS and AgOTf,
respectively, was necessary to drive the reaction to completion, and that the conversion
was a one-product reaction. After processing (see Experimental) and chromatography,
the desired SE glycoside 2 was obtained in virtually theoretical yield.
The above results suggested that high yields of other SE mannopyranosides might be
generally possible to obtain by way of 1-thioglycosides. Therefore, to ascertain if the
thioglycoside functionality alone caused the dramatic change of the situation, glycosy-
lation of SEOH with ethyl 2,3,4,6-tetra-O-acetyl-1-thio-a-D-mannopyranoside (4) was
carried out (since we do not deem this reaction to be preparatively useful, this experiment
is not described in the Experimental). Examination of the reaction mixture by TLC showed
that several products were formed, and that the desired SE glycoside (7) was present in
only a relatively small amount. The chromatographic mobility observed for two of the
byproducts isolated from this conversion indicated that they were the hemiacetal (8), and
2-(trimethylsilyl)ethyl 3,4,6-tri-O-acetyl-1-thio-a-D-mannopyranoside (9). This corre-
sponded to the previous observation[5] that products of partial deacetylation are formed
during reactions of acetylated glycosyl donors with SEOH (cf., also formation of 20 during
conversion 15! 19). Conventional acetylation of 9 gave the peracetate 7 (TLC, NMR).
To imitate the substitution pattern at positions 1 and 2 in 1, which gave the
optimum yield of the desired product, reaction of ethyl 2,3,4,6-tetra-O-benzoyl-1-thio-
a-D-mannopyranoside (10) with SEOH was examined next. Compound 10 was prepared
from ethyl 1-thio-a-D-mannopyranoside[11,12] (6), here obtained crystalline for the first
time. The NIS/triflic aciD-promoted[9] reaction of 10 with SEOH (not described in the
Experimental) was rather sluggish and yielded a multicomponent mixture. The same
conversion mediated with NIS/AgOTf [9] was virtually instantaneous, but 3.5 equiva-
lents of the promoter were required to leave only trace of the starting thioglycoside
unchanged. Analysis of the crude product by TLC showed the presence of two pro-

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´
SAKSENA, ZHANG, AND KOVAC
456
Table 1. Amounts of Reagents Used (mmol) in Reactions of 1 mmol of the Starting Thioglycoside
with 2 mmols of 2-(Trimethylsilyl)ethanol, and Yields (%) of Products
Thioglycoside
Product
NIS
1.2
AgOTf
1.4
Yield
ꢀ 100
1.5
3.5
3.5
1.5
1.5
1.5
1.6
3.5
3.5
1.5
1.5
1.9
ꢀ 20%
52.4
89
88.4
85.2
87
3

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2-(TRIMETHYLSILYL)ETHYL a-D-MANNOPYRANOSIDES
Table 1. Continued
457
Thyoglycoside
Product
NIS
2
AgOTf
2.2
Yield
73
1.3
1.2
1.2
1.2
71
66
32
ducts. After chromatography, the less polar product was shown to be the desired
compound 11, obtained in 52.4% yield. NMR and MS analysis of the more polar
material showed that it was the hemiacetal 12. The low yield of 11 from 10, which
compared well with that obtained[5] from the corresponding glycosyl chloride, indicated
that, as with 4 (vide supra), there was no advantage in the use of thioglycoside. Neither
did the use of a thioglycoside as a glycosyl donor change the situation in the con-
version 30 !32. Improved yield of the corresponding SE glycoside was not obtained,
compared to that from the glycosyl chloride.[5]
It has been suggested[5] that it is the hydrolysis of orthoesters, which are
intermediates in glycoside formation from 2-O-acylated glycosyl donors, that causes the
low yield of SE mannosides. Kunz[13] found that orthoester formation during gly-
cosylation is suppressed when 2-O-pivaloyl glycosyl donors are used, unlike with other
2-O-acylated glycosyl donors. When we treated the fully pivaloylated 1-thioglycoside
13 with 2-(trimethylsilyl)ethanol (see Experimental), the desired, hitherto unknown, SE
glycoside 14 was virtually the only product formed and, after chromatography, it was
isolated crystalline in excellent yield of 87%. In view of the above it was somewhat
disappointing to find that the yield of SE glycoside 33 from the 2-O-pivaloylated
thioglycoside 31, was not improved compared to that from 30.
The potential utility of 2-(trimethylsilylethyl) 3,4,6-tri-O-benzyl-a-D-mannopyr-
anoside (20) for making some (1 ! 2)-linked manno-oligosaccharides prompted us to
examine glycosylation of SEOH with ethyl 2-O-acyl-3,4,6-tri-O-benzyl-a-1-thio-D-

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SAKSENA, ZHANG, AND KOVAC
458
mannopyranosides 15, 17, and 18. The yields of the corresponding SE glycosides from
these glycosyl donors was high (> 80%). The best yield was obtained from the con-
version 18 !23, which was virtually a one product reaction, yielding 87% of 23, after
chromatography, along with a little of the corresponding b-anomer, 2-(trimethyl-
silyl)ethyl 2-O-pivaloyl-3,4,6-tri-O-benzyl-b-D-mannopyranoside 24.
R
R1
R2
R3
R4
R6
3
OAc
SEt
H
H
Ac
Ac
Ac
H
Ac
Ac
Ac
H
Ac
Ac
Ac
H
Ac
Ac
Ac
H
4
H
5
SEt
H
6
SEt
OSE
7
H
Ac
Ac
OH
Bz
Bz
Bz
Piv
Piv
Ac
H
Ac
Ac
Ac
Bz
Bz
Bz
Piv
Piv
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Bn
Bn
Bn
Ac
Ac
Ac
Ac
Ac
Bz
Bz
Bz
Piv
Piv
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Bn
Bn
Bn
Ac
Ac
Ac
Ac
Ac
Bz
Bz
Bz
Piv
Piv
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Bn
Bn
Bn
Ac
Ac
8
HOH
HOH
9
OSE
SEt
H
H
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
OSE
SEt
H
H
H
H
H
H
H
H
OSE
SEt
SEt
SEt
Bz
Piv
Ac
OH
Ac
Bz
Piv
Piv
H
SEt
OSE
OSE
HOH
OSE
OSE
H
H
H
OSE
Ac
Ac
Ac
H
H
H
Bz
Piv
Bz
Piv
Bz
Piv
Bz
Piv
Bn
Bn
Bn
Bz
Piv
H
Ac
Ac
SEt
SEt
OSE
OSE
SEt
OSE
H
H
H
H
H
H
H
H
OSE
SEt
SEt
H
H

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2-(TRIMETHYLSILYL)ETHYL a-D-MANNOPYRANOSIDES
459
Finally, we deemed it interesting to examine the formation of SE glycosides from
the fully benzylated mannosyl donor, ethyl 2,3,4,6-tetra-O-benzyl-1-thio-a-D-manno-
pyranoside (34). Since it contains only alkyl protecting groups, orthoester formation
during SE-glycoside formation can not occur. The conversion 34!35+36 was high
yielding, but produced the SE glycosides with impaired stereoselectivity.
Outcome of the reactions described above, together with the results of others[1,5]
confirm that formation of SE a-D-mannopyranosides is not a simple process. Although
it is not possible to make a simple generalization, the following observations have been
made. Firstly, the use of thioglycosides as glycosylating reagents for SEOH alone can
be beneficial, compared to the use of glycosyl chlorides.[5,6] For example, in the con-
version 1 !2, the use of ethyl 1-thioglycoside as the glycosyl donor, even with the 2-
O-benzoyl protection, resulted in a one-product reaction and a high yield of the desired
product. On the other hand, the use of thioglycosides had no significant effect on the
yield of 7 and 11 (see Experimental), compared to the use of glycosyl chlorides.[5,6]
Secondly, variously protected ethyl 1-thio a-D-mannopyranosides show different re-
activity when treated with the NIS/AgOTf reagent. Therefore, the amount of the NIS/
AgOTf reagent needed to drive the reaction to completion varied with the substitution
pattern, and it had to be determined for each ethyl 1-thioglycoside (Table 1). Pre-
sumably, the same holds also for other 1-thioglycosides. Thirdly, a comparison of
yields of the corresponding SE glycosides obtained from thioglycosides 4 and 13,
respectively, 52.4 and 89%, seems to suggest that formation and subsequent hydrolysis
of orthoesters during the formation of SE glycosides[5] is a factor that influences the
yield of SE mannopyranosides. It is, however, important to note in this context that
glycosylation of SEOH with 2-O-acetylated glycosyl donors does not necessarily result
in a poor yield of SE mannopyranosides (cf. the conversion 15! 19). Neither does the
presence of the O-pivaloyl group at position 2 in a glycosyl donor guarantee excellent
yield of the corresponding SE mannopyranoside (cf. the conversion 31!33). Thus,
besides simple orthoester formation and its hydrolysis, other phenomena must be
involved, which affect the yields of SE a-mannopyranosides. The results here described
suggest that these yields are affected not only by the nature of the acyl group at O-2,
but also by its presence/absence at position 6. This can be confidently concluded from
the yields of conversions of the tri-O-benzylated donors 15, 17, and 18, which all gave
very good yields of the corresponding SE glycosides, as well as from the comparison in
the yields of SE a-glycosides obtained from the mannoside 10 (52.4 or 48%[5]),
rhamnose[5] (86%), 1 ( ꢀ 100%), or the corresponding glycosyl chloride[6] (82%).
EXPERIMENTAL
General methods. Unless stated otherwise, optical rotations were measured at
ambient temperature for solutions in chloroform (c ꢀ 1), with a Perkin–Elmer auto-
matic polarimeter, Model 341. All reactions were monitored by TLC on Silica gel 60
coated glass slides (Whatman or Analtech). The judgment expressed in Results and
Discussion concerning the quality of individual reactions is based mainly on TLC and
not on the actual yields. Thus, a reaction is occasionally described as a ‘‘one-product
reaction,’’ even though the yield reported for that reaction is < 100%, which reflects
manipulative losses and not incomplete reactions or formation of by-products. Column
chromatography was performed by gradient elution from columns of silica gel. Solvent

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SAKSENA, ZHANG, AND KOVAC
460

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2-(TRIMETHYLSILYL)ETHYL a-D-MANNOPYRANOSIDES
461
mixtures slightly less polar than those used for TLC were used at the onset of elution.
Chemical ionization mass spectra (CIMS, positive or negative ion) were obtained on a
Finnigan 4000 quadrupole mass spectrometer with ammonia reagent gas. Fast atom
bombardment (FAB) mass data were obtained using a JEOL SX-102 mass spectrometer
Notes to Table 2:
aMeasured in CDCl3, unless stated otherwise; d, doublet; t, triplet; q, quartet; m, multiplet: b, broad;
po, partially overlapped; *not determined due to overlapping signals.
2
bdPhCH 4.73, 4.55 (2 d J 11.2 Hz).
2
cdCOCH 2.19s, 2.08s, 2.05s, 1.99s.
3
dMeasured in D2O.
e
d
3.76ddd J 6.2 and 9.7; d
3.51ddd; d
0.94m; d
ꢀ 0.0s; d
OCHaCH2Si
OCHbCH2Si
CH2CH2Si
(CH3)3Si
COCH3
2.12s, 2.06s, 2.01s, 1.96s.
fdCH CH Si 3.95dt, po, J 10.6 Hz; dCH CH Si 3.68dt, po, J 10.0 Hz; dCH CH Si 1.09m; d(CH ) Si 0.06s.
a
2
b
2
2
2
3 3
gData for the a-anomer. Measured after addition of D2O.
hdC(CH ) 1.28s, 1.24s, 1.17s, 1.12s.
3
3
i
d
3.82, 3.80 (2 t, J 10.0); d
3.56, 3.54 (2 t, J 10.0); d
0.99m; d
OCHaCH2Si
OCHbCH2Si
CH2CH2Si
(CH3)3Si
ꢀ 0.03s; dC(CH ) 1.27, 1.24, 1.16, 1.12, 4 s.
3
3
jdPhCH 4.84–4.48m.
2
kMeasured in C6D6. dPhCH 4.89, 4.59, 2d, J 11.3 Hz; 4.53, 4.40, 2d, J 12.0 Hz; 4.28s.
2
2
2
ldPhCH 4.85–4.46m; dCOCH 1.23s.
2
3
mMeasured in C6D6; dPhCH 5.03–4.34m; dCOCH 1.25s.
2
3
nMeasured in C6D6; dPhCH 5.05–4.38m; the signal of OCHaCH2Si appears as 2 t (d 3.83, 3.76), po
2
with the H-6a signal; the signal of OCHbCH2Si appears as 2 t at d 3.39 and 3.37, J 9.7 Hz; dCH CH Si
2
2
0.94–0.81m; d(CH ) Si ꢀ ꢁ 0.04s.
3
3
oMeasured in C6D6; dPhCH 4.81–4.41m; the signal of OCHaCH2Si appears as 2 t (d 3.84, 3.82), po
2
with the H-6b signal; the signal of OCHbCH2Si appears as 2 t at d 3.41 and 3.38, J 9.3 Hz; dCH CH Si
2
2
0.95–0.80m; d(CH ) Si ꢀ ꢁ 0.03s.
3
3
pdPhCH 4.83–4.44m; the signal of OCHaCH2Si is part of m at 3.85–3.69; dCH CH Si 3.49, 3.47
2
b
2
(2 t, J 9.8 Hz); dC(CH ) 1.19s; dCH CH Si 0.89m; d(CH ) Si ꢁ 0.02s.
3
2
2
3 3
4.87–4.44m; d3
3.99, 3.97 (2 t, J 9.3 Hz); d
3.58, 3.56 J 9.3 Hz); d
q
d
PhCH2
OCHaCH2Si
OCHbCH2Si
CH2CH2Si
0.93ddd, po, J 7.1 and 8.3; dC(CH ) 1.24s; d(CH ) Si 0.01s.
3
3
3 3
rdCOCH 2.15s, 2.07s, 2.05s, 1.99s.
3
sdCOCH 2.09s, 2.08s, 2.05s, 1.99s.
3
tMeasured in C6D6. dCOCH 1.79s, 1.68s, 1.63s, 1.50s.
3
udCOCH 2.18s, 2.09s, 2.05s, 1.99s; dC(CH ) 1.28s.
3
3 3
vdCOCH 2.13s, 2.07s, 1.97s.
3
wdCOCH 2.09s, 2.05s, 1.97s, 1.99s; dC(CH ) 1.28s.
3
3 3
xMeasured in C6D6; dCOCH 1.82s, 1.68s, 1.61s; dOCH CH Si, 3.69m; dOCH CH2Si, 3.30m; dCH CH2Si
3
a
2
b
2
0.89m; d(CH ) Si ꢀ 0.01s.
3
3
y
d
2.09s, 2.04s, 1.97s; d
3.81ddd; d
3.57ddd; d
0.99m; d
COCH3
OCHaCH2Si
OCHbCH2Si
CH2CH2Si
(CH3)3Si
0.04s; dC(CH ) 1.27.
3
3
zMeasured in C6D6; dCH Ph 4.99–4.34m, partially overlapped.
2
aaMeasured in C6D6; dPhCH 5.03–4.48m; the signal of OCHaCH2Si is part of m at 4.01–3.83; the
2
signal of OCHbCH2Si appears as m at 3.53–3.44; d dCH CH Si 0.96–0.90m; d(CH ) Si ꢀ 0.16s.
2
2
3 3
bb
d
5.02–4.39m; dOCH CH2Si 4.12–4.03m; the signal of OCHbCH2Si is part of m at 3.55–
PhCH2
a
3.43; dCH CH Si 1.0t; d(CH ) Si ꢀ 0.03s.
2
2
3 3
cc
d
d
2.12s, 2.05s, 1.97s.
2.08s, 2.04s, 1.96s.
COCH3
dd
COCH3

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SAKSENA, ZHANG, AND KOVAC
462
utilizing a glycerol matrix. Assignments of NMR signals (Tables 2–4), obtained at 300
1
MHz for H and 75 MHz for 13C at 25°C, were made by first-order analysis of spectra
and, when feasible, the assignments were supported by APT and/or DEPT experiments,
homonuclear decoupling and/or homo- and heteronuclear 2-dimensional correlation
spectroscopy. The commercial software supplied with the spectrometers (Varian
Gemini or Varian XL 300) was used. The b-anomeric configuration of substances was
ascertained by 1H–13C coupling constants[14] JC-1,H-1. Solutions in organic solvents
were dried with anhydrous Na2SO4 and concentrated at 40°C/2kPa.
Table 3. 1H NMR Coupling Constantsa for Compounds 1, 5–7, 10–14, 16, 18, 19, 22–24, and
26–38
Coupling Constants (Hz)
Compound
J1,2
1.6
J2,3
J3,4
J4,5
J5,6a
J5,6b
J6a,6b
1
3.2
3.5
3.3
3.1
3.1
3.3
3.1
3.3
3.1
3.1
3.6
*
9.9
9.9
6.2
6.1
2.7
6.0
2.6
*
5
1.1
ꢀ 1.2
1.4
10.1
ꢀ 9.8
10.2
ꢀ 10.0
ꢀ 10.3
10.2
9.9
10.1
ꢀ 9.8
10.2
ꢀ 10.0
ꢀ 10.3
ꢀ 10
10.1
9.6
2.6
6.4
2.3
4.5
5.0
3.5
1.9
2.0
1.9
1.7
1.9
1.5
1.7
1.7
*
12.4
12.5
12.5
12.4
ꢀ 13
12.2
12.5
12.5
11.1
10.9
10.9
11.0
10.8
10.8
*
6
7
10
11
12
13
14
16
16b
18
18b
19b
22b
23
24
26
27
28
29
30
31
32
33
34b
35b
36
37
38
ꢀ 1.0
1.8
1.8
2.6
4.4
4.4
4.5
4.8
4.3
4.6
4.6
4.6
*
1.6
1.7
9.9
9.3
1.4
1.5
9.3
9.2
9.2
1.5
1.8
*
9.2
*
9.2
2.9
3.3
2.6
3.3
3.0
3.5
3.2
3.3
3.0
3.5
3.1
*
1.8
1.8
9.2
ꢀ 9.2
9.7
*
9.1
1.9
*
9.3
ꢀ 1.0
0.9
1.2
9.3
2.3
5.5
5.0
4.7
4.0
5.0
4.7
4.9
5.3
5.2
*
4.3
2.3
2.2
2.5
2,4
2.4
2.3
2.5
2.6
1.6
3.8
5.9
2.5
2.2
*
10.3
10.1
10.2
10.0
10.0
10.0
*
ꢀ 10
9.8
13.0
12.7
12.3
12.2
12.3
12.2
12.1
12.4
10.9
ꢀ 10.7
10.6
12.2
12.7
2.0
2.1
10.2
10.0
10.0
9.9
1.8
ꢀ 1.6
ꢀ 1.5
1.9
*
9.9
2.9
3.2
3.1
3.1
3.5
3.3
*
1.4
10.0
9.3
10.0
9.6
ꢀ 1.4
0.8
1.1
9.3
9.3
2.0
5.5
5.6
10.0
10.0
10.1
10.0
0.9
aMeasured in CDCl3, unless stated otherwise.
bMeasured in C6D6.
*Not determined due to overlap, or broadening of signal, or second order effect.

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2-(TRIMETHYLSILYL)ETHYL a-D-MANNOPYRANOSIDES
463
NIS and AgOTf were purchased from Aldrich Chemical Company. Before use, NIS
was purified by crystallization from dioxane-CCl4, and dried at 80°C/2 kPa for 2 h, mp
201–202°C. Ethyl 2,3,4,6-tetra-O-acetyl-1-thio-a,b-D-mannopyranoside was obtained as
described,[15] except that the reaction was performed at room temperature. Essentially the
same anomeric mixture was formed within 3–4 h as that described[15] with the reaction
time 6–7 days. Chromatography and crystallization yielded the a-anomer 4, mp 106–
107°C (from EtOH), ref. 16, mp 107–108°C. The b-anomer 5 had mp 160–161°C (from
EtOH) and [a]D ꢁ 64° (c 0.9, CHCl3), in accord with literature values reported by Fried
and Waltz.[12] The NMR data, hitherto not reported, are in Tables 2–4. Ethyl 2,3,4,6-
tetra-O-benzoyl-1-thio-a-D-mannopyranoside (10) was obtained from 5 as described by
Sarbajna and Roy.[11] Ethyl 2,3,4,6-tetra-O-benzyl-1-thio-a-D-mannopyranoside (34) was
obtained from 6 as described by Helander et al.[16] 1,3,4,6-Tetra-O-acetyl-b-D-manno-
pyranose (25) was prepared as reported by Bovin et al.[17] Ethyl 2-O-benzoyl-3,4,6-tri-O-
benzyl-1-thio-a-D-mannopyranoside (17) was prepared according to Zhang et al.[18]
Ethyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-a-D-mannopyranoside (15) was obtained as
described.[19] The compound crystallized readily from isopropyl ether containing a few
drops of hexane, mp 51–53°C, ref. 19 mp 50–51°C. Deacetylation gave ethyl 3,4,6-tri-
O-benzyl-1-thio-a-D-mannopyranoside (16).[18]
General procedure for preparation of SE glycosides (for amounts of reagents
and yields of products, see Table 1). To a solution of the thioglycoside (1 mmol) in dry
CH2Cl2 (10 mL) was added 2-(trimethylsilyl) ethanol and molecular sieves (powder, 4
˚
A, 0.5 g), and the mixture was stirred for 15 min. N-Iodosuccinimide was added, which
resulted in slight pink color development. The stirring was continued for another
15 min, when AgOTf (0.1 M in toluene, freshly prepared and stored in the dark) was
added dropwise. Red color developed immediately upon the addition, and kept devel-
oping intermittently as the AgOTf solution was added, and it finally changed to yellow,
indicating that all starting material that had been activated with NIS was consumed.
TLC showed complete conversion of the starting material into the faster moving SE
glycoside and, occasionally, to more polar product(s). When conversion of the starting
material was incomplete, more NIS was added, followed by ‘‘titration’’ with the
solution of AgOTf. The reaction mixture was terminated by addition of triethylamine
(equimolar to AgOTf). The bright yellow precipitate formed was filtered through a pad
of Celite directly into a separating funnel containing excess of 2:1 (v/v) sodium
thiosulfate (10%)-sodium bicarbonate (satd) solution. The mixture was extracted with
CH2Cl2, the organic phase was dried, concentrated, and the crude product was
chromatographed. 2-(Trimethylsilyl)ethyl glycosides that were prepared following the
above protocol are listed below. In all glycosylations of SEOH, except for the con-
versions 1 !2, and 34!35 +36 a product more polar than the corresponding 1-thio-
ethyl glycoside, presumably[5] the product of hydrolysis of the starting glycosyl donor,
was formed.
Ethyl 4-azido-2-O-benzoyl-3-O-benzyl-4,6-dideoxy-1-thio- -D-mannopyrano-
side (1). Benzoyl chloride (0.12 mL, 1.02 mmol) was added to a solution of ethyl 4-
azido-3-O-benzyl-4,6-dideoxy-1-thio-a-D-mannopyranoside[20] (220 mg, 0.68 mmol) in
CH2Cl2 (3 mL) containing pyridine (0.17 mL, 2.03 mmol), and the mixture was stirred
for 3 h at room temperature. TLC (5:1 hexane-EtOAc) then showed that the reaction was

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SAKSENA, ZHANG, AND KOVAC
464
Table 4. 13C NMR Chemical Shifts for Compounds 1, 5–7, 10–14, 16, 18, 19, 22–24, and
26–38a
Compound
C-1
C-2
C-3
C-4
C-5
C-6
1b
82.31
82.54
84.40
96.99
82.35
97.10
92.28
82.47
97.22
83.35
84.24
82.45
83.31
98.26
98.18
97.18
98.56
90.48
90.38
91.30
90.57
82.24
82.17
97.43
96.86
82.77
98.49
101.16
82.78
82.64
69.76
70.39
72.00
69.81
72.14
70.77
70.96
71.06
69.75
69.85
70.57
69.91
70.84
69.73
70.17
68.31
67.71
68.70
70.75
69.79
67.90
71.64
70.68
70.93
69.30
77.89
76.49
73.91
71.12
70.15
76.45
71.81
71.26
69.13
70.50
70.11
69.89
69.82
69.40
80.42
81.50
78.77
79.89
79.30
79.37
78.42
80.57
70.75
65.16
69.91
69.09
69.60
69.77
69.93
69.42
81.64
81.51
82.33
72.09
72.09
64.55
65.79
67.28
66.27
67.07
67.08
66.83
65.32
65.32
74.49
75.60
74.38
75.42
75.58
75.44
74.32
74.30
65.31
67.83
66.25
65.24
66.31
65.97
66.82
65.94
76.10
76.19
74.96
65.84
65.51
67.51
76.58
73.22
68.4
18.57
62.75
61.01
62.63
62.88
63.10
62.70
62.08
62.19
68.83
70.07
68.91
70.02
70.25
70.26
69.11
69.15
61.97
61.83
62.52
61.86
62.36
62.16
62.86
62.36
70.34
70.67
69.74
62.80
62.56
5c
6d
7e
10f
11g
12h
13i
14j
16k
16l
18m
18n
19o
22p
23q
24s
26t
27u
28v
29w
30x
31y
32z
33aa
34bb
35cc
36dd
37ee
38ff
69.23
68.82
68.73
69.31
68.86
71.39
72.72
71.68
73.06
72.78
72.93
71.24r
75.46
73.02
72.88
71.65
70.50
68.90
68.73
69.43
68.31
73.39
73.40
75.88
76.37
76.07
aFor conditions of measurements, see Table 1.
bdPhCH 71.44; dSCH 25.67; dSCH CH 14.92.
2
2
2
cJC-1,H-1 151.4 Hz; dCH CH 14.92; dC3 H CH 25.78; dCOCH 20.65, 20.59, 20.51, 20.47.
2
3
2
3
3
ddSCH 24.94; dSCH CH 14.21.
edCH CH Si 65.81; d2CH CH Si 17.80; dSi(CH ) ꢁ 1.46; dCOCH 20.89, 20.70 (3 C).
2
3
2
2
3
3
3
3
3
fdSCH 25.61; dSCH CH 14.83.
2
2
3
gJC-1,H-1 171.2 Hz; dCH CH Si 66.16; dCH CH Si 17.99; d(CH ) Si ꢁ 1.40.
2
2
2
2
3 3
hJC-1,H-1 172.1 Hz.
idSCH 25.32; dSCH CH 14.75; dC(CH ) 39.05; dC(CH ) 38.88, 38.82, 38.75, 38.68; dC(CH ) 27.15,
27.09, 27.05, 27.02.
2
2
3
3
3
3
3
3 3
jJC-1,H-1 170.3 Hz; d
65.89; d
17.89; d
38.89, 38.86, 38.77, 38.72; d
CH2CH2Si
CH2CH2Si
C(CH3)3
C(CH3)3
27.14, 27.12, 27.09, 27.06; dSi(CH ) ꢁ 1.38.
3
3
kdCH CH 14.80; dCH CH 24.83; dCH Ph 75.07. 73.38, 72.00.
lMeasured in C6D6; dCH CH 15.25; dCH CH 25.27; dCH Ph 75.50. 73.88, 72.21.
mdPhCH 75.10, 73.14; 71.37; dCH CH 14.96; dCH CH 25.45; dC(CH ) 39.05; dC(CH ) 27.11.
2
3
2
3
2
2
3
2
3
2
2
2
3
2
3
3
3
3 3

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2-(TRIMETHYLSILYL)ETHYL a-D-MANNOPYRANOSIDES
465
complete and that one product was formed. A little ice, followed by saturated, aqueous
NaHCO3 was added, and the mixture was stirred for 2 h. After extraction with CH2Cl2,
the organic phase was concentrated, and the residue was chromatographed, to give
amorphous 1 (285 mg, 98%), [a]D +65° (c 1.45); CIMS: m/z 445 ([M +18] + ).
Anal. Calcd for C22H25N3O4S: C, 61.81; H, 5.89; N 9.83; S, 7.50. Found: C,
61.98; H, 6.00; N 9.9.76; S, 7.60.
2-(Trimethylsilyl)ethyl 4-azido-2-O-benzoyl-3-O-benzyl-4,6-dideoxy- -D-man-
nopyranoside (2). The conversion 1!2 was a one product reaction. Chromato-
graphy gave, in virtually theoretical yield, compound 2, which was identical with the
independently synthesized substance (NMR, mp), obtained previously[6] in 82% yield.
Ethyl 1-thio- -D-mannopyranoside (6). Conventional deacetylation (Zemple´n)
of 4 gave the title compound 6, mp 126–127°C (from EtOH), [a]D +20.2° (c 0.85, H2O).
Anal. Calcd for C8H16O5: C, 42.84; H,7.19. Found: C, 42.75; H, 6.94.
2-(Trimethylsilyl)ethyl 2,3,4,6-tetra-O-benzoyl- -D-mannopyranoside (11).
One major and a minor product were formed. Chromatography gave first the
amorphous 11, [a]D ꢁ 42.4° (c 1.5). CIMS: m/z 714 ([M +18] + ).
Notes to Table 4 Continued:
nMeasured in C6D6. dPhCH 75.64, 73.68; 72.00; dCH CH 15.30; dCH CH 25.97; dC(CH ) 39.39;
2
2
3
2
3
3 3
dC(CH ) 27.69.
3
3
oMeasured in C6D6; dPhCH 75.65, 73.91, 72.27; dCH CH Si 65.64; dCH CH Si 18.37; dCOCH 20.99;
2
2
2
2
2
3
dSi(CH ) ꢁ 0.99.
3
3
pMeasured in C6D6; dPhCH 75.68, 73.93, 72.08; dCH CH Si 65.72; dCH CH Si, 18.35; dSi(CH ) ꢁ 0.96.
2
2
2
2
2
3 3
qdPhCH 75.11, 73.16; 71.24; dCH CH Si 65.11; dCH CH Si 17.84; dC(CH ) 38.94; dC(CH ) 27.12;
2
2
2
2
2
3
3
3 3
dSi(CH ) ꢁ 1.41.
3
3
r2-Carbon signal.
sJC-1,H-1 154.7 Hz; dPhCH 75.08, 73.23; 71.00; dCH CH Si 67.05; dCH CH Si 17.86; dC(CH ) 39.01;
2
2
2
2
2
3 3
dC(CH ) 27.22; dSi(CH ) ꢁ 1.35.
3
3
3 3
tdCOCH 20.59 (2 C), 20.54, 20.45.
3
uJC-1,H-1 162.4 Hz;dCOCH 20.56 (2 C), 20.40, dC(CH ) 39.15, dC(CH ) 26.98.
3
3
3
3 3
vMeasured in C6D6 JC-1,H-1 177.8 Hz; dCOCH 20.63, 20.52 (2 C), 20.30.
3
wdCOCH 20.85, 20.58 (2 C), 20.54; dC(CH ) 39.06; dC(CH ) 26.99.
3
3
3
3 3
xJC-1,H-1 168.5 Hz;dCOCH 20.59, dCH CH 14.74, dCH CH 25.52.
3
2
3
2
3
yJC-1,H-1 168.5 Hz; dCOCH 20.60, 20.55, 20.49, dCH CH S 14.76, dCH CH S 25.40; dC(CH ) 39.02.
3
2
3
2
3
3 3
zMeasured in C6D6; dCOCH 20.36, 20.23 (2C) dCH CH Si 65.85; dCH CH Si 17.84; dSi(CH )3 ꢁ 1.38.
3
2
2
2
2
3
aa
d
20.60, 20.55, 20.51; dCH CH Si 65.72; dCH CH Si 17.73; dC(CH )3 38.95; dSi(CH )3 ꢁ 1.52.
2 3 2 3 2
COCH3
bbMeasured in C6D6; dCH CH 15.52, dCH CH 25.78, dP2hCH 75.55, 73.82, 72.87; 72.49.
2
2
2
3
3
ccMeasured in C6D6; JC-1,H-1 166.0 Hz; dPhCH 75.57, 73.90, 73.52, 72.62; dCH CH Si 65.34;
2
2
2
dCH CH Si 18.45; dSi(CH ) ꢁ 0.93.
2
2
3 3
dd
J
153.5 Hz; dPhCH 75.12, 73.78, 73.43, 71.31; dCH CH Si 67.19; dCH CH Si 18.28,
C-1,H-1
2
2
2
2
2
dSi(CH ) ꢁ 1.39.
3
3
ee
ff
J
153.9 Hz; dCOCH 20.72, 20.66, 20.60; dCH CH 14.89, dCH CH 25.91.
C-1,H-1
3
2
3
2
3
J
154.1 Hz; dC(CH ) 39.10; dC(CH ) 27.06; dCH CH 14.90; dCH CH 25.95; dCOCH 20.67,
C-1,H-1
3
3
3
3
2
3
2
3
3
20.64, 20.50.

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SAKSENA, ZHANG, AND KOVAC
´
466
Anal. Calcd for C39H40O10Si: C, 67.72; H, 5.79. Found: C, 66.86; H, 5.86.
Eluted next was 2,3,4,6-tetra-O-benzoyl-a,b-D-mannopyranose (12), which was
identified by comparison with an authentic sample,[21] (TLC, NMR); CIMS: m/z 614
([M+ 18] + ).
Ethyl 2,3,4,6-tetra-O-pivaloyl-1-thio- -D-mannopyranoside (13). Pivaloylation
of 6, as described below for preparation of 18, gave the title ethyl 1-thioglycoside 13 in
92% yield, mp 104–105°C (from EtOH), [a]D + 58° (c 0.9); CIMS: m/z 578 ([M+ 18] + ).
Anal. Calcd for C28H48O9S: C, 59.97; H, 8.63. Found: C, 60.12; H, 8.65.
2-(Trimethylsilyl)ethyl 2,3,4,6-tetra-O-pivaloyl- -D-mannopyranoside (14).
One major product, faster moving than the starting material, and one minor, slower
moving product was formed, as shown by TLC (30:1 toluene–acetone). Chromatogra-
phy gave 14, mp 82–84°C (from EtOH containing a few drops of water, [a]D +33.5°
(c 0.9); FAB MS: m/z 455 ([M + Na] + ).
Anal. Calcd for C31H56O10Si: C, 60.36; H, 9.15. Found: C, 60.32; H, 9.14.
Ethyl 3,4,6-tri-O-benzyl-2-O-pivaloyl-1-thio- -D-mannopyranoside (18). Piva-
aloyl chloride (1.2 mL, 10 mmol) was added with stirring to a solution of ethyl 3,4,6-
tri-O-benzyl-1-thio-a-D-mannopyranoside[18] (16, 2.36 g, 5 mmol) in pyridine (1.2 mL,
15 mmol), and the mixture was stirred at room temperature with exclusion of
atmospheric moisture overnight. TLC (15:1 hexane–acetone) showed that the reaction
was complete and that one product was formed. Aqueous NaHCO3 solution was added, to
destroy excess of the reagent, and the mixture was partitioned between CH2Cl2 and
aqueous NaHCO3 solution. The organic phase was dried, concentrated, and chroma-
tography gave amorphous compound 18 (3.10 g, 87%), [a]D + 71° (c 0.9); CIMS: m/z 596
([M+ 18] + ).
Anal. Calcd for C34H42O6S: C, 70.56; H, 7.31. Found: C, 70.77; H,7.41.
2-(Trimethylsilyl)ethyl 2-O-acetyl-3,4,6-tri-O-benzyl- -D-mannopyranoside
(19). One major and three minor products were formed. Eluted first was the title com-
pound 19, [a]D + 29° (c 2.8), CIMS: m/z 591 ([M-1]).
Anal. Calcd for C33H44O7Si: C, 68.89; H, 7.48. Found: C, 68.98; H, 7.51.
Two of the three minor products formed were isolated in amounts sufficient to be
identified by MS and NMR spectroscopy. Eluted next was the product of deacetylation
of the major product 19, 2-(trimethylsilyl)ethyl 3,4,6-tri-O-benzyl-a-D-mannopyrano-
1
side (20, ꢀ 20 mg). H NMR (CDCl3): d 4.91 (d, 1 H, J1,2 1.7 Hz, H-1); 13C NMR
(CDCl3): d 98.68 (JC-1,H-1 168.6 Hz, C-1), 80.27 (C-3), 75.10, 73.40, 71.91 (3 CH2Ph),
73.37 (C-4), 70.93 (C-5), 68.96 (C-6), 68.51 (C-2), 64.88 (OCH2CH2Si), 17.85
(CH2Si), ꢁ 1.37[(CH3)3]; FAB MS: m/z 573 ([M +Na] + ), which was not further char-
acterized. When this material was acetylated, the product was indistinguishable from
compound 19 described above (TLC, NMR, MS).
Eluted last was the hemiacetal 21, as indicated by its chromatographic mobility
and m/z value 515 ([M +Na] + ) in the FAB MS spectrum.
2-(Trimethylsilyl)ethyl 2-O-benzoyl-3,4,6-tri-O-benzyl- -D-mannopyranoside
(22). One major product, faster moving that the starting material, and one minor,

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2-(TRIMETHYLSILYL)ETHYL a-D-MANNOPYRANOSIDES
467
slower moving product was formed, as shown by TLC (40:1 toluene–acetone). Chro-
matography gave the amorphous 22, [a]D ꢁ 2.3° (c 3.4); CIMS: m/z 672 ([M+ 18] + ).
Anal. Calcd for C39H46O7Si: C, 71.53; H, 7.08. Found: C, 71.55; H, 7.17.
2-(Trimethylsilyl)ethyl 3,4,6-tri-O-benzyl-2-O-pivaloyl- -D-mannopyranoside
(23). Three products were formed, the one showing the fastest chromatographic mo-
bility largely predominating. Chromatography (25:1 toluene–EtOAc) gave first the title
glycoside 23, [a]D + 29° (c 0.9); CIMS: m/z 652 ([M+ 18] + ).
Anal. Calcd for C37H50O7Si: C, 70.00; H, 7.94. Found: C, 70.06; H, 7.82.
Eluted next was a small amount of material whose NMR spectra showed it to be
2-(trimethylsilyl)ethyl 3,4,6-tri-O-benzyl-2-O-pivaloyl-b-D-mannopyranoside (24).
1,3,4,6-Tetra-O-acetyl-2-O-benzoyl- -D-mannopyranose (26). Benzoylation of
25,[17] as described above for the preparation of 1 gave 26 in virtually theoretical yield,
mp 103–104°C (from EtOH), [a]D ꢁ 65° (c 0.8); CIMS: m/z 470 ([M + 18] + ).
Anal. Calcd for C21H24O11: C, 55.75; H, 5.35 Found: C, 55.68; H, 5.35.
1,3,4,6-Tetra-O-acetyl-2-O-pivaloyl- -D-mannopyranose (27). A reaction of
the 2-hydroxy compound 25 with pivaloyl chloride, as described above for similar
benzoylation gave, after chromatography, the title derivative 27 in virtually theo-
retical yield, mp 106–107°C (from EtOH), [a]D ꢁ 20.4° (c 0.8); CIMS: m/z 455
([M +18] + ).
Anal. Calcd for C19H28O11: C, 52.77; H, 6.53. Found: C, 52.91; H, 6.47.
1,3,4,6-Tetra-O-acetyl-2-O-benzoyl- -D-mannopyranose (28). A solution of
26 (1 g) in 10:4:0.1 Ac2O:AcOH:H2SO4 (6 mL) was kept at room temperature over-
night. TLC (3:1 hexane–acetone) showed that a faster moving product was formed.
1H NMR showed that a ꢀ 93:7 equilibrium mixture of a- and b-anomers was pre-
sent.b Solid NaOAc trihydrate was added with stirring, to neutralize the mineral acid,
followed by aqueous NaHCO3, to destroy Ac2O and neutralize AcOH. The resulting
mixture was partitioned between CH2Cl2 and aqueous NaHCO3 solution, the organic
phase was dried, concentrated, and chromatography gave first the pure a-anomer 28
(0.83 g, 83%), mp 102–103°C (from EtOH), [a]D ꢁ 15° (c 0.8); FAB MS: m/z 475
([M +Na] + ).
Anal. Calcd for C21H24O11: C, 55.75; H, 5.35 Found: C, 55.72; H, 5.35.
Eluted next was a mixture of a- and b-anomers. Such mixtures, obtained from several
experiments, could be processed as described above, to obtain more of the desired 28.
1,3,4,6-Tetra-O-acetyl-2-O-pivaloyl- -D-mannopyranose (29). Anomerization
of 27, as described above for the preparation of 26 gave, after chromatography, the
amorphous 29 (90%), [a]D + 42° (c 0.8); CIMS: m/z 455 ([M+ 18] + ).
Anal. Calcd for C19H28O11: C, 52.77; H, 6.53. Found: C, 52.79; H, 6.65.
bThat ratio had not changed when, in a separate experiment, the reaction time was extended to 48 h,
1
as showed by H NMR spectroscopy. The two anomers show almost identical mobility on TLC.

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SAKSENA, ZHANG, AND KOVAC
´
468
Ethyl 3,4,6-tri-O-acetyl-2-O-benzoyl-1-thio- -D-mannopyranoside (30). A.
From 1,3,4,6-Tetra-O-acetyl-2-O-benzoyl-b-D-mannopyranose (26). Ethanethiol (0.45
mL, 3 mmol) followed by BF3-etherate (1.5 mL) was added at 0°C, with stirring and
exclusion of moisture, to a solution of 26 (1.35 g, 3 mmol) in CH2Cl2 (60 mL), and the
mixture was kept in a refrigerator (5–7°C) until TLC (3:1 hexane–acetone) showed
that almost all starting material was consumed ( ꢀ 3 days). One major and several
minor products were formed. The mixture was slowly poured into aqueous NaHCO3,
contained in a separatory funnel, the product was extracted with CH2Cl2, and chro-
matography gave first the a-anomer 30 (0.785 g, 58%), mp 66–67°C (from EtOH),
[a]D +127° (c 1.7); CIMS: m/z 472 ([M +18] + ).
Anal. Calcd for C21H26O9S: C, 55.50; H, 5.77. Found: C, 55.62; H, 5.90.
Eluted next was a small amount of material whose NMR spectra showed it to be
ethyl 3,4,6-tri-O-acetyl-2-O-benzoyl-1-thio-b-D-mannopyranoside (37, 45 mg, 3%);
CIMS: m/z 472 ([M + 18] + ).
B. From 1,3,4,6-tetra-O-acetyl-2-O-benzoyl-a-D-mannopyranose (28). The reac-
tion of 28, performed on the same scale as described above but with only 1.2 mL of
BF3-etherate, was terminated after ꢀ 24 h. Chromatography gave 30 and 37 in 65 and
2% yield, respectively.
Ethyl 3,4,6-tri-O-acetyl-2-O-pivaloyl-1-thio- -D-mannopyranoside (31). A.
From 1,3,4,6-Tetra-O-acetyl-2-O-pivaloyl-b-D-mannopyranose (27). The reaction, car-
ried out as described above for the preparation of 30 (B) gave, after a reaction time
of 48 h and chromatography, the a-anomer 31 (680 mg, 52%), 93.5–94°C, [a]D +90°
(c 0.8). CIMS: m/z 452 ([M +18] + ).
Anal. Calcd for C19H30O9S: C, 52.52; H, 6.96. Found: C, 52.53; H, 7.03.
Eluted next was the amorphous ethyl 3,4,6-tri-O-acetyl-2-O-pivaloyl-1-thio-b-D-
mannopyranoside (38, 300 mg, 23%), [a]D ꢁ 76° (c 1.6); CIMS: m/z 452 ([M+ 18] + ).
Found: C, 53.02; H, 6.77.
B. From 1,3,4,6-tetra-O-acetyl-2-O-pivaloyl-a-D-mannopyranose (29). Reaction as
above (A) gave compounds 31 and 38 in 60 and 12%, respectively.
2-(Trimethylsilyl)ethyl 3,4,6-tri-O-acetyl-2-O-benzoyl- -D-mannopyranoside
(32). One major and one minor product were formed. Chromatography (5:1 he-
xane–acetone) gave 32, [a]D +15.5° (c 0.5); CIMS: m/z 528 ([M+ 18] + ).
Anal. Calcd for C24H34O10Si: C, 56.45; H, 6.71. Found: C, 56.51; H, 6.61.
2-(Trimethylsilyl)ethyl 3,4,6-tri-O-acetyl-2-O-pivaloyl- -D-mannopyranoside
(33). One major and one minor product were formed. Chromatography (10:1 toluene–
acetone) gave 33 [a]D +53° (c 1.1); CIMS: m/z 508 ([M+ 18] + ).
Anal. Calcd for C22H38O10Si: C, 53.86; H, 7.81. Found: C, 53.77; H, 7.80.
2-(Trimethylsilyl)ethyl 2,3,4,6-tetra-O-benzyl- - (35) and b-D-mannopyrano-
side (36). Two products, which showed similar chromatographic mobility were
formed, as shown by TLC (10:1 hexane–EtOAc). The a-anomer 35, eluted first,
showed [a]D + 48° (c 0.7). FABMS: m/z 663 ([M +Na] + ).
Anal. Calcd for C39H48O6Si: C, 73.09; H,7.55. Found: C, 73.03; H,7.70.

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2-(TRIMETHYLSILYL)ETHYL a-D-MANNOPYRANOSIDES
469
The b-anomer 36,which was eluted next, crystallized on standing. Recrystalliza-
tion from EtOH gave material melting at 56–59°C, [a]D ꢁ 13.5° (c 0.3), FABMS: m/z
663 ([M + Na] + ). Found: C, 73.16; H, 7.70.
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Received March 14, 2002
Accepted June 27, 2002