Chemoselective Glycosylations. 2. Differences in Size of Anomeric Leaving Groups Can Be Exploited in Chemoselective Glycosylations

Article abstract of DOI:10.1021/jo971233k

We have developed a novel chemoselective glycosylation strategy. This glycosylation strategy is based on the fact that the glycosyl reactivity of an anomeric thiol group can be controlled by the bulkiness of this group whereby we have produced a new range of differentially reactive coupling substrates. It was also shown that the anomeric configuration of the thioglycosides affects the reactivity of the substrates. The new approach will enable complex oligosaccharides of biological importance to be prepared in a highly convergent manner. The versatility of this approach is demonstrated by the synthesis of pentasaccharide 34 from the building blocks 7, 9, 10, 12, and 14 without a single protecting group manipulation.

Full text of DOI:10.1021/jo971233k

J . Org. Chem. 1997, 62, 8145-8154
8145
Ch em oselective Glycosyla tion s. 2. Differ en ces in Size of
An om er ic Lea vin g Gr ou p s Ca n Be Exp loited in Ch em oselective
Glycosyla tion s
Richard Geurtsen,† Duncan S. Holmes,‡ and Geert-J an Boons*,†
School of Chemistry, The University of Birmingham, Edgbaston Birmingham B15 2TT, U.K., and
GlaxoWellcome, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, U.K.
Received J uly 7, 1997
We have developed a novel chemoselective glycosylation strategy. This glycosylation strategy is
based on the fact that the glycosyl reactivity of an anomeric thiol group can be controlled by the
bulkiness of this group whereby we have produced a new range of differentially reactive coupling
substrates. It was also shown that the anomeric configuration of the thioglycosides affects the
reactivity of the substrates. The new approach will enable complex oligosaccharides of biological
importance to be prepared in a highly convergent manner. The versatility of this approach is
demonstrated by the synthesis of pentasaccharide 34 from the building blocks 7, 9, 10, 12, and 14
without a single protecting group manipulation.
In tr od u ction
been demonstrated5 that saccharides may be regarded
as disarmed when a cyclic acetal is attached to the
pyranosyl ring. Recently, Ley and co-workers reported
that thioglycosides, bearing a dispiroketal (dispoke)6 or
cyclohexanone-1,2-diacetal (CDA) protecting group,7 have
reactivities between armed and disarmed thioglycosides
and therefore may be regarded as semi-disarmed sub-
strates. Thus, at the moment three distinct levels of
anomeric reactivity for thioglycosides have been de-
scribed.
The anomeric reactivity of the glycosyl donors reported
hitherto is controlled by protecting groups only, in
particular the one at C-2. This feature imposes a serious
limitation since the nature of the protecting group at C-2
is a major determinant of the stereochemical outcome of
a glycosylation. Therefore, it will be attractive to control
the anomeric reactivity of thioglycosyl donors by other
means, for example by modifying the anomeric leaving
group. Such an approach will give an exciting op-
portunity to tune glycosyl donor leaving group ability
further and, thus, realize a greater potential for these
glycosylation reactions.8
Oligosaccharides are involved in many vital biological
processes, and not surprisingly, there is increased de-
mand for new and more efficient methods for their
chemical synthesis.1 During the past few years, thiogly-
cosides2 and n-pentenyl glycosides3 have attracted con-
siderable attention in oligosaccharide synthesis. These
substrates are stable under many different chemical
conditions, and thus, the anomeric moiety can act as an
efficient protecting group. In addition, in the presence
of several electrophilic reagents, thio- and n-pentenyl
glycosides are activated and undergo clean glycosylations
with a variety of glycosyl acceptors. Another attractive
feature of thio- and n-pentenyl glycosides is that they can
be used in a chemoselective (“armed-disarmed”) glyco-
sylation strategy.3,4 In such a glycosylation strategy,
protecting group manipulations are avoided during the
assembly of an oligosaccharide, and hence the number
of synthetic steps can be limited.
The armed-disarmed glycosylation approach relies on
the fact that C-2 ethers activate (arm) and C-2 esters
deactivate (disarm) the anomeric center. Thus, coupling
of a glycosyl donor having a C-2 ether protecting group
(armed) with an acceptor having a C-2 ester protecting
group (disarmed) proceeds highly chemoselectively to give
a coupling product in high yield. The anomeric center
of the resulting disarmed disaccharide can be activated
with a more powerful activator, and reaction with a
suitable acceptor will yield a trisaccharide. It has also
Here, we report the effect of the bulkiness of the
anomeric thiol group on glycosyl reactivity whereby we
have produced a new range of differentially reactive
coupling substrates.9
Resu lts a n d Discu ssion
It was anticipated that structural and electronic modi-
fications of an anomeric moiety of a thioglycoside will
(5) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J .
Am. Chem. Soc. 1988, 110, 5583.
(6) Boons, G. J .; Grice, P.; Leslie, R.; Ley, S. V.; Yeung, L. L.
Tetrahedron Lett. 1993, 34, 8523.
(7) Ley, S. V.; Priepke, H. W. M. Angew. Chem., Int. Ed. Engl. 1994,
33, 2292.
(8) For a review on strategies for oligosaccharide synthesis, see:
Boons, G. J . Tetrahedron 1996, 52, 1095. For chemoselective and
orthogonal glycosylations, see: Friesen, R. W.; Danishefsky, S. J . J .
Am. Chem. Soc. 1989, 111, 6656. Mehta, S.; Pinto, B. M. Tetrahedron
Lett. 1991, 32, 4435. Roy, R.; Andersson, F. O.; Letellier, M. Tetrahe-
dron Lett. 1992, 33, 6053. Raghavan, S.; Kahne, D. J . Am. Chem. Soc.
1993, 115, 1580; Mehta, S.; Pinto, B. M. J . Org. Chem. 1993, 58, 3269.
Sliedregt, L. A. J . M.; Zegelaar-J aarsveld, K.; van der Marel, G. A.;
van Boom, J . H. Synlett 1993, 335. Yamada, H.; Harada, T.; Miyazaki,
H.; Takahashi, T. Tetrahedron Lett. 1994, 35, 3979. Kanie, O.; Ito, Y.;
Ogawa, T. J . Am. Chem. Soc. 1994, 116, 12073.
† The University of Birmingham.
‡ GlaxoWellcome, Medicines Research Centre.
Abstract published in Advance ACS Abstracts, October 15, 1997.
(1) (a) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155. (b)
Paulsen, H. Ibid. 1990, 29, 823. (c) Schmidt, R. R. Ibid. 1986, 25, 212.
(d) Schmidt, R. R. Pure Appl. Chem. 1989, 61, 1257. (e) Sinay¨, P. Ibid.
1991, 63, 519. (f) Nicolaou, K. C.; Caulfield, T. J .; Croneberg, R. D.;
Ibid. 1991, 63, 555. (g) Vasella, A. Ibid. 1991, 63, 507. (h) Fraser-Reid,
B.; Udodong, U. E.; Wu, Z. F.; Ottoson, H.; Merritt, J . R.; Rao, S.;
Roberts, C.; Madsen, R. Synlett 1992, 12, 927. (i) Toshima, K.; Tatsuta,
K. Chem. Rev. 1993, 93, 1503.
(2) Fugedi, P.; Garegg, P. J .; Lo¨hn, H.; Norberg, T. Glycoconjugate
J . 1987, 4, 97.
(3) Fraser-Reid, B.; Udodong, U. E.; Wu, Z.; Ottosson, H.; Merritt,
J . R.; Rao, C. S.; Roberts, C.; Madsen, R. Synlett 1992, 927-942.
(4) (a) Veeneman, G. H.; van Boom, J . H. Tetrahedron Lett. 1990,
31, 275. (b) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J . H.
Tetrahedron Lett. 1990, 31, 1331.
(9) Boons, G. J .; Geurtsen, R.; Holmes, D. Tetrahedron Lett. 1995,
36, 6325.
S0022-3263(97)01233-4 CCC: $14.00 © 1997 American Chemical Society

8146 J . Org. Chem., Vol. 62, No. 23, 1997
Geurtsen et al.
Sch em e 1
F igu r e 1. Synthesis of glycosyl donors and acceptors.
effect the anomeric leaving group ability. The glycosyl
donors and acceptors 3, 4, 7, and 9 were prepared to
investigate the effect of the bulkiness of the anomeric
thiol group on the anomeric reactivity (Figure 1). Treat-
ment of peracetylated glucose with dicyclohexylmethane-
thiol10 in the presence of trimethylsilyl triflate (TMSOTf)
for 16 h at 20 °C gave, after aqeuous workup and
trituration, two fractions that contained the individual
anomers of 1 which were further purified by silica gel
column purification to give pure 1R (49%) and 1â (18%).
Compound 1R was deacetylated with NaOMe in dichlo-
romethane (DCM)/methanol to give 2R which was sub-
sequently benzylated with benzyl bromide and sodium
hydride in DMF to afford 3R in an excellent yield (77%).
Compound 4R was obtained by benzoylation of 2R with
benzoyl chloride in pyridine. The 6-hydroxyl of 2R was
regioselectively protected as a tert-butyldimethylsilyl
ether (TBDMS) by treatment with TBDMSCl in pyridine
to furnish compound 5R (76%). Compound 5R was
benzylated with sodium hydride and benzyl bromide in
DMF to afford 6R (92%), the TBDMS group of which was
removed by treatment with acetic acid-water (9/1, v/v)
at 60 °C to yield compound 7R (76%). Compound 8R was
obtained by benzoylation of 5R with benzoyl chloride in
pyridine and removal of the TBDMS group with acetic
acid/water (9/1, v/v) at 60 °C gave compound 9R (76%
overall yield). The â-anomers of compounds 3, 4, 7, and
9 were obtained by employing similar reaction sequences
but starting from the â-anomer of 1.
Having the requisite glycosyl donors and acceptors in
hand, attention was focused on chemoselective glycosy-
lations. Iodonium dicollidine perchlorate (IDCP)-medi-
ated glycosylation of glycosyl donor 10 with glycosyl
acceptor 7R in ether/DCM gave, after a reaction time of
2 h, disaccharide 11 in a yield of 40% as one anomer
(Scheme 1). Some starting material and a small amount
of a trisaccharide (3%) was isolated. Furthermore, it was
observed that side products appeared after an aqueous
workup procedure, probably resulting from hydrolytic
degradation. Attempts to prevent the formation of these
side products failed. The coupling reaction could also be
performed with the more convenient activator system
NIS/TfOH, but in this case only 1% of TfOH was used
(10% TfOH is used under standard conditions). The use
of a larger amount of acid gave a mixture of products.
To the best of our knowledge, this is the first example
which demonstrates that the bulk of the anomeric leaving
group has a profound effect on leaving group mobility,
and the new methodology makes it now possible to couple
chemoselectively benzylated thioglycosyl donors with
benzylated thioglycosyl acceptors. This feature is of
particular importance when in the subsequent glycosy-
lation an R-anomeric linkage needs to be introduced.
In the next stage of the research, we examined whether
electronically and sterically deactivated substrates have
sufficiently different reactivities to perform chemoselec-
tive glycosylations. Thus, coupling of the electronically
deactivated glycosyl acceptor 12 with the sterically
deactivated glycosyl donor 11R in the presence of the
powerful promoter system N-iodosuccinimide/triflic acid
(NIS/TfOH) afforded trisaccharide 13 in a 70% yield. A
reasonable R-selectivity was obtained (R/â ) 6/1) when
the reaction was performed in a solvent mixture contain-
ing equal amounts of diethyl ether and DCM. However,
this selectivity could be significantly improved (R/â ) 12/
1) by increasing the proportion of diethyl ether (diethyl
ether/DCM 5/1, v/v). In this respect, it is noteworthy that
coupling of dicyclohexylmethyl 2,3,4,6-tetra-O-benzyl
thioglucoside (3) with acceptor 12 in a mixture of diethyl
ether/DCM (1/1 v/v) gave the expected disaccharide in
high yield but with modest anomeric selectivity (R/â )
3/1). Thus, the glycosyl moiety at C-6 of disaccharide 11
affects the stereochemical course of the glycosylation, and
a much improved R-selectivity is obtained. This direc-
tional effect probably originates from additional steric
hindering at the â-face of the glycosyl donor. It has been
reported11
that bulky protecting groups at C-6 of a
glucosyl donor improve the R-selectivity.
A different reaction profile was obtained when trisac-
charide 13 was prepared from the â-linked dicyclohexyl-
methyl thioglycoside 7â. Thus, coupling of the ethyl
thioglycoside 10 with 7â in the presence of IDCP gave
the disaccharide 11â in a high yield of 71%. No self-
condensed or polymeric products were detected, and apart
from the disaccharide 11â only small amounts of starting
materials were isolated. The improved yield may prob-
ably be attributed to the lower reactivity of the â-linked
thiodicyclohexylmethyl moiety. The trisaccharide 13 was
isolated in a disappointing yield of 30% when the coupling
was performed with 11â as the glycosyl donor. In this
(10) Dicyclohexylmethanethiol was prepared from the corresponding
commercial available alcohol according to the three-step procedure of
Kellogg et al.: Strijtveen, B.; Kellogg, R. M. J . Org. Chem. 1986, 51,
3664.
(11) Houdier, S.; Vottero, P. J . A. Carbohydr. Res. 1992, 232, 349.

Chemoselective Glycosylations
J . Org. Chem., Vol. 62, No. 23, 1997 8147
Ta ble 1
Sch em e 2
R/â ratio of 3
product yield (%)
recovered donor 3 (%)
1/0
1/1
0/1
50 (R/â ) 3/1)
44 (R/â ) 3/1)
37 (R/â ) 3/1)
42 (R/â ) 1/0)
54 (R/â ) 3/1)
53 (R/â ) 0/1)
case, a substantial amount of glycosyl donor 11â was
recovered, and it proved to be difficult to drive the
reaction successfully to completion.
The results of these glycosylations demonstrate that
the reactivity of a C-2-benzylated dicyclohexylmethyl
thioglycoside is of an order of magnitude between ethyl
thioglycosides having a fully armed ether and disarmed
ester protecting group on C-2 which implies that these
novel thioglycosides may be regarded as semi-disarmed
substrates. However, it appeared that the reactivity of
these novel compounds (7 and 11) depends on the
anomeric configuration of the thio moiety. To study this
observation further, the R- and â-anomers of 3 were
coupled with 14, but in these experiments only 0.7 equiv
of NIS was used. As can be seen from Table 1, the
R-anomer gave a higher conversion than the â-anomer.
As expected, a significant amount of donor was reclaimed,
Sch em e 3
1
the H NMR spectrum of which showed that no anomer-
ization of the anomeric thio leaving group had occurred.
This observation is in agreement with an earlier report12
which described that thioglycosides having a bulky
anomeric thio group do not anomerize during iodonium
ion promoted glycosylations. The latter property pro-
vided the possibility to compare directly the reactivities
of R- and â-thioglycosides by a competitive glycosylation.
When a mixture of anomers of 3 (R/â )1/1) was glycosy-
lated with 14, using 0.7 equiv of NIS, mainly the
â-anomer of 3 (R/â ) 1/3) was reclaimed and largely the
R-anomer had been glycosylated. The latter reaction was
also performed as a NMR experiment which showed a
similar conversion. It was also observed that treatment
of compound 7R with IDCP resulted, after a reaction time
of 2 h, in a complex mixture of products containing self-
condensed and hydrolyzed material and some 1,6-anhy-
dro-2,3,4-tri-O-benzyl-glucose. Interestingly, no reaction
was observed when the analogous â-anomer was treated
with IDCP. These observations indicated that it should
be possible to couple chemoselectively glycosyl donor 3R
with 7â to give 11â. Indeed, when a mixture of 3R and
7â was treated with IDCP, disaccharide 11â was isolated
in a yield of 50% (Scheme 2).
bulky thioglycosides is that during glycosylation only the
R- and â-anomer glycosyl halides are in a dynamic
equilibrium.
With a novel method at our disposal to control the
anomeric leaving group mobility, it should be possible to
create glycosyl donors or acceptors with new reactivities.
We envisaged that the sterically and electronically
deactivated glycosyl acceptor 9 should have a lower
reactivity than the electronically deactivated glycosyl
donor 16. Indeed, coupling of glycosyl donor 16 with
glycosyl acceptor 9R in the presence of NIS/TMSOTf at
rt gave disaccharide 17R in a 64% yield (Scheme 3). A
small amount of a trisaccharide was formed (3%) which
was easily removed by size-exclusion column chromatog-
raphy. To demonstrate that an electronically and steri-
cally deactivated substrate is still a suitable glycosyl
donor, compound 17R was coupled with 14 in the pres-
ence of NIS/TMSOTf at room temperature and trisac-
charide 18 was isolated in a good yield (73%). In this
case, an excess of NIS had to be used to drive the reaction
to completion. When trisaccharide 17 was prepared from
glycosyl acceptor 9, having the anomeric thio moiety in
the â-configuration, a less satisfactory result was ob-
tained and coupling of 16 with 9â under standard
conditions gave 17â in a modest yield of 41%; a significant
amount of self-condensation was observed. Disaccharide
On the basis of the outcome of these reactions, it can
be concluded that the R-linked benzylated dicyclohexyl-
methyl thioglycosides are more reactive than the corre-
sponding â-anomers. Lemieux and co-workers have
reported13 that the R- and â-anomers of glycosyl bromides
have significantly different reactivities, and this property
has been exploited for the synthesis of R-glycosides (in
situ anomerization procedure). However, the main dif-
ference between the reactivities of glycosyl halides and
(12) Boons, G. J .; Stauch, T. Synlett 1996, 906.
(13) (a) Lemieux, R. U.; Hayimi, J . L. Can. J . Chem. 1965, 43, 2162.
(b) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; J ames, K. J . Am.
Chem. Soc. 1975, 97, 4056.

8148 J . Org. Chem., Vol. 62, No. 23, 1997
Geurtsen et al.
Ta ble 2
Sch em e 5
R/â ratio of 4
product yield (%)
recovered donor 4 (%)
1/0
1/1
0/1
30 (â only)
45 (â only)
56 (â only)
64 (R/â ) 1/0)
52 (R/â ) 1/3)
38 (R/â ) 0/1)
Sch em e 4
α
17â could easily be glycosylated with 14 under standard
conditions to give 18 in a good yield (73%).
These results indicate that the reactivity of acetylated
dicyclohexylmethyl thioglycosides is also effected by the
anomeric configuration. Indeed, NIS/TMSOTf-mediated
glycosylation of an anomeric mixture of 4 (R/â )1/1) with
14 gave, apart from the expected product 19, recovery of
4 mainly as the R-anomer (R/â )3/1) (Table 2). Further-
more, it was observed that these thioglycosides do not
anomerize during the glycosylation. Thus, these experi-
ments clearly indicate that a benzoylated dicyclohexyl-
methyl thioglycoside having a â-configuration is signifi-
cantly more reactive than the analogous R-anomer. The
corresponding benzylated substrates (Table 1) showed an
inverse reactivity; i.e. the R-anomer is more reactive. The
differences in reactivity between benzylated and benzoy-
lated thioglycosides may be rationalized as follows: the
benzoyl protecting group at C-2 of a â-substituted dicy-
clohexylmethyl thioglycoside will, after activation with
an iodonium ion, assist the departure of the anomeric
thio group by neighboring group participation. In the
case of the R-anomer, neighboring group participation
may take only place after an unfavorable conformational
change of the pyran ring. In the case of a C-2-benzylated
dicyclohexylmethyl thioglycoside, additional stabilization
of a transition state may only be achieved by participa-
tion of a lone pair of the endocyclic oxygen. Thus, in the
case of the R-anomer, the developing positive charge at
the anomeric center may be stabilized by the lone pair
of the endocyclic oxygen. This stabilization of the â-ano-
mer is only possible after an unfavorable conformational
change, and hence the R-anomer is more reactive.
Encouraged by the promising results obtained, we
explored glycosylations with the less reactive glycosyl
acceptors. The glucosides 23 and 24 having a 4-hydroxyl
were selected as this position has the lowest glycosyl
acceptor reactivity and hence represents a worse case
scenario. Compound 23 was easily obtained from 2 via
a three-step procedure (Scheme 4). Thus, treatment of
2 with benzaldehyde dimethyl acetal and a catalytic
amount of camphorsulfonic acid gave regioselectively the
partially protected saccharide 20. Benzylation of 20
under standard conditions afforded the fully protected
compound 21, and regioselective reductive cleavage14 of
the benzylidene acetal of 21 with triethylsilane (TES) and
trifluoracetic acid (TFA) yielded the required glycosyl
acceptor 23. Compound 20 was also the starting material
for the preparation of glycosyl acceptor 24. Thus, ben-
zoylation of 20 with benzoyl chloride in pyridine gave 22,
the benzylidene acetal of which was regioselectively
cleaved by treatment with NaCNBH4 and HCl to yield
24.
IDCP-mediated glycosylation of the activated glycosyl
donor 10 with the sterically deactivated acceptor 23 in a
DCM/diethyl ether mixture gave the disaccharide 25 as
a single anomer in an acceptable yield of 40% (Scheme
5). No self-condensed or oligomeric material was ob-
tained, and apart from the coupling product, some
starting material was recovered together with hydrolyzed
material. As expected, coupling of the sterically deacti-
vated glycosyl donor 3R with the electronically deacti-
vated acceptor 26 proceeded in good yield to give disac-
charide 27 (61%, R/â ) 6/1) when the promoter system
NIS/TfOH was used. Unfortunately, the coupling of the
electronically deactivated substrate 16 with the doubly
deactivated acceptor 24 did not result in the formation
of disaccharide 29, and mainly hydrolyzed donor and
acceptor 24 were isolated (Scheme 6). The 4-hydroxyl of
24 is deactivated by the neighboring benzoyl protecting
group and by the presence of the anomeric thio moiety.
Also the benzoylated donor is of low reactivity. The
reaction may proceed more favorably with the glycosyl
donor 28, which by the presence of the benzyl ethers at
C-3, C-4, and C-6 is significantly more reactive than 16.
However, the acetyl functionality at C-2 of 28 will have
a disarming effect and will perform neighboring group
participation to give a â-glycoside. The coupling of 28
with 24 in the presence of NIS/TfOH gave only a small
amount of coupling product 30 (19%). Fortunately, when
(14) DeNinno, M. P.; Etienne, J . B.; Duplantier, K. C. Tetrahedron
Lett. 1995, 36, 669.

Chemoselective Glycosylations
Sch em e 6
J . Org. Chem., Vol. 62, No. 23, 1997 8149
Sch em e 7
applicable to primary as well as secondary sugar hy-
droxyls, and it appeared that the R-anomers of dicyclo-
hexylmethyl thioglycosides provide the most versatile
substrates. The armed-disarmed glycosylation strategy
has gained in versatility since the anomeric reactivity of
glycosyl donors and acceptors can now be controlled by
the bulkiness of the leaving group as well as the nature
of protecting groups. A wider range of di- and trisac-
charides can now be prepared by chemoselective glyco-
sylations having differing anomeric configuration. Such
saccharides will be valuable for the assembly of complex
oligosaccharides. The methodology is also reliable when
performed with larger fragments.
TMSOTf was used instead of triflic acid, the reaction
proceeded smoothly and disaccharide 30 was isolated in
a yield of 56%. Finally, it was demonstrated that a
doubly deactivated glycosyl donor reacts cleanly with a
stericly hindered sugar alcohol and NIS/TMSOTf-medi-
ated coupling 4R with the methyl glucoside 31 gave the
disaccharide 32 in an excellent yield of 62%.
A combined use of electronic and steric factors enables
the generation of a range of thioglycosides with four
distinct levels of anomeric reactivity, and it should now
be possible to assemble a pentasaccharide from properly
protected thioglycosides without any protecting group
manipulations. To illustrate the latter feature, the
pentasaccharide 34 was prepared from the building
blocks 7R, 9R, 10, 12, and 14 (Schemes 1 and 7). The
electronically deactivated trisaccharide donor 13 was
coupled with the doubly disarmed glycosyl acceptor 9R
in the presence of the powerful promoter NIS/TMSOTf
to give the tetrasaccharide 33 in a reasonable yield of
55%. In this case, only the â-anomer was obtained as a
result of neighboring group participation of the C-2
benzoyl ester of 13. Finally, NIS/TMSOTf-mediated
glycosylation of 33 with 14 afforded the pentasaccharide
34 in a yield of 62%. The successful preparation of 34
illustrates that the chemoselective glycosylation meth-
odology proceeds reliably also when performed with
larger fragments.
Exp er im en ta l Section
Gen er a l Meth od s. Column chromatography was per-
formed on silica gel 60 (Merck, 70-230 mesh), and reactions
were monitored by TLC on Kieselgel 60 F254 (Merck). Detec-
tion was effected by examination under UV light and by
charring with 20% sulfuric acid in methanol, or with a
molybdate solution (a 0.02 M solution of ammonium cerium-
(IV) sulfate dihydrate and ammonium molybdate(VI) tetrahy-
drate in aqueous 10% H2SO4). Solvents were evaporated under
reduced pressure at 40 °C (bath). All solvents were distilled
from the appropriate drying agents; dichloromethane, 1,2-
dichloroethane, and toluene were distilled from P2O5 and
stored over molecular sieves (4 Å). Diethyl ether was distilled
from CaH2, redistilled from LiAlH4, and stored over sodium
wire. N,N-Dimethylformamide was stirred with CaH2 for 16
h, distilled under reduced pressure, and stored over molecular
sieves (4 Å). Methanol was dried by refluxing with magnesium
methoxide, distilled, and stored over molecular sieves (3 Å),
and pyridine was dried by refluxing with CaH2 and then
distilled and stored over molecular sieves (4 Å).
Con clu sion
The research described in this paper shows, for the first
time, that the reactivity of thioglycosides can be con-
trolled by the bulkiness of the anomeric thiol group and
has produced glycosyl donors and acceptors with new
levels of reactivity. It was also shown that the anomeric
configuration of the thioglycosides affects the reactivity
of the substrates. The new methodology proved to be
Dicycloh exylm eth yl 2,3,4,6-Tetr a -O-a cetyl-1-th io-r/â-
D-glu cop yr a n osid e (1). To a stirred mixture of â-D-glucose
pentaacetate (15.2 g, 38.9 mmol) and dicyclohexylmethanethiol
(7.1 g, 33.4 mmol) in dry CH2Cl2 (70 mL) was added TMSOTf
(7.8 mL, 42.8 mmol). After 16 h of stirring at rt, the reaction

8150 J . Org. Chem., Vol. 62, No. 23, 1997
Geurtsen et al.
mixture was quenched with TEA (6.2 mL, 44.5 mmol), diluted
with CH2Cl2 (50 mL), and washed with H2O (3 × 25 mL). The
organic layer was dried (MgSO4) and filtered. The filtrate was
concentrated in vacuo and triturated from CH2Cl2/petroleum
ether (bp 40-60 °C) to afford a mixture of 1â and peracetylated
glucose. Further purification by silica gel column chromatog-
raphy (toluene/acetone, 95/5, v/v) afforded 1â as a white solid
40-60 °C), 8/1, v/v) to afford 4R as a white glass (2.2 g, 82%):
Rf 0.60 (CH2Cl2/petroleum ether (bp 40-60 °C), 9/1, v/v); [R]25
D
+8.52° (c 1); FAB-MS m/z 813 (M+ + Na); 13C NMR (CDCl3) δ
166.3-165.3 (4 C6H5CO), 133.4-128.4 (4 C6H5CO), 86.0 (C-
1), 71.8, 70.8, 69.4 and 68.7 (C-2,3,4,5), 62.9 (C-6), 62.0 (SCH),
1
41.1-26.1 (2 C6H11); H NMR (CDCl3), δ 8.10-7.30 (m, 20H,
4 C6H5CO), 6.01 (t, 1H, H-3, J 2,3 10.5, J 3,4 10.0 Hz), 5.73 (d,
1H, H-1, J 1,2 5.7 Hz), 5.72 (t, 1H, H-4, J 4,5 9.8 Hz), 5.47 (dd,
1H, H-2), 4.86 (m, 1H, H-5, J 5,6a 2.8, J 5,6b 4.1 Hz), 4.59 (dd,
1H, H-6a, J 6a,6b -12.3 Hz), 4.50 (dd, 1H, H-6b), 2.40-0.60 (m,
23H, SCH, 2 C6H11); HR FAB-MS calcd for C25H48SSiO5Na
511.2889, found 511.2866. Dicyclohexylmethyl 2,3,4,6-tetra-
O-benzoyl-1-thio-â-D-glucopyranoside (4â) was obtained by the
same synthetic procedure, starting from 2â, as a white solid:
Rf 0.60 (CH2Cl2/petroleum ether (bp 40-60 °C), 9/1, v/v); [R]D
+0.90° (c 1); 13C NMR (CDCl3) δ 166.3-165.3 (4 C6H5CO),
133.4-128.3 (4 C6H5CO), 87.9 (C-1), 76.2, 74.2, 71.7 and 70.1
(C-2,3,4,5), 63.8 (C-6), 62.5 (SCH), 41.1-26.1 (2 C6H11); 1H
NMR (CDCl3) δ 8.10-7.20 (m, 20H, 4 C6H5CO), 5.91 (t, 1H,
H-3/4, J 9.6 Hz), 5.63-5.49 (m, 2H, H-3/4 and H-2), 4.76 (d,
1H, H-1, J 1,2 9.9 Hz), 4.60 (dd, 1H, H-6a, J 5,6a 2.9, J 6a,6b -12.2
Hz), 4.51 (dd, 1H, H-6b, J 5,6b 6.2 Hz), 4.13 (m, 1H, H-5, J 4,5
9.6 Hz), 2.30-0.60 (m, 23H, CHS, 2 C6H11).
(3.3 g, 18%): Rf 0.45 (toluene/acetone, 9/1, v/v); [R]25 -0.23°
D
(c 1); FAB-MS m/z 465 (M+ + Na); 13C NMR (CDCl3) δ 170.6-
169.3 (4 COCH3), 87.1 (C-1), 75.6, 74.1, 71.2, and 68.7
(C-2,3,4,5), 62.6 (C-6), 62.2 (SCH), 40.8-26.3 (2 C6H11), 20.7-
1
20.6 (4 COCH3); H NMR (CDCl3) δ 5.20 (t, 1H, H-3, J 2,3J 3,4
9.3 Hz), 5.04 (t, 1H, H-4, J 4,5 9.7 Hz), 4.96 (dd, 1H, H-2, J 1,2
10.1 Hz), 4.40 (d, 1H, H-1), 4.20 (dd, 1H, H-6a, J 5,6a 5.7, J 6a,6b
-12.2 Hz), 4.11 (dd, 1H, H-6b, J 5,6b 2.5 Hz), 3.63 (m, 1H, H-5),
2.28 (m, 1H, SCH), 2.07, 2.06, 2.02, and 2.00 (4 s, 12 H, 4
COCH3), 1.90-1.00 (m, 22H, 2 C6H11); HR FAB-MS calcd for
C
27H42SO9Na 565.2447, found 565.2461. The remaining fil-
trate was concentrated in vacuo, and the residue was purified
by silica gel column chromatography (toluene/acetone, 95/5,
v/v) to afford 1R as a white solid (8.8 g, 49%): Rf 0.53 (toluene/
acetone, 9/1, v/v); [R]25 +11.35° (c 1); 13C NMR (CDCl3), δ
D
170.6-169.3 (4 COCH3), 85.1 (C-1), 70.8, 70.4, 68.6 and 68.0
(C-2,3,4,5), 62.0 (C-6), 61.2 (SCH), 41.3-26.5 (2 C6H11), 20.8-
Dicycloh exylm et h yl 6-O-(ter t-Bu t yld im et h ylsilyl)-1-
th io-r-D-glu cop yr a n osid e (5r). Compound 2R (910 mg, 2.43
mmol) was dissolved in dry pyridine (20 mL), and TBDMSCl
(386 mg, 2.56 mmol) was added. The mixture was stirred for
18 h at rt, diluted with CH2Cl2 (50 mL), and washed with H2O
(3 × 15 mL). The organic layer was dried (MgSO4) and filtered.
The filtrate was concentrated in vacuo and co-concentrated
from toluene, MeOH, and CH2Cl2, respectively (3 × 15 mL
each). Purification of the residue by silica gel column chro-
matography (CH2Cl2/acetone, 5/1, v/v) afforded 5R (1.12 g, 76%)
as a white glass: Rf 0.28 (CH2Cl2/MeOH, 9/1, v/v); [R]D +5.56°
(c 1); FAB-MS m/z 511 (M+ + Na); 13C NMR (CDCl3) δ 89.3
(C-1), 75.2, 72.4, 72.1, and 71.0 (C-2,3,4,5), 62.2 (C-6), 61.9
(SCH), 41.3, 39.7, and 32.0-26.5 (2 C6H11), 26.0 (SiC(CH3)3),
18.4 (SiC(CH3)3), -5.4 (Si(CH3)2); 1H NMR (CDCl3), δ 5.21 (d,
1H, H-1, J 1,2 5.4 Hz), 4.02 and 3.71-3.36 (m, 4H, H-2,3,4,5),
3.93 (dd, 1H, H-6a, J 5,6a 4.1, J 6a,6b -10.4 Hz), 3.76 (dd, 1H,
H-6b, J 5,6b 6.1 Hz), 2.36 (m, 1H, SCH), 2.00-1.00 (m, 22H, 2
C6H11), 0.92 and 0.91 (2 s, 9H, SiC(CH3)3), 0.11 and 0.10 (2 s,
6H, Si(CH3)2); HR FAB-MS calcd for C25H48SSiO5Na 511.2889,
found 511.2866. Dicyclohexylmethyl 6-O-(tert-butyldimethyl-
silyl)-1-thio-â-glucopyranoside (5â) was obtained by the same
synthetic procedure, starting from 2â, as a white glass: Rf 0.23
(CH2Cl2/MeOH, 9/1, v/v); [R]D -0.87° (c 1); 13C NMR (CDCl3)
δ 88.5 (C-1), 78.1, 77.8, 73.5, and 72.6 (C-2,3,4,5), 64.7 (C-6),
61.0 (SCH), 41.1, 40.0 and 31.9-26.4 (2 C6H11), 25.8 (SiC-
1
20.7 (4 COCH3); H NMR (CDCl3) δ 5.48 (d, 1H, H-1, J 1,2 5.8
Hz), 5.33 (dd, 1H, H-3, J 2,3 10.5, J 3,4 9.4 Hz), 5.05 (t, 1H, H-4,
J 4,5 10.2 Hz), 5.00 (dd, 1H, H-2), 4.48 (m, 1H, H-5, J 5,6a 4.0,
J 5,6b 2.1 Hz), 4.33 (dd, 1H, H-6a, J 6a,6b -12.4 Hz), 4.02 (dd,
1H, H-6b), 2.34 (m, 1H, SCH), 2.09, 2.07, 2.04, and 2.01 (4 s,
12H, 4 COCH3), 1.90-1.00 (m, 22H, 2 C6H11).
Dicycloh exylm eth yl 2,3,4,6-Tetr a -O-ben zyl-1-th io-r-D-
glu cop yr a n osid e (3r). To a solution of 1R (6.5 g, 12.0 mmol)
in dry CH2Cl2/MeOH (2/1, v/v, 90 mL) was added NaOMe (75
mg, 1.4 mmol). The solution was stirred for 3 h, neutralized
with Dowex-50 (H+) resin, and filtered. The filtrate was
concentrated in vacuo and co-concentrated from CH2Cl2 (2 ×
20 mL) to yield 2R as a white solid (4.5 g, 100%), Rf 0.59 (CH2-
Cl2/MeOH, 4/1, v/v). To a solution of 2R (1.2 g, 3.2 mmol) in
dry DMF (20 mL) were added NaH (614 mg, 26 mmol) and
BnBr (2.3 mL, 19.3 mmol). The mixture was stirred for 18 h
at rt, diluted with EtOAc (50 mL), and washed with H2O (3 ×
20 mL). The organic layer was dried (MgSO4) and filtered.
The filtrate was concentrated in vacuo and co-concentrated
from toluene, MeOH, and CH2Cl2 (3 × 15 mL each). Purifica-
tion of the residue by silica gel column chromatography (CH2-
Cl2/petroleum ether (bp 40-60 °C), 3/1, v/v) afforded compound
3R as a white solid (1.8 g, 77%): Rf 0.41 (CH2Cl2/petroleum
ether (bp 40-60 °C), 4/1, v/v); [R]25D +8.68° (c 1); FAB-MS m/z
757 (M+ + Na); 13C NMR (CDCl3), δ 138.9, 138.0, 137.9, and
128.4-127.5 (4 C6H5CH2), 86.1 (C-1), 82.8, 80.0, 77.7 and 70.9
(C-2,3,4,5), 75.3, 73.6, 73.2, and 72.2 (4 C6H5CH2), 68.5 (C-6),
59.2 (SCH), 41.4-26.5 (2 C6H11); 1H NMR (CDCl3) δ 7.42-
7.09 (m, 20H, 4 C6H5), 5.30 (d, 1H, H-1, J 1,2 3.3 Hz), 5.01-
4.62 (m, 8H, 4 C6H5CH2), 4.25 (m, 1H, H-5), 3.87-3.55 (m,
5H, H-2, H-3, H-4, H-6a, H-6b), 2.43-0.97 (m, 23H, SCH and
2 C6H11); HR FAB-MS calcd for C47H58SO9Na 757.3903, found
757.3890. Dicyclohexylmethyl 2,3,4,6-tetra-O-benzyl-1-thio-
â-D-glucopyranoside (3â) was obtained by the same synthetic
procedure, starting from 1â, as a white solid: Rf 0.41 (CH2-
1
(CH3)3), 18.2 (SiC(CH3)3), -5.5 (Si(CH3)2); H NMR (CDCl3) δ
4.25 (d, 1H, H-1, J 1,2 9.8 Hz), 3.90 (dd, 1H, H-6a, J 5,6a 4.9, J 6a,6b
-10.4 Hz), 3.80 (dd, 1H, H-6b, J 5,6b 6.1 Hz), 3.7-3.3 (m, 4H,
H-2,3,4,5), 2.41 (m, 1H, SCH), 1.90-1.00 (m, 22H, 2 C6H11),
0.91 and 0.90 (2 s, 9H, SiC(CH3)3), 0.10 and 0.09 (2 s, 6H, Si-
(CH3)2).
Dicycloh exylm et h yl 2,3,4-Tr i-O-b en zyl-6-O-(ter t-b u -
tyld im eth ylsilyl)-1-th io-r-D-glu cop yr a n osid e (6r). To a
solution of 5R (365 mg, 0.75 mmol) in dry DMF (10 mL) was
added NaH (104 mg, 4.50 mmol) and BnBr (0.40 mL, 3.38
mmol). After 18 h of stirring at rt, the reaction mixture was
diluted with EtOAc (50 mL) and washed with H2O (3 × 15
mL). The organic layer was dried (MgSO4) and filtered. The
filtrate was concentrated in vacuo and co-concentrated from
toluene, MeOH, and CH2Cl2, respectively (3 × 15 mL each).
Purification by silica gel column chromatography (CH2Cl2/
petroleum ether (bp 40-60 °C), 3/2, v/v) afforded 6R as a
colorless syrup (307 mg, 92%): Rf 0.70 (CH2Cl2/petroleum ether
Cl2/petroleum ether (bp 40-60 °C), 4/1, v/v); [R]25 +0.42° (c
D
1); 13C NMR (CDCl3) δ 138.7, 138.4, 138.2, and 128.5-127.6
(4 C6H5CH2), 88.4 (C-1), 87.0, 82.8, 78.9, and 78.0 (C-2,3,4,5),
75.8, 75.7, 75.0, and 73.7 (4 C6H5CH2), 69.5 (C-6), 61.0 (SCH),
1
41.4-26.3 (2 C6H11); H NMR (CDCl3), δ 7.45-7.15 (m, 20H,
4 C6H5), 4.98-4.52 (m, 8H, 4 C6H5CH2), 4.34 (d, 1H, H-1, J 1,2
9.5 Hz), 3.71-3.35 (m, 6H, H-2, H-3, H-4, H-5, H-6a, H-6b),
2.44-1.10 (m, 23H, SCH, 2 C6H11).
Dicycloh exylm eth yl 2,3,4,6-Tetr a -O-ben zoyl-1-th io-r-
D-glu cop yr a n osid e (4r). To a solution of 2R (1.27 g, 3.39
mmol) in dry pyridine (30 mL) were added DMAP (42 mg, 0.34
mmol) and BzCl (2.2 mL, 19.0 mmol). After 18 h of stirring
at rt, the reaction mixture was diluted with CH2Cl2 (50 mL)
and washed with H2O (3 × 20 mL). The organic layer was
dried (MgSO4) and filtered. The filtrate was concentrated in
vacuo and co-concentrated from toluene, MeOH, and CH2Cl2,
respectively (3 × 25 mL each). The residue was purified by
silica gel column chromatography (CH2Cl2/petroleum ether (bp
(bp 40-60 °C), 1/1, v/v); [R]25 +6.00° (c 1); FAB-MS m/z 781
D
(M+ + Na); 13C NMR (CDCl3) δ 138.8, 138.6, 138.4, and 128.5-
127.6 (3 C6H5CH2), 88.3 (C-1), 87.0, 82.9, 80.0, and 77.7 (C-
2,3,4,5), 75.9, 75.7, and 75.0 (3 C6H5CH2), 62.5 (C-6), 60.7
(SCH), 41.5, 39.8, and 31.9-26.5 (2 C6H11), 26.0 (SiC(CH3)3),
1
18.3 (SiC(CH3)3), -5.1 and -5.5 (Si(CH3)2); H NMR (CDCl3)
δ 7.42-7.25 (m, 15H, 3 C6H5CH2), 5.02-4.81 (m, 6H, 3
C6H5CH2), 4.32 (d, 1H, H-1, J 1,2 9.9 Hz), 3.84-3.19 (m, 6 H,
H-2, H-3, H-4, H-5, H-6a, H-6b), 2.41 (m, 1H, SCH), 1.99-
1.00 (m, 2 C6H11), 0.90 (s, 9H, SiC(CH3)3), 0.09 and 0.06 (2 s,

Chemoselective Glycosylations
J . Org. Chem., Vol. 62, No. 23, 1997 8151
6H, Si(CH3)2); HR FAB-MS calcd for C46H66SO5SiNa 781.4298,
found 757.3890. Dicyclohexylmethyl 2,3,4-tri-O-benzyl-6-O-
(tert-butyldimethylsilyl)-1-thio-â-D-glucopyranoside (6â) was
obtained by the same synthetic procedure, starting from 5â,
as a colorless syrup: Rf 0.61 (CH2Cl2/petroleum ether (bp 40-
3H, H-5, H-6a, H-6b), 2.40-0.70 (m, 23H, SCH, 2 C6H11), 0.86
(s, 9H, SiC(CH3)3), 0.01 and 0.00 (2 s, 6H, Si(CH3)2).
Dicycloh exylm eth yl 2,3,4-Tr i-O-ben zoyl-1-th io-r-D-glu -
cop yr a n osid e (9r). A solution of 8R (1.38 g, 1.72 mmol) in
HOAc/H2O (9/1, v/v, 50 mL) was stirred for 16 h at 60 °C. The
solution was brought to rt, concentrated in vacuo, and co-
concentrated from toluene, MeOH, and CH2Cl2 (3 × 15 mL
each). Purification of the residue by silica gel column chro-
matography (toluene/acetone, 8/1, v/v) afforded 9R as a white
60 °C), 1/1, v/v); [R]25 +0.32° (c 1); 13C NMR (CDCl3) δ 138.8,
D
138.6, 138.0, and 128.4-127.6 (3 C6H5CH2), 85.7 (C-1), 82.7,
80.4, 77.6, and 72.1 (C-2,3,4,5), 75.9, 75.3, and 73.2 (3
C6H5CH2), 62.1 (C-6), 58.9 (SCH), 42.0, 40.0, and 32.3-26.6
(2 C6H11), 26.1 (SiC(CH3)3), 18.4 (SiC(CH3)3), -5.0 (Si(CH3)2);
1H NMR (CDCl3) δ 7.41-7.26 (m, 15H, 3 C6H5CH2), 5.27 (d,
1H, H-1, J 1,2 5.4 Hz), 4.98-4.66 (m, 6H, 3 C6H5CH2), 4.11-
3.59 (m, 6H, H-2, H-3, H-4, H-5, H-6a, H-6b), 2.40 (m, 1H,
SCH), 2.05-1.00 (m, 22H, 2 C6H11), 0.92 and 0.90 (2 s, 9H,
SiC(CH3)3), 0.05 and 0.04 (2 s, 6H, Si(CH3)2).
glass (893 mg, 76%): Rf 0.35 (toluene/acetone, 19/1, v/v); [R]25
D
+0.67° (c 1); FAB-MS: m/z 709 (M+ + Na); 13C NMR (CDCl3)
δ 166.6 and 165.7 (3 C6H5CO), 133.8-128.3 (3 C6H5CO), 86.2
(C-1), 71.8, 70.8, 70.5, and 69.6 (C-2, 3,4,5), 62.7 (SCH), 61.0
(C-6), 41.0, 39.6, and 32.1-26.2 (2 C6H11); 1H NMR (CDCl3) δ
8.10-7.20 (m, 15H, 3 C6H5CO), 6.05 (t, 1H, H-3, J 2,3J 3,4 10.0
Hz), 5.73 (d, 1H, H-1, J 1,2 5.8 Hz), 5.45 (dd, 1H, H-2), 5.49 (t,
1H, H-4, J 4,5 10.1 Hz), 4.48 (m, 1H, H-5), 3.76 (m, 2H, H-6a,
H-6b), 6.31 (m, 1H, SCH), 2.00-0.60 (m, 22H, 2 C6H11); HR
FAB-MS calcd for C40H46SO8Na 709.2811, found 709.2818.
Dicyclohexylmethyl 2,3,4-tri-O-benzoyl-1-thio-â-D-glucopyra-
noside (9â) was obtained by the same synthetic procedure,
starting from 8â, as a white solid: Rf 0.26 (toluene/acetone,
Dicycloh exylm eth yl 2,3,4-Tr i-O-ben zyl-1-th io-r-D-glu -
cop yr a n osid e (7r). A solution of 6R (1.35 g, 1.78 mmol) in
HOAc/H2O (9/1, v/v, 40 mL) was stirred for 18 h at 60 °C. The
solution was brought to rt, concentrated in vacuo, and co-
concentrated from toluene, MeOH, and CH2Cl2, respectively
(3 × 15 mL each). Purification of the residue by silica gel
column chromatography (CH2Cl2/acetone, 97/3, v/v) afforded
7R as a white glass (872 mg, 76%): Rf 0.33 (CH2Cl2/acetone,
19/1, v/v); [R]25 +0.18° (c 1); 13C NMR (CDCl3) δ 165.9 and
D
97/3, v/v); [R]25D +9.51° (c 1); FAB-MS m/z 667 (M+ + Na); 13
C
165.2 (3 C6H5CO), 133.7-128.4 (3 C6H5CO), 88.2 (C-1), 78.8,
74.2, 71.7, and 69.8 (C-2, 3,4,5), 63.1 (SCH), 62.1 (C-6), 40.8,
NMR (CDCl3), δ 138.8, 138.2, 137.9, and 128.6-127.6 (3
C6H5CH2), 86.1 (C-1), 82.6, 80.1, 77.2, and 71.5 (C-2,3,4,5), 75.7,
75.3, and 73.3 (3 C6H5CH2), 61.7 (C-6), 59.5 (SCH), 42.0, 39.7,
and 32.3-26.5 (2 C6H11); 1H NMR (CDCl3) δ 7.40-7.26 (m,
15H, 3 C6H5CH2), 5.24 (d, 1H, H-1, J 1,2 5.5 Hz), 5.01-4.64 (m,
6H, 3 C6H5CH2), 4.15 (m, 1H, H-5), 3.91-3.54 (m, 5H, H-2,
H-3, H-4, H-6a, H-6b), 2.46 (m, 1H, SCH), 2.05-1.00 (m, 22H,
2 C6H11); HR FAB-MS calcd for C40H52SO5Na 667.3433, found
667.3426. Dicyclohexylmethyl 2,3,4-tri-O-benzyl-1-thio-â-D-
glucopyranoside (7â) was obtained by the same synthetic
procedure, starting from 6â, as a colorless syrup: Rf 0.41 (CH2-
1
39.6, and 32.1-26.3 (2 C6H11); H NMR (CDCl3) δ 8.10-7.20
(m, 15H, 3 C6H5CO), 5.92 (t, 1H, H-3, J 2,3J 3,4 9.6 Hz), 5.53-
5.43 (m, 2H, H-2, H-4), 4.74 (d, 1H, H-1, J 1,2 9.9 Hz), 3.78 (m,
2 H, H-6a, H-6b), 2.43 (br s, 1H, OH), 2.32 (m, 1H, SCH), 2.10-
0.60 (m, 22H, 2 C6H11).
Dicycloh exylm et h yl 2,3,4-Tr i-O-b en zyl-6-O-(2,3,4,6-
tetr a -O-ben zyl-r-D-glu cop yr a n osyl)-1-th io-D-glu cop yr a -
n osid e (11). Meth od A. To a stirred mixture of ethyl 2,3,4,6-
tetra-O-benzyl-1-thio-â-D-glucopyranoside 10 (214 mg, 0.37
mmol), compound 7R (208 mg, 0.32 mmol), and molecular
sieves (4 Å, 2 g) in dry CH2Cl2/Et2O (1/5, v/v, 4 mL) was added
IDCP (354 mg, 0.76 mmol). After 1 h of stirring at rt, the
reaction mixture was decanted into a stirred and cooled (0 °C)
solution of aqueous Na2S2O3 (15%, w/v, 25 mL). After 1 h or
stirring, the mixture was diluted with CH2Cl2 (50 mL) and
transferred to a separatory funnel. The organic phase was
washed with aqueous Na2S2O3 (1 × 15 mL, 15%, w/v) and H2O
(2 × 15 mL), dried (MgSO4), filtered, and concentrated in
vacuo. Size exclusion column chromatography of the residue
(LH-20, CH2Cl2/MeOH, 1/1, v/v) afforded 11R as a colorless
Cl2/acetone, 97/3, v/v); [R]25 +1.06° (c 1); 13C NMR (CDCl3) δ
D
138.5, 138.1, 137.9, and 128.5-127.6 (3 C6H5CH2), 88.5 (C-1),
86.7, 82.7, 78.8, and 77.9 (C-2,3,4,5), 75.7, 75.7, and 75.0 (3
C6H5CH2), 62.5 (C-6), 61.6 (SCH), 41.3, 39.7, and 31.9-26.4
(2 C6H11); 1H NMR (CDCl3) δ 7.41-7.26 (m, 15H, 3 C6H5CH2),
5.03-4.57 (m, 6H, 3 C6H5CH2), 4.39 (d, 1H, H-1, J 1,2 9.9 Hz),
3.85 (m, 1H, H-5), 3.75-3.30 (m, 5H, H-2,3,4,6a,6b), 2.37 (m,
1H, SCH), 2.10-1.00 (m, 22H, 2 C6H11).
Dicycloh exylm eth yl 2,3,4-Tr i-O-ben zoyl-6-O-(ter t-bu -
tyld im eth ylsilyl)-1-th io-r-D-glu cop yr a n osid e (8r). To a
solution of 6R (1.20 g, 2.45 mmol) in dry pyridine (20 mL) was
added DMAP (40 mg, 0.33 mmol) and BzCl (1.3 mL, 11.2
mmol). After 18 h of stirring at rt, the mixture was diluted
with CH2Cl2 (60 mL) and washed with H2O (3 × 20 mL). The
organic layer was dried (MgSO4) and filtered. The filtrate was
concentrated in vacuo and co-concentrated from toluene,
MeOH, and CH2Cl2 (3 × 15 mL each). Purification of the
residue by silica gel column chromatography (CH2Cl2/petro-
leum ether (bp 40-60 °C), 3/1, v/v) afforded 8R as a white glass
(1.78 g, 91%): Rf 0.61 (CH2Cl2/petroleum ether (bp 40-60 °C),
syrup (139 mg, 40%): Rf 0.72 (CH2Cl2/acetone, 99/1, v/v); [R]25
D
+9.22° (c 1); FAB-MS m/z 1189 (M+ + Na); 13C NMR (CDCl3)
δ 138.8-127.5 (7 C6H5CH2), 97.5 (C-1′), 85.4 (C-1), 82.5 (C-3),
81.7 (C-3′), 80.1 (C-2/C-2′), 77.5 (C-4,4′), 71.2 (C-5), 70.4 (C-
5′), 68.3 (C-6′), 66.1 (C-6), 58.2(SCH), 42.0, 39.5, and 32.2-
26.4 (2 C6H11); 1H NMR (CDCl3) δ 7.40-7.10 (m, 35H, 7
C6H5CH2), 5.23 (d, 1H, H-1, J 1,2 5.5 Hz), 5.01 (d, 1H, H-1′, J 1′,2′
3.6 Hz), 5.00-4.42 (m, 14 H, 7 C6H5CH2), 4.24 (m, 1H, H-5),
3.96 (t, 1H, H-3′, J 2′,3′J 3,4′ 9.9 Hz), 3.95 (m, 1H, H-6a), 3.89 (t,
1H, H-3, J 2,3J 3,4 9.7 Hz), 3.84-3.55 (m, 2H, H-4, H-5′), 3.71-
3.64 (m, 4H, H-2, H-6b, H-4′, H-6′a), 3.64-3.54 (m, 3H, H-6b,
H-2′, H-4′, H-6′a), 3.64-3.54 (m, 3H, H-2′, H-4′, H-6′), 2.43 (m,
1H, SCH), 2.20-0.90 (m, 22 H, 2 C6H11); HR FAB-MS calcd
for C74H86SO10Na 1189.5839, found 1189.5827.
9/1, v/v); [R]25 +9.51° (c 1); FAB-MS m/z 823 (M+ + Na); 13C
D
NMR (CDCl3) δ 165.8 and 165.1 (3 C6H5CO), 133.3-128.3 (3
C6H5CO), 85.7 (C-1), 72.1, 71.3, 71.0, and 69.4 (C-2,3,4,5), 62.5
(C-6), 61.8 (SCH), 41.1, 39.7, and 32.1-26.6 (2 C6H11), 26.0
(SiC(CH3)3), 18.5 (SiC(CH3)3), -5.5 (Si(CH3)2); 1H NMR (CDCl3)
δ 8.10-7.20 (m, 15H, 3 C6H5CO), 5.94 (t, 1H, H-3, J 2,3 10.5,
J 3,4 9.8 Hz), 5.70 (d, 1H, H-1, J 1,2 5.7 Hz), 5.63 (t, 1H, H-4, J 4,5
9.8 Hz), 5.39 (dd, 1H, H-2), 4.53 (m, 1H, H-5), 3.9-3.7 (m, 2H,
H-6a, H-6b), 2.39 (m, 1H, SCH), 2.00-0.70 (m, 22H, 2 C6H11),
0.86 (s, 9H, SiC(CH3)3), -0.01 and -0.02 (2 s, 6H, Si(CH3)2);
HR FAB-MS calcd for C46H60SO8SiNa 823.3676, found 823.3657.
Dicyclohexylmethyl 2,3,4-tri-O-benzoyl-6-O-(tert-butyldimeth-
ylsilyl)-1-thio-â-D-glucopyranoside (8â) was obtained by the
same synthetic procedure, starting from 6â, as a white glass:
Meth od B. To a stirred mixture of ethyl 2,3,4,6-tetra-O-
benzyl-1-thio-â-D-glucopyranoside 10 (121 mg, 0.21 mmol),
compound 7â (105 mg, 0.16 mmol), and powdered molecular
sieves (4 Å, 0.5 g) in dry CH2Cl2/Et2O (1/5, v/v, 3 mL) was
added IDCP (226 mg, 0.48 mmol). After 2 h of stirring at rt,
the reaction mixture was filtered, diluted with CH2Cl2 (75 mL),
and transferred to a separatory funnel. The organic phase was
washed with aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O
(2 × 20 mL), dried (MgSO4), filtered, and concentrated in
vacuo. Size exclusion column chromatography of the residue
(LH-20, CH2Cl2/MeOH, 1/1, v/v) afforded 11â as a colorless
syrup (133 mg, 71%).
Meth od C. To a stirred mixture of compound 3R (79 mg,
0.11 mmol), compound 7â (62 mg, 0.10 mmol), and molecular
sieves (4 Å, 0.5 g) in dry CH2Cl2/Et2O (1/5, v/v, 3 mL) was
added IDCP (60 mg, 0.13 mmol). After 2 h of stirring at rt,
the reaction mixture was quenched with aqueous Na2S2O3 (3
mL, 15%, w/v), transferred to a separatory funnel, and diluted
Rf 0.53 (CH2Cl2/petroleum ether (bp 40-60 °C), 9/1, v/v); [R]25
D
-3.58° (c 1); 13C NMR (CDCl3) δ 165.8 and 165.1 (3 C6H5CO),
133.3-128.2 (3 C6H5CO), 87.5 (C-1), 79.4, 74.7, 71.9, and 69.7
(C-2,3,4,5), 62.9 (C-6), 61.8 (SCH), 40.8, 39.6, and 32.2-26.2
(2 C6H11), 26.0 (SiC(CH3)3), 18.3 (SiC(CH3)3), -5.5 (Si(CH3)2);
1H NMR (CDCl3) δ 8.10-7.25 (m, 15H, 3 C6H5CO), 5.84 (t, 1H,
H-3, J 2,3J 3,4 9.6 Hz), 5.55 (dd, 1H, H-2, J 1,2 9.9 J 2,3 9.6 Hz),
5.45 (t, 1H, H-4, J 4,5 9.6 Hz), 4.71 (d, 1H, H-1), 3.85-3.75 (m,

8152 J . Org. Chem., Vol. 62, No. 23, 1997
Geurtsen et al.
with CH2Cl2 (50 mL). The organic phase was washed with
aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O (1 × 15 mL),
dried (MgSO4), filtered, and concentrated in vacuo. Silica gel
column chromatography (CH2Cl2/acetone, 996/4, v/v) of the
residue afforded 11â as a colorless syrup (63 mg, 50%): Rf 0.76
Cl2/acetone, 98/2, v/v); [R]25 +5.24° (c 1), FAB-MS m/z 1287
D
(M+ + Na); 13C NMR (CDCl3) 166.1, 165.7, and 165.1 (7
C6H5CO), 133.5-128.3 (7 C6H5CO), 101.1 (C-1), 87.5 (C-1′),
78.6, 74.2, 72.9, 72.2, 71.5, 69.8, and 69.6 (C-2,3,4,5,2′,3′,4′,5′),
68.4 and 63.1 (C-6,6′), 61.7 (SCH), 41.0, 40.0, and 31.6-26.1
(2 C6H11); 1H NMR (CDCl3) δ 8.07-7.22 (m, 35H, 7 C6H5CO),
5.87 (t, 1H, H-3, J 2,3J 3,4 9.5 Hz), 5.77 (t, 1H, H-3′, J 2′,3′J 3′,4′ 9.5
Hz), 5.58 (t, 1H, H-4, J 4,5 9.5 Hz), 5.45 (dd, 1H, H-2, J 1,2 7.9
Hz), 5.39 (dd, 1H, H-2′, J 1′,2′ 10.0, J 2′,3′9.5 Hz), 5.33 (t, 1H, H-4′),
5.06 (d, 1H, H-1), 4.64 (d, 1H, H-1′), 4.60 (dd, 1H, H-6a, J 5,6a
3.1, J 6a,6b -12.0 Hz), 4.43 (dd, 1H, H-6b, J 5,6b 5.1 Hz), 4.09 (m,
1H, H-5), 4.03-3.91 (m, 3H, H-5′, H-6′a, H-6′b), 2.29 (m, 1H,
SCH), 2.07-0.60 (m, 22H, 2 C6H11); HR FAB-MS calcd for
C74H72SO17Na 1287.4388, found 1287.4400.
(CH2Cl2/acetone, 98/2, v/v); [R]25 +3.26° (c 1); 13C NMR
D
(CDCl3) δ 138.9-127.6 (7 C6H5CH2), 97.5 (C-1′), 88.1 (C-1), 86.8
(C-3′), 82.7 (C-2′), 81.8 (C-3), 80.2 (C-2), 79.0 (C-5′), 77.7 (C-
4), 77.4 (C-5/C-4), 75.7, 75.6, 75.0, 73.5, and 71.8 (7 C6H5CH2),
70.5 (C-5/C-4′), 68.8 (C-6), 66.1 (C-6′), 60.3 (SCH), 41.4, 39.5,
and 32.0-26.6 (2 C6H11); 1H NMR (CDCl3) δ 7.45-7.15 (m,
35H, 7 C6H5CH2), 5.20 (d, 1H, H-1′, J 1,2 3.5 Hz), 4.99-4.46
(m, 14H, 7 C6H5CH2), 4.34 (m, 1H, H-1, J 1′,2′ 9.7 Hz), 3.97 (t,
1H, H-3′, J 2′,3′J 3′,4′ 8.9 Hz), 3.88 (dd, 1H, H-6′a, J 5′,6′a 3.5 Hz,
J 6′a,6′b -12.5 Hz), 3.81-3.76 (m, 3H, H-5, H-4′, H-6′b), 3.70 (dd,
1H, H-6a, J 5,6a 3.8, J 6a,6b -10.8 Hz), 3.65-3.56 (m, 4H, H-2,
H-4, H-6b, H-3′), 3.32 (m, 1H, H-5′), 3.11 (dd, 1H, H-2′), 2.37
(m, 1H, CHS), 1.97 and 1.80-1.00 (m, 22H, 2 C6H11).
Meth od B. To a stirred mixture of ethyl tetra-O-benzoyl-
1-thio-â-D-glucopyranoside 16 (111 mg, 0.17 mmol), compound
9â (109 mg, 0.16 mmol), and molecular sieves (4 Å, 1.0 g) in
dry CH2Cl2/ Et2O (1/1, v/v, 1 mL) were added NIS (38 mg, 0.17
mmol) and TMSOTf (6 µL, 0.03 mmol). After 10 min of stirring
at rt, the reaction mixture was quenched with TEA (0.02 mL),
diluted with CH2Cl2 (60 mL), and washed with aqueous
Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O (2 × 15 mL). The
organic layer was dried (MgSO4) and filtered, and the filtrate
was concentrated in vacuo. Purification of the residue by size
exclusion column chromatography (LH-20, CH2Cl2/MeOH, 1/1,
v/v) afforded 17â as a white glass (108 mg, 41%): Rf 0.64 (CH2-
E t h yl 2,3,4-Tr i-O-b en zoyl-6-O-(2,3,4-t r i-O-b en zyl-6-O-
(2,3,4,6-tetr a-O-ben zyl-r-D-glu copyr an osyl)-r/â-D-glu copy-
r a n osyl)-1-th io-â-D-glu cop yr a n osid e (13). Meth od A. To
a stirred mixture of ethyl 2,3,4-tri-O-benzoyl-â-D-glucopyra-
noside 12 (158 mg, 0.14 mmol), compound 11R (83 mg, 0.16
mmol), and molecular sieves (4 Å, 0.5 g) in CH2Cl2/ Et2O (1/5,
v/v, 2 mL) were added NIS (38 mg, 0.17 mmol) and TfOH (5
µL, 0.06 mmol). After 5 min of stirring at rt, the reaction
mixture was neutralized with TEA (0.02 mL), diluted with
CH2Cl2 (50 mL), and washed with aqueous Na2S2O3 (2 × 15
mL, 15%, w/v) and H2O (2 × 15 mL). The organic phase was
dried (MgSO4) and filtered. The filtrate was concentrated in
vacuo. Size exclusion chromatography of the residue (LH-20,
CH2Cl2/MeOH, 1/1, v/v) afforded 13 as a white glass (142 mg,
69%): Rf 0.36 (CH2Cl2/acetone, 98/2, v/v); FAB-MS m/z 1491
(M+ + Na); 13C NMR (CDCl3) δ 165.9 and 165.2 (3 C6H5CO),
139.0, 138.6, 138.4, 138.1, and 133.5-127.6 (3 C6H5CO, 7 C6H5-
CH2), 97.3 and 97.0 (C-1,1′,1′′), 83.7, 81.9, 81.7, 80.4, 80.0, 77.4,
74.4, 70.8, 70.3, and 69.8 (C-2,3,4,5,2′,3′,4′,5′,2′′,3′′,4′′,5′′), 75.6,
75.0, 74.8, 73.5, 73.3, and 72.0 (7 C6H5CH2), 68.5, 66.8, and
65.6 (C-6,6′,6′′), 24.4 (SCH2CH3), 14.9 (SCH2CH3); 1H NMR
(CDCl3) δ 7.89-7.04 (m, 50 H, 3 C6H5CO, 7 C6H5CH2, 5.79 (t,
1H, H-3, J 2,3J 4,5 10.0 Hz), 5.42 (t, 1H, H-4, J 3,4J 4,5 10.0 Hz),
5.40 (t, 1H, H-2, J 1,2 10.0 Hz), 4.92 (d, 1H, H-1′, J 1′,2′ 3.6 Hz),
4.89-4.33 (m, 14H, 7 C6H5CH2), 4.68 (d, 1H, H-1, J 1,2 10.0 Hz),
4.59 (d, 1H, H-1′′, J 1′′,2′′ 3.6 Hz), 3.95 (m, 1H, H-5, J 4,5 10.0,
J 5,6a 2.0, J 5,6b 7.0 Hz), 2.89 (t, 1H, H-3′′, J 2′′,3′′J 3′′,4′′ 9.8 Hz), 3.88
(dd, 1H, H-3′, J 2′,3′ 9.7, J 3′,4′ 9.0 Hz), 3.81-3.42 (m, 10H, H-6a,
H-6b, H-4′, H-5′, H-6′a, H-6′b, H-4′′, H-5′′, H-6′′a, H-6′′b), 3.45
(dd, 1H, H-2′, J 2′,3′ 9.7 Hz), 3.32 (dd, 1H, H-2′′, J 1′′,2′′ 3.6, J 2′′,3′′
9.8 Hz), 2.70-2.55 (m, 2H, SCH2CH3), 1.10 (t, 3H, SCH2CH3,
J 7.2 Hz); HR FAB-MS calcd for C90H90SO18Na 1513.5746,
found 1513.5836.
Meth od B. To a stirred mixture of ethyl 2,3,4-tri-O-
benzoyl-â-D-glucopyranoside 12 (323 mg, 0.28 mmol), com-
pound 11â (180 mg, 0.34 mmol), and molecular sieves (4 Å,
0.6 g) in dry CH2Cl2/H2O (1/1, v/v, 6 mL) were added NIS (75
mg, 0.33 mmol) and TMSOTf (5 µL, 0.03 mmol). After 30 min
of stirring at rt, the reaction mixture was neutralized with
TEA (0.02 mL), diluted with CH2Cl2 (50 mL), and washed with
aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O (2 × 15 mL).
The organic phase was dried (MgSO4) and filtered. The filtrate
was concentrated in vacuo. Size exclusion column chroma-
tography of the residue (LH-20, CH2Cl2/MeOH, 1/1, v/v)
afforded 13 as a white glass (125 mg, 30%).
Dicycloh exylm et h yl 2,3,4-Tr i-O-b en zoyl-6-O-(2,3,4,6-
tetr a -O-ben zoyl-â-D-glu cop yr a n osyl)-1-th io-D-glu cop yr a -
n osid e (17). Meth od A. To a stirred mixture of ethyl tetra-
O-benzoyl-1-thio-â-D-glucopyranoside 16 (99 mg, 0.15 mmol),
compound 9R (97 mg, 0.14 mmol), and molecular sieves (4 Å,
1.0 g) in dry CH2Cl2/ Et2O (1/1, v/v, 1 mL) were added NIS (33
mg, 0.15 mmol) and TMSOTf (6 µL, 0.03 mmol). After 5 min
of stirring at rt, the reaction mixture was quenched with TEA
(0.02 mL), diluted with CH2Cl2 (60 mL), and washed with
aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O (2 × 15 mL).
The organic layer was dried (MgSO4) and filtered, and the
filtrate was concentrated in vacuo. Purification of the residue
by size exclusion chromatography (LH-20, CH2Cl2/MeOH, 1/1,
v/v) afforded 17R as a white glass (115 mg, 64%): Rf 0.67 (CH2-
Cl2/acetone, 98/2, v/v); [R]25 +0.06° (c 1); 13C NMR (CDCl3) δ
D
166.1, 165.8, 165.4, and 165.1 (7 C6H5CO), 133.2-128.3 (7
C6H5CH2), 101.4 (C-1), 85.5 (C-1′), 73.0 (C-3/C-3′), 72.3 (C-5′),
71.7 (C-2, 2′), 70.7 (C-3/C-3′), 69.7 (C-4′), 69.3 (C-4), 69.0 (C-
5), 67.7 (C-6), 63.1 (C-6′), 61.4 (SCH), 41.0, 39.4, and 32.0-
26.1 (2 C6H11); 1H NMR (CDCl3) δ 8.20-7.20 (m, 35H, 7
C6H5CO), 5.91 (t, 2H, H-3 and H-3′ overlapping), 5.621 (t, 1H,
H-4′, J 3′,4′J 4′,5′ 9.7 Hz), 5.615 (d, 1H, H-1, J 1,2 5.6 Hz), 5.55 (dd,
1H, H-2′, J 1′,2′ 7.8, J 2′,3′ 9.7 Hz), 5.45 (t, 1H, H-4, J 3,4J 4,5 9.7
Hz), 5.18 (dd, 1H, H-2, J 2,3 10.5 Hz), 4.93 (d, 1H, H-1′), 4.65
(m, 1H, H-5, J 5,6a 2.5, J 5,6b 4.0 Hz), 4.55 (dd, 1H, H-6′a, J 5′,6′a
3.4, J 6′a,6′b -12.1 Hz), 4.45 (dd, 1H, H-6′b, J 6a,6b -10.9 Hz), 4.18
(dd, 1H, H-6a), 4.10 (m, 1H, H-5′, J 5′,6′b 5.0 Hz), 3.77 (dd, 1H,
H-6b), 2.29 (m, 1H, SCH), 1.90-0.70 (m, 2 C6H11).
Meth yl 2,3,4-Tr i-O-ben zyl-6-O-(2,3,4-tr i-O-ben zoyl-6-O-
(2,3,4,6-tetr a -O-ben zoyl-â-D-glu cop yr a n osyl)-â-D-glu cop y-
r an osyl)-r-D-glu copyr an oside (18). Meth od A. To a stirred
mixture of compound 17R (124 mg, 0.27 mmol), methyl 2,3,4-
tri-O-benzyl-R-D-glucopyranoside 14 (253 mg, 0.20 mmol), and
molecular sieves (4 Å, 0.7 g) in dry CH2Cl2 (10 mL) were added
NIS (249 mg, 1.11 mmol) and TMSOTf (30 µL, 0.17 mmol).
After 30 min of stirring at rt, the reaction mixture was
quenched with TEA (0.04 mL), diluted with CH2Cl2 (60 mL),
and washed with aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and
H2O (2 × 15 mL). The organic layer was dried (MgSO4) and
filtered, and the filtrate was concentrated in vacuo. Purifica-
tion of the residue by silica gel column chromatography (CH2-
Cl2/acetone, 99/1, v/v) afforded 18 as a white glass (220 mg,
73%).
Meth od B. To a stirred mixture of compound 17â (181 mg,
0.14 mmol), methyl 2,3,4-tri-O-benzyl-R-D-glucopyranoside 14
(80 mg, 0.17 mmol), and molecular sieves (4 Å, 2.0 g) in dry
CH2Cl2/ Et2O (5 mL, 1/1, v/v) were added NIS (133 mg, 0.60
mmol) and TMSOTf (21 µL, 0.12 mmol). After 10 min of
stirring at rt, the reaction mixture was quenched with TEA
(0.04 mL), diluted with CH2Cl2 (60 mL), and washed with
aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O (2 × 15 mL).
The organic layer was dried (MgSO4) and filtered, and the
filtrate was concentrated in vacuo. Purification of the residue
by silica gel column chromatography (CH2Cl2/acetone, 99/1,
v/v) afforded 18 as a white glass (159 mg, 73%): Rf 0.32 (CH2-
Cl2/acetone, 98/2, v/v); [R]25 +1.65° (c 1); FAB-MS m/z 1539
D
(M+ + Na); 13C NMR (CDCl3) 166.1, 165.7, 165.4, 165.14,
165.08, and 164.8 (7 C6H5CO), 138.9, 138.4, 138.2, 133.5, 133.4,
133.2, 133.2, and 129.8-127.3 (7 C6H5CO, 3 C6H5CH2), 101.4
(C-1), 100.7 (C-1′), 98.2 (C-1′′), 81.9, 79.7, 77.0, 75.5, 74.5, 74.4,
73.5, 72.7, 72.3, 72.0, and 71.8 (C-2,3,4,5,2′,3′,4′,5′,2′′,3′′,4′′,5′′),
69.6, 69.5, and 69.4 (3 C6H5CH2), 68.5, 67.5, and 63.0 (C-
6,6′,6′′), 55.4 (OCH3); 1H NMR (CDCl3) δ 8.10-6.90 (m 50H, 7
C6H5CO, 3 C6H5CH2), 5.84 (t, 1H, H-3′′, J 2′′,3′′J 3′′,4′′ 10.0 Hz),
5.75 (t, 1H, H-3′, J 2′,3′J 3′,4′ 10.0 Hz), 5.61 (t, 1H, H-4′′, J 4′′,5′′ 9.8

Chemoselective Glycosylations
J . Org. Chem., Vol. 62, No. 23, 1997 8153
Hz), 5.49 (t, 1H, H-2′′, J 1′′,2′′ 8.0 Hz), 5.46 (t, 1H, H-2′, J 1′,2′ 7.9
Hz), 5.30 (t, 1H, H-4′, J 4′,5′ 9.8 Hz), 4.99 (d, 1H, H-1′′), 4.59
(dd, 1H, H-6′′a, J 6′′a,6′′b -12.0 Hz), 4.58 (d, 1H, H-1, J 1,2 2.8
Hz), 4.50 (d, 1H, H-1′), 4.41 (dd, 1H, H-6b′′, J 5′′,6′′b 5.6 Hz), 4.07
(m, 1H, H-5′′), 4.02 (m, 1H, H-6′a), 3.93-3.87 (m, 2H, H5′,
H6′b), 3.85 (t, 1H, H-3, J 2,3J 3,4 9.2 Hz), 3.50 (m, 1H, H-5), 3.44-
3.35 (m, 4H, H-2, H-4, H-6a, H-6b), 3.34 (s, 3H, OCH3); HR
FAB-MS calcd for C89H80O23Na 1539.4988, found 1539.4951.
H-6b), 2.36 (d, 1H, OH, J 4,OH 2.0 Hz), 2.44-1.00 (m, 23H, SCH,
2 C6H11); HR FAB-MS calcd for C40H52SO5Na 667.3433, found
667.3422.
Dicycloh exylm et h yl 2,3-Di-O-b en zoyl-6-O-b en zyl-1-
th io-r-D-glu cop yr a n osid e (24). To a stirred mixture of
compound 22 (5.6 g, 8.4 mmol) and molecular sieves (4 Å, 10
g) in dry THF (80 mL) was added NaCNBH4 (5.9 g, 94.0 mmol).
After 30 min of stirring at rt, a solution of HCl in dry Et2O
was added dropwise (50 mL, 1.0 M). The mixture was filtered
over Celite, diluted with Et2O (100 mL), and washed with H2O
(2 × 40 mL), aqueous NaHCO3 (4 × 40 mL, 10%, w/v), and
H2O (2 × 40 mL). The organic phase was dried (MgSO4),
filtered, and concentrated. Purification of the residue by silica
gel column chromatography (CH2Cl2) afforded 24 as a white
Dicycloh exylm eth yl 2,3-Di-O-ben zyl-4,6-O-ben zyliden e-
1-th io-r-D-glu cop yr a n osid e (21). To a solution of 2R (2.6
g, 7.0 mmol) in dry DMF (30 mL) were added benzaldehyde
dimethyl acetal (1.3 mL, 8.7 mmol) and camphorsulfonic acid
(70 mg, 0.3 mmol). The solution was stirred for 3 h at 57 °C
under reduced pressure (20 mmHg). The reaction mixture was
diluted with Et2O (100 mL) and washed with aqueous 1 M
NaHCO3 (1 × 20 mL) and H2O (1 × 20 mL). The organic phase
was dried (MgSO4), filtered, concentrated in vacuo, and co-
concentrated from toluene. Purification of the residue by silica
gel column chromatography (toluene/EtOAc, 7/3, v/v) afforded
20 as a white glass (3.2 g, 100%). Compound 20 (1.36 g, 2.94
mmol) was dissolved in dry DMF (15 mL); NaH (282 mg, 11.8
mmol) and BnBr (1.0 mL, 8.8 mmol) were added, and the
mixture was stirred for 2.5 h at rt, diluted with EtOAc (175
mL), and washed with H2O (2 × 25 mL). The organic phase
was dried (MgSO4), filtered, concentrated in vacuo, and co-
concentrated from toluene (3 × 30 mL), MeOH (3 × 20 mL),
and CH2Cl2 (3 × 20 mL), respectively. Purification of the
residue by silica gel column chromatography (CH2Cl2/petro-
leum ether (bp 40-60 °C), 3/1, v/v) afforded 21 as a white solid
(1.76 g, 93%): Rf 0.36 (CH2Cl2/petroleum ether (bp 40-60 °C),
glass (4.28 g, 76%): Rf 0.68 (CH2Cl2/acetone, 99/1, v/v); [R]25
D
+2.56° (c 1); FAB-MS m/z 695 (M+ + Na); 13C NMR (CDCl3) δ
167.0 and 165.9 (2 C6H5CO), 137.8 and 133.4-127.7 (2 C6H5-
CO, C6H5CH2), 85.9 (C-1), 74.3, 71.3, 70.9, and 70.6 (C-2,3,4,5),
73.8 (C6H5CH2), 69.3 (C-6), 62.0 (SCH), 41.0 and 40.0 (2 C6H11),
1
41.0, 40.0, and 32.1-26.1 (2 C6H11); H NMR (CDCl3) δ 8.1-
7.2 (m, 15H, 2 C6H5CO and C6H5CH2), 5.61 (d, 1H, H-1, J 1,2
5.7 Hz), 5.60 (t, 1H, H-3, J 2,3 9.6, J 3,4 9.6 Hz), 5.40 (dd, 1H,
H-2), 4.68 and 4.58 (2 d, 2H, C6H5CH2, J 12.1 Hz), 4.43 (m,
1H, H-5), 4.02 (dt, 1H, H-4, J 4,OH 4.0, J 4,5 9.6 Hz), 3.89 (dd,
1H, H-6a, J 5,6a 3.7, J 6a,6b -10.3 Hz), 3.74 (dd, 1H, H-6b, J 5,6b
3.7 Hz), 2.98 (d, 1H, OH), 2.33 (t, 1H, SCH, J 5.9 Hz), 1.9-0.6
(m, 22H, 2 C6H11); HR FAB-MS calcd for C40H48SO7Na
695.3018, found 695.3003.
Dicycloh exylm et h yl 2,3,6-Tr i-O-b en zyl-6-O-(2,3,4,6-
t et r a -O-b en zyl-r-D-glu cop yr a n osyl)-1-t h io-r-D-glu cop y-
r a n osid e (25). To a stirred mixture of compound 10 (135 mg,
0.23 mmol), compound 23 (110 mg, 0.16 mmol), and molecular
sieves (4 Å, 3 g) in dry CH2Cl2/Et2O (1/5, v/v, 5 mL) was added
IDCP (220 mg, 0.47 mmol). After 1.5 h of stirring at rt, the
reaction mixture was decanted into a stirred and cooled (0 °C)
solution of aqueous Na2S2O3 (15%, w/v, 25 mL). After 2 h of
stirring, the mixture was diluted with CH2Cl2 (50 mL) and
transferred to a seporatory funnel. The organic phase was
washed with aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O
(1 × 15 mL), dried (MgSO4), filtered, and concentrated in
vacuo. Purification of the residue by size exclusion column
chromatography (LH-20, CH2Cl2/MeOH, 1/1, v/v) afforded 25R
as a colorless syrup (77 mg, 31%): Rf 0.72 (CH2Cl2/acetone,
3/1, v/v); [R]25 +8.88° (c 1); FAB-MS m/z 665 (M + Na)+; 13C
D
NMR (CDCl3) δ 138.9, 138.0, 137.5, and 129.0-126.1 (3 C6H5-
CH2), 101.3 (C6H5CH), 87.5, 82.1, 79.5, 79.4, and 63.3 (C-
1,2,3,4,5), 75.4 and 73.3 (2 C6H5CH2), 68.9 (C-6), 59.8 (SCH),
41.9-26.6 (2 C6H11); 1H NMR (CDCl3) δ 7.56-7.26 (m, 15H, 3
C6H5CH2), 5.59 (C6H5CH), 5.26 (d, 1H, H-1, J 1,2 5.6 Hz), 4.96-
4.68 (m, 4H, 2 C6H5CH2), 4.42-3.61 (m, 6H, H-2, H-3, H-4,
H-5, H-6a, H-6b), 2.39-1.05 (m, 23H, SCH, 2 C6H11); HR FAB-
MS calcd for C40H50SO5Na 665.3277, found 665.3283.
Dicycloh exylm et h yl 2,3-Di-O-b en zoyl-4,6-O-b en zyli-
d en e-1-th io-r-D-glu cop yr a n osid e (22). To a solution of 20
(1.54 g, 3.33 mmol) in dry pyridine (15 mL) were added BzCl
(1.2 mL, 10.3 mmol) and DMAP (81 mg, 0.66 mmol). After 18
h of stirring at rt, the reaction mixture was diluted with EtOAc
(50 mL) and washed with H2O (3 × 15 mL). The organic phase
was dried (MgSO4), filtered, and concentrated in vacuo.
Purification of the residue by silica gel column chromatography
(petroleum ether (bp 40-60 °C), 1/1, v/v) afforded 22 as a white
solid (2.06 g, 92%): Rf 0.38 (CH2Cl2/petroleum ether (bp 40-
99/1, v/v); [R]25 +8.33° (c 1); FAB-MS m/z 1190 (M+ + Na);
D
13C NMR (CDCl3) δ 138.9-138.0 and 128.3-126.4 (7 C6H5CH2),
96.7 (C-1′), 86.1 (C-1), 82.6, 81.9, 80.2, 79.6, 77.7, 72.2, 70.9,
and 70.5 (C-2,3,4,5,2′,3′,4′,5′), 75.5-73.1 (7 C6H5CH2), 68.9 and
68.2 (C-6,6′), 59.9 (SCH), 39.9 and 29.7-26.3 (2 C6H11); 1H
NMR (CDCl3) δ 7.30-7.00 (m, 35H, 7 C6H5CH2), 5.65 (d, 1H,
H-1′, J 1,2 2.3 Hz), 5.24 (d, 1H, H-1, J 1′,2′ 3.3 Hz), 4.99-4.16 (7
C6H5CH2), 4.26 (m, 1H, H-5′), 4.01 (dd, 1H, H-4′, J 3′,4′J 4′,5′ 7.4
Hz), 3.90-3.81 (m, 3H, H-3, H-6a, H-3′), 3.77 (dd, 1H, H-2′,
J 1′,2′ 4.1, J 2′,3′ 7.4 Hz), 3.70 (m, 1H, H-5), 3.59 (dd, 1H, H-4, J 3,4
6.7, J 4,5 7.4 Hz), 3.51 (dd, 1H, H-6b, J 5,6b 1.5, J 6a,6b -8.1 Hz),
3.42 (dd, 1H, H-2, J 1,2 2.7, J 2,3 7.3 Hz), 3.40 (dd, 1H, H-6′a,
J 5′,6′a 2.0, J 6′a,6′b -8.3 Hz), 3.31 (dd, 1H, H-6′b, J 5′,6′b 1.3 Hz),
2.4 (m, 1H, SCH), 2.0-0.9 (m, 22H, 2 C6H11); HR FAB-MS
calcd for C74H86SO10Na 1189.5839, found 1189.5817.
60 °C), 1/1, v/v); [R]25 +1.59° (c 1); FAB-MS m/z 693 (M+
+
D
Na); 13C NMR (CDCl3) δ 165.8, 165.4 (2 C6H5CO), 136.8 and
133.3-126.0 (2 C6H5CO), 101.4 (C6H5CH), 86.8 (C-1), 79.3,
72.2, 69.8, and 63.4 (C-2,3,4,5), 68.6 (C-6), 62.1 (SCH), 40.9,
1
39.3, and 31.9-26.1 (2 C6H11); H NMR (CDCl3) δ 8.10-7.20
(m, 10H, 2 C6H5CO), 5.91 (t, 1H, H-3, J 2,3J 3,4 10.3 Hz), 5.64
(d, 1H, H-1, J 1,2 5.9 Hz), 5.59 (s, 1H, C6H5CH), 5.42 (t, 1H,
H-2), 4.56 (m, 1H, H-5), 4.30 (dd, 1H, H-4, J 4,5 4.8 Hz), 3.90
(m, 2H, H-6a, H-6b), 2.30 (m, 1H, SCH), 2.0-0.6 (2 C6H11);
HR FAB-MS calcd for C40H46SO7Na 693.2862, found 693.2860.
Eth yl 2,3,6-Tr i-O-ben zoyl-4-O-(2,3,4,6-tetr a -O-ben zyl-
r-D-glu cop yr a n osyl)-1-th io-â-D-glu cop yr a n osid e (27). To
a stirred mixture of ethyl 2,3,6-tri-O-benzoyl-1-thio-â-D-glu-
copyranoside 26 (101 mg, 0.19 mmol), compound 3R (132 mg,
0.18 mmol), and molecular sieves (4 Å, 0.3 g) in dry CH2Cl2/
Et2O (1/1, v/v, 4 mL) were added NIS (46 mg, 0.20 mmol) and
TfOH (5.5 µL, 0.06 mmol). After 5 min of stirring at rt, the
reaction mixture was quenched with TEA (0.02 mL), diluted
with CH2Cl2 (60 mL), transferred to a separatory funnel, and
washed with aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O
(2 × 15 mL). The organic phase was collected, dried (MgSO4),
filtered, and concentrated in vacuo. Purification of the residue
by size exclusion column chromatography (LH-20, CH2Cl2/
MeOH, 1/1) afforded 27 as a white glass (116 mg, 61%): Rf
0.44 (CH2Cl2/acetone, 98/2, v/v); CI-MS m/z 1076 (M+ + NH4);
13C NMR (CDCl3) δ 165.9, 165.6, and 165.5 (3 C6H5CO), 138.7,
138.4, 138.1, 137.9, 133.3, 133.1, 133.0, and 130.0-127.6 (4
C6H5CH2, 3 C6H5CO), 99.9 (C-1′), 83.6 (C-1), 81.3 (C-3′), 78.9
(C-2′), 77.6 (C-5), 77.2 (C-4′), 76.8 (C-4), 75.3 (C-3), 71.8 (C-
Dicycloh exylm eth yl 2,3,6-Tr i-O-ben zyl-1-th io-r-D-glu -
cop yr a n osid e (23). To a stirred and cooled (0 °C) solution
of 21 (1.63 g, 2.54 mmol) and triethylsilane (2.0 mL, 12.5
mmol) in CH2Cl2 (20 mL) was added TFA (1.0 mL, 13.0 mmol).
The solution was stirred for 15 min, diluted with CH2Cl2 (60
mL), transferred to a separating funnel, and washed with
aqueous NaHCO3 (2 × 15 mL, 10%, w/v) and H2O (2 × 15 mL).
The organic phase was dried (MgSO4), filtered, and concen-
trated in vacuo. Purification of the residue by silica gel column
chromatography (CH2Cl2/acetone 98/2, v/v, 1/1) afforded 23 as
a white solid (1.4 g, 85%): Rf 0.54 (CH2Cl2/acetone, 96/4, v/v);
[R]25 +8.02° (c 1); FAB-MS m/z 667 (M+ + Na); 13C NMR
D
(CDCl3) δ 138.9, 138.2, 137.9, and 128.6-127.7 (3 C6H5CH2),
86.1 (C-1), 82.1, 79.6 and 70.7 (C-2,3,4,5), 75.5, 73.7, and 73.0
(3 C6H5CH2), 69.4 (C-6), 59.1 (SCH), 41.9, 39.8, and 38.5-26.4
(2 C6H11); 1H NMR (CDCl3) δ 7.45-7.22 (m, 15 H, 3 C6H5CH2),
5.31 (d, 1H, H-1, J 1,2 5.8 Hz), 5.03-4.88 (m, 6H, 3 C6H5CH2),
4.22 (m, 1H, H-5), 3.81-3.57 (m, 5H, H-2, H-3, H-4, H-6a,

8154 J . Org. Chem., Vol. 62, No. 23, 1997
Geurtsen et al.
5′), 70.8 (C-2), 68.5 (C-6′), 63.8 (C-6), 24.3 (SCH2CH3), and 14.9
(SCH2CH3); 1H NMR (CDCl3) δ 8.20-7.10 (4 C6H5CH2, 3 C6H5-
CO), 5.94 (t, 1H, H-3, J 2,3J 3,4 9.2 Hz), 5.60 (t, 1H, H-2, J 1,2 9.2
Hz), 4.96 (m, 1H, H-6a, J 6a,6b -12.2 Hz), 4.95 (m, 1H, H-1′,
J 1′,2′ 3.0 Hz), 4.82 (d, 1H, H-1), 4.67 (m, 1H, H-6b), 4.25 (t, 1H,
H-4, J 4,5 9.0 Hz), 3.99 (m, 1H, H-5, J 5,6a 2.0, J 5,6b 4.6 Hz), 3.98
(m, 1H, H-3′), 3.94 (m, 1H, H-5′), 3.62 (m, 2H, H-6a′, H-6b′,
J 6a,6b -12.2 Hz), 3.60 (m, 1H, H-4′), 3.31 (dd, 1H, H-2′), 2.77
(m, 2H, SCH2CH3), 1.27 (m, 3H, SCH2CH3). Anal. Calcd for
C63H62SO13: C, 71.48; H, 5.90. Found: C, 71.05; H, 6.07.
Dicycloh exylm eth yl 2,3-Di-O-ben zoyl-6-O-ben zyl-4-O-
(2-O-a cetyl-3,4,6-tr i-O-ben zyl-â-D-glu cop yr a n osyl)-1-th io-
r-D-glu cop yr a n osid e (30). To a stirred mixture of ethyl 2-O-
acetyl-3,4,6-tri-O-benzyl-1-thio-â-D-glucopyranoside 28 (89 mg,
0.17 mmol), compound 24 (101 mg, 0.15 mmol), and molecular
sieves (4 Å, 1 g) in dry CH2Cl2/Et2O (1/1, v/v, 4 mL) were added
NIS (41 mg, 0.18 mmol) and TfOH (5 µL, 0.03 mmol). After
10 min of stirring at rt, the reaction mixture was quenched
with TEA (20 µL), diluted with CH2Cl2 (60 mL), transferred
to a separatory funnel, and washed with aqueous Na2S2O3 (2
× 15 mL, 15%, w/v) and H2O (2 × 15 mL). The organic phase
was collected, dried (MgSO4), filtered, and concentrated in
vacuo. Purification of the residue by size exclusion column
chromatography (LH-20, CH2Cl2/MeOH, 1/1) and silica gel
column chromatography (CH2Cl2/acetone, 99/1, v/v) afforded
30 as a white glass (98 mg, 56%): Rf 0.48 (CH2Cl2/acetone,
98/2, v/v); FAB-MS m/z 1069 (M+ + Na); 13C NMR (CDCl3) δ
169.2, 165.8, and 165.0 (CH3CO, 2 C6H5CO), 138.3, 138.2,
138.0, and 133.1-127.3 (4 C6H5CH2, 2 C6H5CO), 100.3 (C-1′),
85.8 (C-1), 82.9 (C-3′), 77.7 (C-4′), 75.3 (C-4), 74.9, 74.8, and
74.7 (C-5′, 2 C6H5CH2), 73.8, 73.3, and 73.1 (C-2′, 2 C6H5CH2),
72.3 (C-2), 71.3 (C-3), 71.1 (C-5), 68.5 and 67.7 (C-6,6′), 62.2
(SCH), 40.9, 39.6, and 32.0-26.1 (2 C6H11), 20.8 (CH3CO); 1H
NMR (CDCl3) δ 8.03-7.97 and 7.51-7.07 (m, 30H, 4 C6H5-
CH2, 2 C6H5CO), 5.79 (dd, 1H, H-3, J 2,3 10.3, J 3,4 9.0 Hz), 5.62
(d, 1H, H-1, J 1,2 5.9 Hz), 5.28 (dd, 1H, H-2), 4.89 (dd, 1H, H-2′,
J 1′,2′ 8.0, J 2′,3′ 9.3), 4.9-4.1 (m, 16H, 4 C6H5CH2), 4.50 (d, 1H,
H-1′), 4.40 (m, 1H, H-5), 4.20 (d, 1H, H-4), 3.95 (dd, 1H, H-6a,
J 5,6a 2.9, J 6a,6b -11.0 Hz), 3.63 (dd, 1H, H-6b, J 5,6b 1.9 Hz), 3.56
(t, 1H, H-4′, J 3′,4′J 4′,5′ 9.2 Hz), 3.44 (t, 1H, H-3′), 3.32 (m, 2H,
H-6′a, 6′b), 3.14 (dt, 1H, H-5′, J 5′,6a′J 5′,6′b 3.0 Hz), 2.31 (t, 1H,
SCH, J 5.9 Hz), 1.84 (s, 3H, CH3CO), 1.7-0.7 (m, 22H, 2
C6H11); HR FAB-MS calcd for C69H78SO13Na 1169.5061, found
1169.5101.
Dicycloh exylm eth yl 2,3,4-Tr i-O-ben zoyl-6-O-(2,3,4-tr i-
O-ben zoyl-6-O-(2,3,4-tr i-O-ben zyl-6-O-(2,3,4,6-tetr a-O-ben -
zyl-r-D-glu cop yr a n osyl)-r/â-D-glu cop yr a n osyl)-â-D-glu -
copyr an osyl)-1-th io-r-D-glu copyr an oside (33). To a stirred
mixture of 13 (130 mg, 0.09 mmol), 9R (64 mg, 0.09 mmol),
and molecular sieves (4 Å, 0.5 g) in dry CH2Cl2/Et2O (1/1, v/v,
2 mL) were added NIS (21 mg, 0.09 mmol) and TMSOTf (4
µL, 22 µmol). After 5 min of stirring at rt, the reaction mixture
was quenched with TEA (0.02 mL), diluted with CH2Cl2 (60
mL), and washed with aqueous Na2S2O3 (2 × 15 mL, 15%, w/v)
and H2O (2 × 15 mL). The organic phase was dried (MgSO4),
filtered, and concentrated in vacuo. Purification of the residue
by silica gel column chromatography (dichloromethane/
acetone, 99/1, v/v), followed by size exclusion column chroma-
tography (LH-60, CH2Cl2/MeOH, 1/1, v/v) afforded 33 as a
white glass (102 mg, 55%): Rf 0.44 (CH2Cl2/acetone, 98/2, v/v);
1
FAB-MS m/z 2139 (M+ + Na); H NMR (CDCl3) δ 8.10-7.10
(m, 65H, 7 C6H5CH2, 6 C6H5CO), 5.86 (t, 1H, H-3, J 2,3J 3,4 9.9
Hz), 5.84 (t, 1H, H-3′, J 2′,3′J 3′,4′ 9.9 Hz), 5.55 (d, 1H, H-1, J 1,2
5.8 Hz), 5.49 (t, 1H, H-4′, J 4′,5′ 9.9 Hz), 5.46 (dd, 1H, H-2′, J 1′,2′
7.9 Hz), 5.44 (t, 1H, H-4, J 4,5 9.9 Hz), 5.05 (dd, 1H, H-2), 4.94-
4.38 (m, 14H, 7 C6H5CH2), 4.93 (d, 1H, H-1′′, J 1′′,2′′ 3.5 Hz),
4.86 (d, 1H, H-1′), 4.61 (d, 1H, H-1′′′, J 1′′′,2′′′ 3.6 Hz), 4.60 (m,
1H, H-5, J 5,6a 3.0, J 5,6b 3.3 Hz), 4.19 (dd, 1H, H-6a), 3.92 (dd,
1H, H-3′′, J 2′′,3′′ 10.5, J 3′′,4′′ 8.5 Hz), 3.89 (m, 1H, H-5′, J 5′a,6′a
5.2 Hz, J 5′,6′b 2.7 Hz), 3.87 (dd, 1H, H-3′′′, J 2′′′,3′′′ 9.5 Hz, J 3′′′,4′′′
8.2 Hz), 3.81 (dd, 1H, H-6′a, J 6′a,6′b -11.2 Hz), 3.73 (dd, 1H,
H-6b), 3.71-3.56 (m, 8H, H-4′′, H-5′′, H-6′′a, H-6′′b, H-4′′′,
H-5′′′, H-6′′′a, H-6′′′b), 3.54 (dd, 1H, H-6′b), 3.48 (dd, 1H, H-2′′),
3.30 (dd, 1H, H-2′′′), 2.21 (m, 1H, SCH), 1.8-0.6 (m, 22H, 2
C6H11); HR FAB-MS calcd for C128H130SO26Na 2137.8469, found
2137.8359.
Meth yl 2,3,4-Tr i-O-ben zyl-6-O-(2,3,4-tr i-O-ben zoyl-6-O-
(2,3,4-t r i-O-b en zoyl-6-O-(2,3,4-t r i-O-b en zyl-6-O-(2,3,4,6-
tetr a-O-ben zyl-r-D-glu copyr an osyl)-r/â-D-glu copyr an osyl)-
â-D -g lu c o p y r a n o s y l)-â-D -g lu c o p y r a n o s y l)-r-D -g lu c o -
p yr a n osid e (34). To a stirred mixture of 33 (101 mg, 0.05
mmol), 14 (45 mg, 0.10 mmol), and molecular sieves (4 Å, 1.5
g) in dry CH2Cl2/Et2O (1/1, v/v, 3 mL) were added NIS (70 mg,
0.31 mmol) and TMSOTf (8 µL, 44 µmol). After 20 min of
stirring at rt, the reaction mixture was quenched with TEA
(0.01 mL), diluted with CH2Cl2 (50 mL), and washed with
aqueous Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O (2 × 15 mL).
The organic phase was dried (MgSO4), filtered, and concen-
trated in vacuo. Purification of the residue by silica gel column
chromatography (CH2Cl2/acetone, 96/4), followed by size exclu-
sion column chromatography (LH-60, CH2Cl2/MeOH, 1/1, v/v),
afforded 34 as a white glass (70 mg, 62%): Rf 0.39 (CH2Cl2/
acetone, 96/4, v/v); FAB-MS m/z 2391 (M+ + Na); 1H NMR
(CDCl3) δ 7.90-6.90 (m, 80H, 10 C6H5CH2, 6 C6H5CO), 5.70
(t, 1H, H-3′′, J 2′′,3′′J 3′′,4′′ 9.5 Hz), 5.64 (t, 1H, H-3′, J 2′,3′J 3′,4′ 9.5
Hz), 5.49 (t, 1H, H-4′′, J 4′′,5′′ 9.5 Hz), 5.37-5.31 (m, 2H, H-2′,
H-2′′), 5.22 (t, 1H, H-4′, J 4′,5′ 9.5 Hz), 4.86 (d, 1H, H-1′′, J 1′′,2′′
7.3 Hz), 4.83 (d, 1H, H-1′′′, J 1′′′,2′′′ 3.5 Hz), 4.56 (d, 1H, H-1′′′′,
J 1′′′′,2′′′′ 3.9 Hz), 4.52 (d, 1H, H-1, J 1,2 3.5 Hz), 4.38 (d, 1H, H-1′,
J 1′,2′ 7.8 Hz), 4.88-4.25 and 4.08 (m, 23H, 10 C6H5CH2), 3.97
(m, 1H, H-6′′a), 3.91-3.21 (m, 20H, H-2, H-3, H-4, H-5, H-6a,
H-6b, H-5′, H-6′a, H-6′b, H-5′′, H-6′′b, H-2′′′, H-3′′′, H-4′′′, H-5′′′,
H-6′′′a, H-6′′′b, H-2′′′′, H-3′′′′, H-4′′′′, H-5′′′′, H-6′′′′a, H-6′′′′b),
3.26 (s, 3H, OCH3); HR FAB-MS calcd for C143H138O32Na
2390.9102, found 2390.9196.
Meth yl 2,3,6-Tr i-O-ben zyl-4-O-(2,3,4,6-tetr a -O-ben zoyl-
â-D-glu copyr an osyl)-r-D-glu copyr an oside (32). To a stirred
mixture of compound 4R (179 mg, 0.23 mmol), methyl 2,3,6-
tri-O-benzyl-R-D-glucopyranoside 31 (135 mg, 0.29 mmol), and
molecular sieves (4 Å, 0.8 g) in dry CH2Cl2 (8.5 mL) were added
NIS (300 mg, 1.33 mmol) and TMSOTf (37 µL, 0.07 mmol).
After 30 min of stirring at rt, the reaction mixture was
quenched with TEA (0.05 mL), diluted with CH2Cl2 (60 mL),
transferred to a separatory funnel, and washed with aqueous
Na2S2O3 (2 × 15 mL, 15%, w/v) and H2O (2 × 15 mL). The
organic phase was collected, dried (MgSO4), filtered, and
concentrated in vacuo. Purification of the residue by size
exclusion column chromatography (LH-20, CH2Cl2/MeOH, 1/1)
afforded 32 as a white glass (145 mg, 62%): Rf 0.20 (CH2Cl2/
acetone, 8/2, v/v); [R]25D +2.64° (c 1); FAB-MS m/z 1065 (M+
+
Na); 13C NMR (CDCl3) δ 166.0-164.8 (4 C6H5CO), 139.3-127.1
(4 C6H5CO, 3 C6H5CH2), 100.4 (C-1′), 98.5 (C-1), 79.9, 78.8,
77.3, 73.2, 72.2, 72.2, 71.8, 69.9, and 69.5 (C-2,3,4,5,2′,3′,4′,5′),
75.3 and 73.6 (3 C6H5CH2), 67.6 and 63.1 (C-6, 6′), 55.3 (OCH3);
1H NMR (CDCl3), δ 7.90-7.10 (m, 35H, 4 C6H5CO, 3 C6H5-
CH2), 5.54 (t, 1H, H-3′, J 2′,3′J 3′,4′ 9.6 Hz), 5.47 (t, 1H, H-4′, J 4′,5′
9.6 Hz), 5.39 (dd, 1H, H-2′, J 1′,2′ 8.0 Hz), 5.00, 4.73, 4.678, 4.67,
4.51, and 4.27 (6 d, 6H, 3 C6H5CH2), 4.683 (d, 1H, H-1′, J 1′,2′
8.0 Hz), 4.47 (d, 1H, H-1, J 1,2 3.8 Hz), 4.32 (dd, 1H, H-6a′, J 5′,6a′
3.3, J 6′a,6′b -12.2 Hz), 4.18 (dd, 1H, H-6b′, J 5′,6b′ 3.3 Hz), 3.89
(dd, 1H, H-4, J 3,4 9.2, J 4,5 9.5 Hz), 3.80 (t, 1H, H-3, J 2,3 9.2
Hz), 3.67-3.60 (m, 2H, H-6a, H-5′), 3.42 (m, 1H, H-5), 3.38
(dd, 1H, H-2), 3.34 (dd, 1H, H-6b, J 5,6b 1.9, J 6a,6b -10.8 Hz),
3.20 (s, 3H, OCH3); HR FAB-MS calcd for C62H58O15Na
1065.3673, found 1065.3633.
Ack n ow led gm en t. This work was supported by
GlaxoWellcome Research and Development Ltd. (Re-
search Studentship for R.G.).
Su p p or tin g In for m a tion Ava ila ble: NMR and COSEY
spectra (44 pages). This material is contained in libraries on
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