S-benzoxazolyl as a stable protecting moiety and a potent anomeric leaving group in oligosaccharide synthesis

Article abstract of DOI:10.1021/jo071191s

(Chemical Equation Presented) As a part of a program for developing new versatile building blocks for stereoselective glycosylation and convergent oligosaccharide synthesis, we demonstrated that S-benzoxazolyl (SBox) glycosides are stable toward major protecting group manipulations employed in carbohydrate chemistry. On the other hand, they can be glycosidated under relatively mild reaction conditions to afford either 1,2-trans or 1,2-cis-linked disaccharides. Selective and chemoselective activations of the SBox moiety were also proved to be feasible, which was demonstrated by synthesizing a number of oligosaccharide sequences.

Full text of DOI:10.1021/jo071191s

S-Benzoxazolyl as a Stable Protecting Moiety and a Potent
Anomeric Leaving Group in Oligosaccharide Synthesis
Medha N. Kamat, Cristina De Meo, and Alexei V. Demchenko*
Department of Chemistry and Biochemistry, UniVersity of MissourisSt. Louis,
One UniVersity BouleVard, St. Louis, Missouri 63121
demchenkoa@umsl.edu
ReceiVed June 5, 2007
As a part of a program for developing new versatile building blocks for stereoselective glycosylation
and convergent oligosaccharide synthesis, we demonstrated that S-benzoxazolyl (SBox) glycosides are
stable toward major protecting group manipulations employed in carbohydrate chemistry. On the other
hand, they can be glycosidated under relatively mild reaction conditions to afford either 1,2-trans or
1,2-cis-linked disaccharides. Selective and chemoselective activations of the SBox moiety were also proved
to be feasible, which was demonstrated by synthesizing a number of oligosaccharide sequences.
Introduction
(in)es as complimentary glycosyl donors for chemical glyco-
sylation.8 We already demonstrated that this class of compounds
can serve as excellent intermediates in stereoselective glyco-
sylations9-11 and convergent oligosaccharide syntheses via
conceptually novel strategies.12-15 Another important recent
development in this area is the anomeric phosphorylation of
glycosyl thioimidates.16,17
Glycosyl thioimidates, compounds bearing SCR1dNR2 ag-
lycon, have been known for decades, yet their synthetic value
as versatile intermediates in carbohydrate chemistry has only
recently come to the fore.1 Relatively low stability of the
previously studied thioimidates was the major reason the use
of benzothiazolyl,2 pyridin-2-yl,3-5 pyrimidin-2-yl,3,6 imidazolin-
2-yl,3 and 1′-phenyl-1H-tetrazolyl7 glycosides in oligosaccharide
synthesis was limited. Our laboratory has been primarily
investigating a family of substituted oxazol(in)es and thiazol-
(8) Pornsuriyasak, P.; Kamat, M. N.; Demchenko, A. V. ACS Symp. Ser.
2007, 960, 165-189.
(9) Pornsuriyasak, P.; Demchenko, A. V. Chem. Eur. J. 2006, 12, 6630-
6646.
(1) El Ashry, E. S. H.; Awad, L. F.; Atta, A. I. Tetrahedron 2006, 62,
2943-2998.
(10) Demchenko, A. V.; Pornsuriyasak, P.; De Meo, C.; Malysheva, N.
N. Angew. Chem., Int. Ed. 2004, 43, 3069-3072.
(11) Demchenko, A. V.; Malysheva, N. N.; De Meo, C. Org. Lett. 2003,
5, 455-458.
(2) Mukaiyama, T.; Nakatsuka, T.; Shoda, S. I. Chem. Lett. 1979, 487-
490.
(3) Hanessian, S.; Bacquet, C.; Lehong, N. Carbohydr. Res. 1980, 80,
c17-c22.
(4) Woodward, R. B.; Logusch, E.; Nambiar, K. P.; Sakan, K.; Ward,
D. E.; Au-Yeung, B. W.; Balaram, P.; Browne, L. J.; Card, P. J.; Chen, C.
H. J. Am. Chem. Soc. 1981, 103, 3215-3217.
(5) Reddy, G. V.; Kulkarni, V. R.; Mereyala, H. B. Tetrahedron Lett.
1989, 30, 4283-4286.
(6) Chen, Q.; Kong, F. Carbohydr. Res. 1995, 272, 149-157.
(7) Tsuboyama, K.; Takeda, K.; Torii, K.; Ebihara, M.; Shimizu, J.;
Suzuki, A.; Sato, N.; Furuhata, K.; Ogura, H. Chem. Pharm. Bull. 1990,
38, 636-638.
(12) Kamat, M. N.; Demchenko, A. V. Org. Lett. 2005, 7, 3215-3218.
(13) Pornsuriyasak, P.; Demchenko, A. V. Tetrahedron: Asymmetry
2005, 16, 433-439.
(14) Smoot, J. T.; Pornsuriyasak, P.; Demchenko, A. V. Angew. Chem.,
Int. Ed. 2005, 7123-7126.
(15) Pornsuriyasak, P.; Gangadharmath, U. B.; Rath, N. P.; Demchenko,
A. V. Org. Lett. 2004, 6, 4515-4518.
(16) Ferrieres, V.; Blanchard, S.; Fischer, D.; Plusquellec, D. Bioorg.
Med. Chem. Lett. 2002, 12, 3515-3518.
(17) Euzen, R.; Ferrieres, V.; Plusquellec, D. J. Org. Chem. 2005, 70,
847-855.
10.1021/jo071191s CCC: $37.00 © 2007 American Chemical Society
Published on Web 08/04/2007
J. Org. Chem. 2007, 72, 6947-6955
6947

Kamat et al.
D-galacto-, and D-manno series (2, 3, and 4, respectively) are
very efficient glycosyl donors for the synthesis of 1,2-trans-
linked disaccharides. As highlighted in Table 1, reactions with
differently protected glycosyl acceptors 10, 12, 14, 16, 18, and
20 of the D-gluco and D-galacto series gave the corresponding
disaccharides 11, 13, 15, 17, 19, and 21-23 in high yields of
86-95% and complete stereoselectivity. The complete 1,2-trans
stereoselectivity is attributed to the assistance of a participating
substituent at the C-2 position.
Glycosidation of the SBox Derivatives: Synthesis of 1,2-
cis-Glycosides. Stereoselective synthesis of 1,2-cis-glycosides
from SBox glycosyl donors was also investigated. In this case,
we investigated glycosyl donors bearing a nonparticipating
substituent at C-2, perbenzylated SBox glycoside 5 or its 2-O-
benzyl-3,4,6-tri-O-acetyl counterpart 7. Similarly, glycosidations
of the SBox derivatives of the D-manno (3) and D-galacto series
(4 or 8), respectively, were probed. For the highly reactive
perbenzylated glycosyl donors 5 or 6, Cu(OTf)2 was found to
be the promoter of choice. Although reactions performed in 1,2-
DCE were found to be high yielding, the stereoselectivity was
below average (typically R/â 2/1) in the majority of cases. While
no improvement in stereoselectivity was achieved by changing
promoters, significantly higher stereoselectivity was accom-
plished when the glycosylation was performed in toluene-
dioxane (1/3, v/v), a participating solvent mixture.20 As a result
of varying the reaction solvent, significantly improved
stereoselectivity could be achieved (up to R/â 7/1, entries 1-5,
Table 2).
FIGURE 1. Differently protected SBox glycosides of the D-gluco,
D-galacto, and D-manno series.
Side-by-side comparison of an array of structurally related
cyclic thioimidates18 revealed that 1-S-benzoxazolyl (SBox)
derivatives bear major positive traits of a modern glycosyl
donor: accessibility, odorless preparation, stability toward many
reaction conditions employed in carbohydrate chemistry, mild
and selective activation for glycosylation, and excellent stereo-
selectivity. In the preceding paper,19 we demonstrated that the
SBox glycosides 1-9 (Figure 1) can be successfully prepared
from a variety of synthetic precursors and can be applied as
glycosyl donors for stereoselective glycosylation. Herein we
present our thorough evaluation of the SBox derivatives in
glycoside synthesis and their application to the synthesis of a
variety of compounds ranging from relatively simple partially
protected glycosyl acceptors to elaborate oligosaccharide se-
quences.
Application of partially acetylated glycosyl donors 7 or 8 was
found to be especially beneficial for 1,2-cis glycosylation. In a
number of cases, very high or even complete 1,2-cis stereose-
lectivity was achieved in dichloromethane, a solvent that does
not usually favor 1,2-cis glycosylation (see entries 6-14, Table
2). Arguably, the stereoselectivity achieved herein favorably
compares with the best procedures for direct 1,2-cis glycosy-
lation developed to date.21,22 It should be noted that, in spite of
significant improvements that have emerged in the past decade,
stereocontrolled synthesis of 1,2-cis-glycosides still remains a
significant challenge.
Results and Discussion
In the preceding paper, we established the activation pathways
and experimental conditions for the glycosidation of SBox
glycosides;19 herein, we turn our attention to investigating their
properties as glycosyl donors in the formation of various
glycosidic linkages. A unique feature of the SBox glycosyl
donors is that a broad range of conceptually different approaches
can be applied to their glycosidation. The reaction conditions
range from traditional thioglycoside activators: MeOTf and NIS/
TfOH to mildly electrophilic metal salts, such as AgOTf and
Cu(OTf)2. In addition, protic and Lewis acids were also shown
as promoters for this class of compounds, although at this stage
the effectiveness of this type of activation is modest.
Glycosidation of the SBox Derivatives: Synthesis of 1,2-
trans-Glycosides. As previously reported,19 per-acetylated SBox
glycosides (such as 1) provide somewhat compromised results
due to competing acetyl migration from the O-2 of glycosyl
donor to the free hydroxyl of the glycosyl acceptor.19 Hence,
our main effort for the synthesis of 1,2-trans-linked glycosides
has been focused on the investigation of the perbenzoylated
SBox glycosides (2-4). Also, having already ascertained that
the perbenzoylated SBox glycosides could be efficiently acti-
vated with AgOTf or MeOTf, our main effort has been directed
on the application of these two promoters. Herein, we report
that perbenzoylated SBox glycosyl donors of the D-gluco,
Stability of the 1-SBox Glycosides: Synthesis of Glycosyl
Acceptors. A significant drawback of many classes of glycosyl
donors is their poor stability toward protecting group manipula-
tions. For instance, labile glycosyl donors such as bromides,23,24
trichloroacetimidates,25 phosphites,26 phosphates,27 etc. should
be obtained directly prior to the glycosylation. In this respect,
stable glycosyl donors, such as fluorides,28,29 alkyl or aryl
(20) Demchenko, A.; Stauch, T.; Boons, G. J. Synlett 1997, 818-820.
(21) Demchenko, A. V. Curr. Org. Chem. 2003, 7, 35-79.
(22) Demchenko, A. V. Synlett 2003, 1225-1240.
(23) Nitz, M.; Bundle, D. R. In Glycoscience: Chemistry and Chemical
Biology; Fraser-Reid, B., Tatsuta, K., Thiem, J., Eds.; Springer: Berlin -
Heidelberg - New York, 2001; Vol. 2, p 1497-1542.
(24) Igarashi, K. AdV. Carbohydr. Chem. Biochem. 1977, 34, 243-283.
(25) Schmidt, R. R.; Jung, K. H. In Carbohydrates in Chemistry and
Biology; Ernst, B., Hart, G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim,
New York, 2000; Vol. 1, p 5-59.
(26) Zhang, Z.; Wong, C. H. In Carbohydrates in Chemistry and Biology;
Ernst, B., Hart, G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim, New York,
2000; Vol. 1, p 117-134.
(27) Plante, O. J.; Palmacci, E. R.; Andrade, R. B.; Seeberger, P. H. J.
Am. Chem. Soc. 2001, 123, 9545-9554.
(18) Ramakrishnan, A.; Pornsuriyasak, P.; Demchenko, A. V. J. Car-
bohydr. Chem. 2005, 24, 649-663.
(19) Kamat, M. N.; Rath, N. P.; Demchenko, A. V. J. Org. Chem. 2007,
72, 6938-6946.
(28) Nicolaou, K. C.; Ueno, H. In PreparatiVe Carbohydrate Chemistry;
Hanessian, S., Ed.; Marcel Dekker, Inc.: New York, 1997, p 313-338.
(29) Mukaiyama, T. Angew. Chem., Int. Ed. 2004, 43, 5590-5614.
6948 J. Org. Chem., Vol. 72, No. 18, 2007

S-Benzoxazolyl in Oligosaccharide Synthesis
TABLE 1. Synthesis of 1,2-trans-Glycosides
a Abbreviation: TE, (2-trimethylsilyl)ethyl. b AgOTf and MeOTf performed nearly equally well; only the best selected results are presented herein.
thioglycosides,30,31 O-alkenyl glycosides,32,33 or selenoglyco-
sides,34 offer a significant advantage in that a stable leaving
group can also serve as a temporary anomeric protecting group.
This would allow the installation of a required protecting group
pattern and preclude additional manipulations at the anomeric
center prior to glycosylation. The evaluation of the compatibility
of SBox glycosides with reaction conditions required for
installing or removing common classes of protecting groups
seemed to be a logical step in the systematic study of these
novel derivatives.
(30) Garegg, P. J. AdV. Carbohydr. Chem. Biochem. 1997, 52, 179-
205.
(31) Oscarson, S. In Carbohydrates in Chemistry and Biology; Ernst,
B.; Hart, G. W.; Sinay, P.; Eds.; Wiley-VCH: Weinheim, New York, 2000;
Vol. 1, p 93-116.
(32) Fraser-Reid, B.; Anilkumar, G.; Gilbert, M. B.; Joshi, S.; Kraehmer,
R. In Carbohydrates in Chemistry and Biology; Ernst, B., Hart, G. W.,
Sinay, P., Eds.; Wiley-VCH: Weinheim, New York, 2000; Vol. 1, p 135-
154.
It should be noted that the majority of SBox derivatives
investigated in our laboratory were found to be stable crystalline
compounds that could be stored at ambient temperature and
humidity.19 As to the chemical stability of the SBox glycosides,
we performed a number of experiments that demonstrated the
relatively high stability of the SBox moiety. Thus, preliminary
experiments with SBox derivative 7 demonstrated that this
(33) Boons, G. J. In Glycoscience: Chemistry and Chemical Biology;
Fraser-Reid, B.; Tatsuta, K.; Thiem, J.; Eds.; Springer: Berlin - Heidelberg
- New York, 2001; Vol. 1, p 551-581.
(34) Mehta, S.; Pinto, B. M. J. Org. Chem. 1993, 58, 3269-3276.
J. Org. Chem, Vol. 72, No. 18, 2007 6949

Kamat et al.
TABLE 2. Synthesis of 1,2-cis-Glycosidesa
6950 J. Org. Chem., Vol. 72, No. 18, 2007

S-Benzoxazolyl in Oligosaccharide Synthesis
Table 2. (Continued)
a Extended table can be found in the Supporting Information. b Toluene-dioxane (1/3, v/v). c No formation of the â-anomer has been detected by 1H
NMR (R/â > 95/5).
SCHEME 1
SCHEME 2
41, Scheme 1), the results with compounds 1 or 9 were rather
surprising. To overcome this problem, the deacetylation of 1
was performed using a saturated solution of ammonia in MeOH
(pH e 8). Simple precipitation from the reaction mixture
afforded the desired reaction intermediate 45, which was found
to be compatible with conventional tritylation, benzoylation, and
detritylation conditions. As a result, derivatives 2 and 46 were
obtained in good overall yields (Scheme 2).
compound could be efficiently deacetylated under conventional
Zemplen conditions.35 The intermediate 41 was found to be
stable under standard reaction conditions for the introduction
of alkyl, acyl, and acetal substituents (Scheme 1).36 As a result,
we accomplished the syntheses of a range of differently
protected building blocks 5 and 42-44 containing the SBox
anomeric moiety.
However, when Zemplen conditions (catalytic MeONa in
MeOH) were applied to the deprotection of the tetraacetyl
derivative 1 or its triacetylated counterpart 9, only traces of the
expected intermediate 45 were detected in the reaction mixture.
Disappointingly, methyl D-glucopyranoside (R/â ) 1.3/1) was
found to be the major product of this reaction s an indication
of the anomeric leaving group displacement. Taking into
consideration that deacetylation of the 2-benzyl derivative 7
proceeded in a nearly quantitative yield (see the synthesis of
However, when the intermediate 45 was subjected to strongly
basic reaction conditions (BnBr and NaH in DMF, see the
attempted synthesis of 5, Scheme 2), departure of the SBox
moiety resulted in the formation of D-glucose, which was
subsequently benzylated. It should be reminded that per-
benzylated SBox derivative 5 could be readily obtained from
the 2-benzyl SBox intermediate 41 under the same reaction
conditions in 90% yield. The disparity of results obtained from
2-benzyl (7 f 41 f 5) and 2-acyl/hydroxyl derivatives (1 f
45 f 5) made us believe that while the SBox moiety itself is
stable toward strong bases (MeONa, NaH, NaOH, see for
example the syntheses of 5 and 41, Scheme 1), it readily departs
upon the nucleophilic attack of the deprotonated C-2 hydroxyl
(35) Wolfrom, M. L.; Thompson, A. In Methods in Carbohydrate
Chemistry; Whistler, R. L., Wolfrom, M. L., Eds.; Academic Press: New
York - London, 1963; Vol. 2, p 215-220.
(36) Wuts, P. G. M.; Greene, T. W. Greene’s ProtectiVe Groups in
Organic Synthesis; 4th ed.; Wiley-Interscience: New York, 2007.
J. Org. Chem, Vol. 72, No. 18, 2007 6951

Kamat et al.
oped in our laboratory.40 To explore this possibility, we
performed the coupling of the S-ethyl disaccharide donors 50
or 52 with glycosyl acceptors 48 or 53 in the presence of MeOTf
to afford the corresponding trisaccharide derivatives 51 or 54
in 92 or 90% yield, respectively (Scheme 4). The O-pentenyl
moiety of the trisaccharide donor 54 was then activated for the
reaction with glycosyl acceptor 14 in the presence of NIS/TfOH.
As a result, a tetrasaccharide derivative 55 was isolated in 73%
yield. These examples serve as a clear illustration of the
enhanced ability to obtain oligosaccharides via sequential
activation in a convergent fashion with no additional protecting/
leaving group manipulations between the glycosylation steps.
SCHEME 3
on the anomeric center (see the proposed reaction intermediate
A, Scheme 2).
SBox Glycosides as Building Blocks in Expeditious Oli-
gosaccharide Synthesis. An important feature of a glycosyl
donor would be its applicability to multistep oligosaccharide
synthesis via expeditious building block based pathways.37
Having completed the stereoselectivity studies (see Tables 1
and 2), we wanted to investigate whether the SBox glycosides
could be chemoselectively activated in accordance with the
armed-disarmed approach developed by Fraser-Reid.38,39 Ac-
cording to this strategy, a significantly more reactive (armed)
benzylated glycosyl donor can be chemoselectively activated
in the presence of the acylated (disarmed) derivative to afford
a disaccharide. We found that the SBox glycosides also follow
general chemoselectivity principle. Thus, armed SBox glycoside
donor 5 could be activated over electronically disarmed SBox
glycosyl acceptor 46 in the presence of Cu(OTf)2 (Scheme 3).
Therefore, obtained disaccharide 47 bearing the SBox leaving
group can then be coupled with a suitable acceptor under typical
reaction conditions for the SBox activation.
Our other aim was to determine whether the SBox derivatives
could be coupled with glycosyl acceptors containing other types
of anomeric leaving groups. The key requirement for such
activation would be the availability of a promoter that could
selectively activate the SBox moiety over a stable anomeric
moiety of the glycosyl acceptor, such as S-ethyl. Our initial
assumption was that such selective activation could be ac-
complished using AgOTf as a promoter. Thus, in studies with
glycosyl donors 2 and 7, we chose S-ethyl glycoside 49 as
glycosyl acceptor (Scheme 4). Remarkably, the glycosylations
involving selective activation of the SBox leaving group
afforded the corresponding disaccharide products 50 and 52 with
excellent stereoselectivity and yields of 98-99%. Very impor-
tantly, no side products involving self-condensation of the
glycosyl acceptor were detected. Similarly, the SBox moiety
could be activated in the presence of the O-pentenyl moiety.11
Furthermore, in an independent study of the STaz glycosidation
protocol, it was also established that the SBox moiety can be
selectively activated over the STaz anomeric moiety using Cu-
(OTf)2 as a promoter.9
Conclusions
Based on the results presented, we conclude that the SBox
glycosides are stable toward majority of protecting group
manipulations employed in carbohydrate chemistry. It has been
demonstrated that the SBox moiety is even stable toward strong
bases if the O-2 position of the pyranose ring is protected with
a stable moiety, such as benzyl. When the protection is removed,
stability of the SBox moiety significantly decreases. The SBox
glycosides were also found to be suitable building blocks for
chemoselective armed-disarmed activations and for selective
sequential activations over other classes of leaving groups.
Experimental Part
For general procedures for the preparation of di- and oligosac-
charides, refer to the preceding article: method A, MeOTf; method
B, AgOTf; method C, Cu(OTf)2.19
Methyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzoyl-â-D-
glucopyranosyl)-â-D-galactopyranoside (11) was obtained using
method A from 2 and 1041 in 92% yield. Analytical data for 11
were essentially the same as reported previously.42
6-O-(2,3,4,6-Tetra-O-benzoyl-â-D-glucopyranosyl)-1,2:3,4-di-
O-isopropylidene-R-D-galactopyranose (13) was obtained from
2 and 12 using method B in 91% or by method C in 70% yield.
Analytical data for 13 were essentially the same as reported
previously.9
Methyl 6-O-(2,3,4,6-tetra-O-benzoyl-â-D-glucopyranosyl)-
2,3,4-tri-O-benzyl-R-D-glucopyranoside (15) was obtained using
method A from 2 and 1443 in 95% yield. Analytical data for 15
were essentially the same as reported previously.44
2-Trimethylsilylethyl 2-O-(2,3,4,6-tetra-O-benzoyl-â-D-glu-
copyranosyl)-3-O-benzyl-4,6-O-benzylidene-â-D-galactopyrano-
side (17) was obtained using method A from 2 and 1645 in 94%
yield. Analytical data for 17: Rf ) 0.37 (ethyl acetate-hexane,
3/7, v/v); [R]22 39.9 (c ) 1.0, CHCl3); H NMR δ 0.00 (s, 9H,
1
D
SiCH3), 1.01 (t, 2H, J ) 8.7 Hz, CH2TMS), 3.40 (dd, 1H, J3,4
)
a
3.6 Hz, H-3), 3.63 (m, 1H, CH2 ), 3.80 (dd, 1H, H-4), 3.87 (dd,
b
1H, J5,6a ) 2.7, J6a,6b ) 12.4, H-6a), 3.97-4.27 (m, 5H, CH2 , H-2′,
The key feature of the oligosaccharide synthesis via selective
activation is that the disaccharides obtained can be immediately
used in subsequent glycosidation. In the case of the disaccharides
50 and 52, the second step activation should be feasible in the
presence of NIS/TfOH or other suitable activators for S-alkyl/
aryl moieties.30-32 Additionally, selective activation of S-ethyl
over the O-pentenyl moiety can be achieved in the presence of
MeOTf in accordance with the semi-orthogonal strategy devel-
5, 5′, 6b), 4.35 (dd, 2H, J2 ) 12.8 Hz, CH2Ph), 4.42 (d, 1H, J1,2
)
7.7 Hz, H-1), 4.50 (dd, 1H, H-6b′), 4.65 (dd, 1H, J5′,6a′ ) 3.8 Hz,
J6a′,6b′ ) 12.6, H-6a′), 5.25 (s, 1H, CHPh), 5.39 (d, 1H, J1′,2′ ) 7.9
(40) Demchenko, A. V.; De Meo, C. Tetrahedron Lett. 2002, 43, 8819-
8822.
(41) Valashek, I. E.; Shakhova, M. K.; Minaev, V. A.; Samokhvalov,
G. I. Zh. Obshch. Khim. 1974, 44, 1161-1164.
(42) Ziegler, T.; Sutoris, H.; Glaudemans, C. P. J. Carbohydr. Res. 1992,
229, 271-291.
(37) Demchenko, A. V. Lett. Org. Chem. 2005, 2, 580-589.
(38) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J.
Am. Chem. Soc. 1988, 110, 5583-5584.
(39) Fraser-Reid, B.; Udodong, U. E.; Wu, Z. F.; Ottosson, H.; Merritt,
J. R.; Rao, C. S.; Roberts, C.; Madsen, R. Synlett 1992, 927-942 and
references therein.
(43) Veeneman, G. H.; van Boom, J. H. Tetrahedron Lett. 1990, 31,
275-278.
(44) Hashimoto, S.; Honda, T.; Ikegami, S. J. Chem. Soc., Chem.
Commun. 1989, 685-687.
(45) Jansson, K.; Ahlfors, S.; Frejd, T.; Kihlberg, J.; Magnusson, G.;
Dahmen, J.; Noori, G.; Stenvall, K. J. Org. Chem. 1988, 53, 5629-5647.
6952 J. Org. Chem., Vol. 72, No. 18, 2007

S-Benzoxazolyl in Oligosaccharide Synthesis
SCHEME 4
Hz, H-1′), 5.65 (dd, 1H, J2′,3′ ) 8.7 Hz, H-2′), 5.79 (dd, 1H, J4′,5′
) 9.4 Hz, H-4′), 5.86 (dd, 1H, J3′,4′ ) 9.5 Hz, H-3′); 13C NMR δ
55.4, 60.6, 62.9, 66.8, 67.1, 68.8, 69.1, 70.1, 70.2, 70.5, 73.6, 75.2,
75.9, 76.3, 77.4, 77.9, 79.1, 80.4, 82.3, 97.9, 98.1, 127.8 (×3),
128.0, 128.1 (×3), 128.3 (×2), 128.5 (×2), 128.6 (×7), 128.7 (×5),
128.8 (×2), 129.2, 129.3, 129.5, 129.9 (×4), 130.0 (×2), 130.1,
133.2, 133.3, 133.6, 133.9, 134.3, 138.4 (x 2), 138.9 ppm; HR-
FAB MS [M + Na]+ calcd for C59H60NaO15Si 1059.3579, found
1059.3589.
Methyl 3-O-(2,3,4,6-tetra-O-benzoyl-â-D-glucopyranosyl)-2-
O-benzyl-4,6-O-benzylidene-R-D-glucopyranoside (19) was ob-
tained using method A from 2 and 1846 in 86% yield. Analytical
data for 19 were essentially the same as reported previously.47
Methyl 4-O-(2,3,4,6-tetra-O-benzoyl-â-D-glucopyranosyl)-
2,3,6-tri-O-benzyl-R-D-glucopyranoside (21) was obtained using
method A from 2 and 2048 in 86% yield. Analytical data for 21
were essentially the same as reported previously.9
Methyl 6-O-(2,3,4,6-tetra-O-benzoyl-â-D-galactopyranosyl)-
2,3,4-tri-O-benzyl-R-D-glucopyranoside (22) was obtained using
method B from 3 and 14 in 92% yield. Analytical data for 22 were
essentially the same as reported previously.49
Methyl 6-O-(2,3,4,6-tetra-O-benzoyl-R-D-mannopyranosyl)-
2,3,4-tri-O-benzyl-R-D-glucopyranoside (23) was obtained using
method A from 4 and 14 in 92% yield Analytical data for 23 were
essentially same as reported previously.9
Methyl 2-O-benzyl-3-O-(2,3,4,6-tetra-O-benzyl-D-glucopyra-
nosyl)-4,6-O-benzylidene-R-D-glucopyranoside (26) was obtained
using method C from 5 and 18 in toluene-dioxane (1:3, v/v, 1
mL) in 65% (R/â ) 4/1) or in 1,2-DCE in 89% (R/â ) 3/1) yield.
Analytical data for 26 were essentially the same as reported
previously.52
Methyl 2-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranosyl)-3,4,6-
tri-O-benzyl-R-D-glucopyranoside (28) was obtained using method
C from 5 and 2753 in toluene-dioxane (1/3, v/v, 1 mL) in 68%
(R/â ) 7/1) or in 1,2-DCE in 61% (R/â ) 2/1) yield. Analytical
data for R-28 were essentially the same as reported previously.9
Methyl 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-D-glu-
copyranosyl)-R-D-glucopyranoside (29) was obtained using method
C from 5 and 20 in toluene-dioxane (1/3, v/v, 1 mL) in 67% (R/â
) 3/1) or in 1,2-DCE in 41% (R/â ) 1.5/1) yield. Analytical data
for 29 were essentially the same as reported previously.54
Methyl 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-D-man-
nopyranosyl)-R-D-glucopyranoside (30) was obtained using method
A from 6 and 20 in 83% yield (R/â ) 1/5.9). Analytical data for
30 were essentially the same as reported previously.55
Methyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzyl-D-
mannopyranosyl)-R-D-glucopyranoside (32) was obtained using
method A from 6 and 31 in 72% yield (R/â ) 1/2.2). Analytical
data for 32 were essentially the same as reported previously.55
Methyl 2-O-benzyl-3-O-(2,3,4,6-tetra-O-benzyl-D-mannopy-
ranosyl)-4,6-O-benzylidene-R-D-glucopyranoside (33) was ob-
tained using method A from 6 and 18 in 83% yield (R/â ) 1/2.5).
Analytical data for 33 were essentially the same as reported
previously.52
6-O-(3,4,6-Tri-O-acetyl-2-O-benzyl-D-glucopyranosyl)-1,2:3,4-
di-O-isopropylidene-R-D-galactopyranose (34) was obtained using
method B from 7 and 12 in 99% yield (R/â ) 11/1). Selected
analytical data for R-34: Rf ) 0.35 (ethyl acetate-hexane, 1/1,
Methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-benzyl-D-glu-
copyranosyl)-R-D-glucopyranoside (24) was obtained using method
C from 5 and 14 in toluene - dioxane (1/3, v/v, 1 mL) in 95%
yield (R/â ) 6/1). Analytical data for 24 were essentially the same
as reported previously.50
6-O-(2,3,4,6-Tetra-O-benzyl-D-glucopyranosyl)-1,2:3,4-di-O-
isopropylidene-R-D-galactopyranose (25) was obtained using
method C from 5 and 12 in toluene-dioxane (1 mL, 3/1, v/v) in
89% yield (R/â ) 5.4/1). Analytical data for 25 were essentially
the same as reported previously.51
(51) Grayson, E. J.; Ward, S. J.; Hall, A. L.; Rendle, P. M.; Gamblin,
D. P.; Batsanov, A. S.; Davis, B. G. J. Org. Chem. 2005, 70, 9740-9754.
(52) Dasgupta, F.; Garegg, P. J. Carbohydr. Res. 1990, 202, 225-238.
(53) Sollogoub, M.; Das, S. K.; Mallet, J. M.; Sinay, P. C. R. Acad. Sci.
Ser. 2 1999, 2, 441-448.
(54) Pougny, J. R.; Nassr, M. A. M.; Naulet, N.; Sinay, P. NouVeau J.
Chem. 1978, 2, 389-395.
(55) Kim, K. S.; Lee, Y. J.; Kim, H. Y.; Kang, S. S.; Kwon, S. Y. Org.
Biomol. Chem. 2004, 2, 2408-2410.
(46) Kondo, Y. Agric. and Biol. Chem. 1975, 39, 1879-1881.
(47) Dasgupta, F.; Garegg, P. J. Carbohydr. Res. 1988, 177, C13-C17.
(48) Garegg, P. J.; Hultberg, H. Carbohydr. Res. 1981, 93, C10-C11.
(49) Codee, J. D. C.; Van den Bos, L. J.; Litjens, R. E. J. N.; Overkleeft,
H. S.; Van Boeckel, C. A. A.; Van Boom, J. H.; Van der Marel, G. A.
Tetrahedron 2004, 60, 1057-1064.
(50) Eby, R.; Schuerch, C. Carbohydr. Res. 1975, 39, 33-38.
J. Org. Chem, Vol. 72, No. 18, 2007 6953

Kamat et al.
v/v); 1H NMR δ 1.26, 1.27, 1.30, 1.34 (4 s, 12H, 4 × CCH3), 2.01,
2.02, 2.08 (3 s, 9H, 3 × COCH3), 3.48 (dd, 1H, J2′,3′ ) 9.3 Hz,
H-2′), 3.6 (m, 2H, H-6a,6b), 3.96 (dd, 1H, J6a′,6b′ ) 12.4 Hz, H-6b′),
3.98 (m, 1H, H-5), 4.02 (m, 1H, H-5′), 4.23 (dd, 1H, J5′,6a′ ) 4.1
Hz, H-6a′), 4.24 (dd, 1H, J2′,3′ ) 9.4 Hz, H-2′), 4.27 (dd, 1H, J4,5
) 1.9 Hz, H-4), 4.51 (dd, 1H, J3,4 ) 2.5 Hz, H-3), 4.56 (dd, 2H,
J2 ) 12.2 Hz, CH2Ph), 4.88 (d, 1H, J1′,2′ ) 3.6 Hz, H-1′), 4.90 (dd,
1H, J4′,5′ ) 9.9 Hz, H-4′), 5.36 (dd, 1H, J3′,4′ ) 9.6 Hz, H-3′), 5.43
(d, 1H, J1,2 ) 4.5 Hz, H-1); 13C NMR δ 20.9, 21.0 (× 2), 24.8,
25.2, 26.3, 26.4, 62.2, 66.5, 67.4, 67.7, 68.8, 70.8 (×2), 71.0, 72.2,
72.5, 96.5, 97.44, 109.0, 109.4, 127.9 (×2), 128.2, 128.7 (×2),
138.0, 170.1, 170.4, 171.0 ppm; HR-FAB MS [M + Na]+ calcd
for C31H42NaO14 661.2472, found 661.2468.
J1′,2′ ) 3.4, H-1′), 5.25 (dd, 1H, J3′,4′ ) 3.8 Hz, H-3′), 5.36 (dd,
1H, J4′,5′ ) 0.8 Hz, H-4′), 5.49 (dd, 1H, J3,4 ) 3.2 Hz, H-3), 5.69
(dd, 1H, J2,3 ) 9.9 Hz, H-2), 5.80 (dd, 1H, J4,5 ) 1.1 Hz, H-4),
7.21-8.09 (m, 20H, aromatic); 13C NMR δ 20.8, 20.9, 21.0, 29.9,
57.5, 66.9, 67.0, 68.7, 69.1, 69.7, 70.1, 72.0, 72.9, 73.4, 73.6, 97.6,
102.6, 128.2 (×2), 128.5 (×2), 128.6 (×2), 128.7 (×2), 128.9 (×2),
129.1, 129.3, 129.6, 130.0 (×4), 130.2 (×2), 133.4 (×2), 133.9,
138.2, 142.1, 142.4, 142.6, 165.7 (×2), 165.9, 170.2, 170.3, 170.6;
HR-FAB MS [M + Na]+ calcd for C47H48NaO17 907.2789, found
907.2798.
6-O-(3,4,6-Tri-O-acetyl-2-O-benzyl-D-galactopyranosyl)-1,2:
3,4-di-O-isopropylidene-R-D-galactopyranose (40) was obtained
using method B from 8 and 12 in 99% yield (R/â 5/1). Selected
analytical data for R-40: Rf ) 0.35 (ethyl acetate-hexane, 1/1,
v/v); 1H NMR δ 1.29, 1.33, 1.45, 1.56 (4 s, 12H, 4 × CCH3), 1.99,
2.05, 2.11 (3 s, 9H, 3 × COCH3), 3.48 (dd, 1H, J2′,3′ ) 9.3 Hz,
H-2′), 3.6 (m, 2H, H-6a, 6b), 3.96 (dd, 1H, J6a′,6b′ ) 12.4 Hz, H-6b′),
3.98 (m, 1H, H-5), 4.02 (m, 1H, H-5′), 4.23 (dd, 1H, J5′,6a′ ) 4.1
Hz, H-6a′), 4.24 (dd, 1H, J2′,3′ ) 9.4 Hz, H-2′), 4.27 (dd, 1H, J4,5
) 1.9 Hz, H-4), 4.51 (dd, 1H, J3,4 ) 2.5 Hz, H-3), 4.56 (dd, 2H,
J ) 12.2 Hz, CH2Ph), 4.88 (d, 1H, J1′,2′ ) 3.6 Hz, H-1′), 4.90 (dd,
1H, J4′,5′ ) 9.9 Hz, H-4′), 5.36 (dd, 1H, J3′,4′ ) 9.6 Hz, H-3′), 5.43
(d, 1H, J1,2 ) 4.5 Hz, H-1) ppm; 13C NMR δ 20.9, 21.0, 21.1,
24.8, 25.2, 26.3, 26.4, 62.2, 66.5, 67.4, 67.7, 68.8, 70.8 (×2), 71.0,
72.2, 72.5, 96.5, 97.4, 109.0, 109.4, 127.9 (×2), 128.2, 128.7 (×2),
138.0, 170.1, 170.4, 171.0; HR-FAB MS [M + Na]+ calcd for
C31H42NaO14 661.2472, found 661.2468.
Methyl 6-O-(3,4,6-tri-O-acetyl-2-O-benzyl-R-D-glucopyrano-
syl)-2,3,4-tri-O-benzoyl-â-D-galactopyranoside (35) was obtained
using method B from 7 and 10 in 97% yield (R only). Analytical
data for R-35 were essentially the same as reported previously.9
2-Trimethylsilylethyl 4-O-(3,4,6-tri-O-acetyl-2-O-benzyl-R-D-
glucopyranosyl)-2,3,6-tri-O-benzyl-â-D-galactopyranose (37) was
obtained using method A from 7 and 3656 in 88% yield (R only).
Selected analytical data for R-37: Rf ) 0.39 (ethyl acetate-hexane,
1
3/7, v/v); H NMR δ 0.03 (s, 9H, Si(CH3)3), 0.96 (m, 2H, CH2-
TMS), 1.96, 2.01, 2.02 (3 s, 9H, 3 × COCH3), 3.41 (dd, 1H, J3,4
a
) 3.2 Hz, H-3), 3.50-3.55 (m, 3H, H-5, -OCH2 , H-6b′), 3.60
(dd, 1H, J2′,3′ ) 9.9 Hz, H-2′), 3.70 (dd, 1H, J2,3 ) 10.2 Hz, H-
b
2), 3.87 (dd, 1H, J6a,6b ) 12.8 Hz, H-6a), 3.99 (m, 1H, -OCH2 ),
4.00 (m, 1H, H-6a′), 4.02 (dd, 1H, H-4), 4.32 (s, 2H, CH2Ph), 4.34
(d, 1H, J1,2 ) 11.3 Hz, H-1), 4.40 (m, 1H, H-5′), 4.61 (s, 2H, CH2-
Ph), 4.71 (s, 2H, CH2Ph), 4.91 (dd, 2H, J2 ) 11.1 Hz, CH2Ph),
4.97 (dd, 1H, J4′,5′ ) 10.2 Hz, H-4′), 5.11 (d, 1H, J1′,2′ ) 3.6 Hz,
H-1′), 5.51 (dd, 1H, J3′,4′ ) 9.6 Hz, H-3′), 7.19-7.42 (m, 20H,
aromatic) ppm; 13C NMR δ -1.0 (×3), 19.0, 21.1 (×2), 21.3, 61.8,
67.9 (×2), 68.9, 69.0, 72.7, 73.6 (×3), 75.3, 76.5, 79.5, 80.7, 99.5,
104.1, 128.03 (×6), 128.1, 128.2 (×3), 128.6 (×2), 128.7 (×2),
128.8 (×6), 138.3, 138.5, 138.6, 139.1, 170.4 (×2), 171.0 ppm;
HR-FAB MS [M + Na]+ calcd for C51H64NaO14Si calcd 951.3963,
found 951.3961.
Benzoxazolyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzyl-
D-glucopyranosyl)-1-thio-â-D-glucopyranoside (47) was obtained
using method C from 5 and 46 as a colorless syrup in 64% yield
(R/â ) 3/1). Selected analytical data for R-47: Rf ) 0.40 (ethyl
1
acetate-toluene, 1/9, v/v); H NMR δ 3.42-3.52 (m, 4H), 3.66
(dd, 1H, H-6b′), 3.74-3.83 (m, 2H), 3.89 (dd, 1H, J6a′,6b′ ) 9.2
Hz, H-6a′), 4.23-4.34 (m, 2H), 4.39 (m, 1H, J5′,6a′ ) 6.8 Hz, J5′,6b′
) 2.3 Hz, H-5′), 4.43-4.47 (m, 2H), 4.57 (dd, 2H, J2 ) 12.1 Hz,
CH2Ph), 4.70 (d, 1H, J1,2 ) 1.6 Hz, H-1), 4.73-4.77 (m, 2H), 5.64
(dd, 1H, J4′,5′ ) 10.0 Hz, H-4′), 5.70 (dd, 1H, J3′,4′ ) 10.0 Hz,
H-3′), 6.03 (dd, 1H, J2′,3′ ) 9.4 Hz, H-2′), 6.07 (d, 1H, J1′,2′ ) 10.6
Hz, H-1′), 7.01-7.98 (m, 39H, aromatic); 13C NMR δ 66.5, 68.5,
69.6, 70.2, 70.7, 73.4, 73.4, 74.3, 74.7, 75.7, 78.0, 80.1, 82.1, 84.0,
97.1, 110.4, 119.0, 124.4, 124.6, 127.5, 127.6, 127.7, 127.9 (×4),
128.0 (×2), 128.1 (×3), 128.3 (×2), 128.3 (×3), 128.5 (×4), 128.5
(×2), 128.6 (×2), 128.6 (×2), 128.7 (×2), 128.8, 128.9, 129.1,
130.1 (×5), 133.5, 133.7, 138.2, 138.5, 138.9, 139.2, 141.8, 152.2,
161.4, 165.2, 165.5, 165.9; HR-FAB MS [M + Na]+ calcd for
C68H61NNaO14S 1170.3710, found 1170.3724.
2-Trimethylsilylethyl 2-O-(3,4,6-tri-O-acetyl-2-O-benzyl-D-
glucopyranosyl)-3-O-benzyl-4,6-O-benzylidene-â-D-galactopyra-
noside (38) was obtained using method A from 7 and 16 colorless
syrup in 78% yield (R/â ) 3/1). Selected analytical data for R-38:
1
Rf ) 0.51 (ethyl acetate-hexane, 1/1, v/v); H NMR δ -0.40 (s,
9H, Si(CH3)3), 0.99 (m, 2H, CH2TMS), 1.86, 1.93, 1.99 (3 s, 9H,
3 × COCH3), 3.38 (m, 1H, J5,6a ) 2.5 Hz, J5,6b ) 4.5 Hz, H-5),
a
3.50 (m, 1H, -OCH2 ), 3.59 (dd, 1H, J2′,3′ ) 9.6 Hz, H-2′), 3.70
(dd, 1H, J3,4 ) 3.8 Hz, H- 3), 3.77 (dd, 1H, J6a,6b ) 12.8 Hz,
b
Ethyl 6-O-(3,4,6-tri-O-acetyl-2-O-benzyl-R-D-glucopyranosyl)-
2,3,4-tri-O-benzoyl-1-thio-â-D-galactopyranoside (50) was ob-
tained from 7 and 4957 using method B in 98% (R only) as a
colorless syrup. Analytical data for 50: Rf ) 0.51 (ethyl acetate-
hexane, 1/1, v/v); [R]22D 140.0 (c ) 1.0, CHCl3); 1H NMR δ 1.35
(dd, 3H), 2.01, 2.01, 2.18 (3 s, 9H, 3 × COCH3), 2.84 (m, 2H),
3.54-3.65 (m, 2H), 3.74 (s, 2H), 3.86 (dd, 1H, J ) 7.2, J ) 10.4
Hz), 4.04 (dd, 1H, J ) 2.0, J ) 12.4 Hz), 4.17 (m, 1H), 4.24-
4.30 (m, 2H), 4.62 (dd, 2H, J ) 12.5 Hz), 4.77 (d, 1H, J ) 3.5
Hz), 4.85 (d, 1H, J ) 10.0 Hz), 4.97 (dd, 1H, J ) 10.4 Hz), 5.44
(dd, 1H, J ) 9.6 Hz), 5.60 (dd, 1H, J ) 3.3, J ) 10.0 Hz), 5.81
(dd, 1H, J ) 5.0 Hz), 5.90 (d, 1H, J ) 3.3 Hz), 7.20-8.10 (m,
20H); 13C NMR δ 20.8 (×2), 21.0, 24.9, 29.5, 29.6, 29.9, 31.9,
32.1, 54.0, 62.0, 67.3, 67.6, 68.5, 68.7, 69.3, 69.7, 72.0, 73.0, 73.3,
76.6, 76.7, 84.4, 96.9, 128.2, 128.3, 128.5, 128.6, 128.7, 128.9,
129.0, 129.4, 129.9, 130.1, 133.4, 133.5, 133.9, 137.8, 165.6 (×2),
165.8, 169.9, 170.2, 170.8; HR-FAB MS [M + Na]+ calcd for
C48H50NaO16S 937.2717, found 937.2717.
H-6b), 3.87 (dd, 1H, H-6a), 4.00 (m, 1H, -OCH2 ), 4.05 (m, 2H,
H-6a′,6b′), 4.10 (dd, 1H, J2,3 ) 9.4 Hz, H-2), 4.28 (dd, 1H, H-4),
4.38 (d, 1H, J1,2 ) 11.3 Hz, H-1), 4.58 (m, 1H, H-5′), 4.89 (dd,
1H, J4′,5′ ) 10.4 Hz, H-4′), 5.49 (dd, 1H, J3′,4′ ) 9.8, H-3′), 5.78
(d, 1H, J1′,2′ ) 3.6 Hz, H-1′), 7.26-7.56 (m, 15H, aromatic); 13C
NMR δ -1.3, 18.8, 20.8, 21.1, 29.9, 62.0, 66.5, 66.8, 67.1, 68.8,
69.5, 70.8, 71.8, 71.9, 72.6, 72.7, 95.1, 101.4, 102.9, 126.6 (×2),
127.7 (×2), 128.1, 128.2, 128.3 (×2), 128.5 (×2), 128.7 (×4),
129.2, 137.9 (×2), 138.1, 170.0, 170.1, 171.1; HR-FAB MS [M +
Na]+ calcd for C44H56NaO14Si calcd 859.3337, found 859.3351.
Methyl 6-O-(3,4,6-tri-O-acetyl-2-O-benzyl-D-galactopyrano-
syl)-2,3,4-tri-O-benzoyl-â-D-galactopyranoside (39) was obtained
using method B from 8 and 10 in 97% yield (R/â ) 4/1). Analytical
data for R-39: Rf) 0.54 (ethyl acetate-hexanes, 1/1, v/v); 1H NMR
δ 1.96, 1.99, 2.10 (3 s, 9H, 3 × COCH3), 3.59 (s, 3H, OCH3),
3.54 (dd, 1H, H-6b), 3.75 (dd, 1H, J2′,3′ ) 7.6 Hz, H-2′), 3.86 (dd,
1H, J6a,6b ) 10.4 Hz, H-6a), 4.33 (dd, 1H, H-6b′), 4.67 (dd, 1H,
J6a′,6b′ ) 10.7 Hz, H-6a′), 4.21 (m, 1H, J5,6a ) 4.3 Hz, J5,6b ) 2.8
Hz, H-5), 4.31 (dd, 1H, J5′,6a′ ) 4.2 Hz, J5′,6b′ ) 3.1 Hz, H-5′),
4.65 (s, 2H, CH2Ph), 4.69 (d, 1H, J1,2 ) 8.1 Hz, H-1), 4.76 (d, 1H,
Pent-4-enyl O-(3,4,6-tri-O-acetyl-2-O-benzyl-R-D-glucopyra-
nosyl)-(1f6)-O-(2,3,4-tri-O-benzoyl-â-D-galactopyranosyl)-(1f6)-
2,3,4-tri-O-benzyl-â-D-glucopyranoside (51) was prepared from
(56) Nilsson, U.; Ray, A. K.; Magnusson, G. Carbohydr. Res. 1994, 252,
117-136.
(57) Birberg, W.; Lonn, H. Tetrahedron Lett. 1991, 32, 7453-7456.
6954 J. Org. Chem., Vol. 72, No. 18, 2007

S-Benzoxazolyl in Oligosaccharide Synthesis
48 and 50 using method A in 92% yield as a colorless syrup.
Analytical data for 51: Rf ) 0.57 (ethyl acetate-hexane, 1/1, v/v);
[R]22D 98.9 (c ) 1.0, CHCl3); 1H NMR δ 1.61-1.74 (m, 2H), 1.94,
1.97, 1.98 (3 s, 9H, 3 × COCH3), 2.05-2.18 (m, 2H), 3.31-3.46
(m, 4H), 3.51-3.56 (m, 2H), 3.63 (dd, 1H, J ) 6.0, J ) 10.5 Hz),
3.80-3.86 (m, 3H), 3.97-4.12 (m, 3H), 4.22-4.29 (m, 3H), 4.44-
4.67 (m, 6H), 4.78-5.03 (m, 7H), 5.42 (dd, 1H, J ) 9.6 Hz), 5.53
(dd, 1H, J ) 3.5, J ) 10.4 Hz), 5.76-5.84 (m, 2H), 5.87 (dd, 1H,
J ) 3.2 Hz), 7.10-8.15 (m, 35H); 13C NMR δ 20.8, 21.0, 29.1,
29.9, 30.4, 32.1, 62.0, 66.6, 67.8, 68.4, 68.7, 68.8, 69.4, 70.2, 72.0,
72.6, 73.1, 74.9, 75.1, 75.7, 76.6, 77.8, 82.3, 84.7, 97.2, 101.8,
103.7, 115.2, 127.7, 127.9, 128.0, 128.3, 128.5, 128.6, 128.7, 128.9,
129.2, 129.9, 129.9, 130.3, 133.4, 133.8, 137.9, 138.2, 138.6, 138.8,
165.4, 165.6, 165.9, 169.9, 170.7 (×2); HR-FAB MS [M + Na]+
calcd for C78H82NaO22 1393.5196, found 1393.5216.
Ethyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzoyl-â-D-
glucopyranosyl)-1-thio-â-D-galactopyranoside (52) was obtained
using method A from 2 and 4957 in 99% yield. Analytical data for
52 were essentially the same as reported previously.13
Pent-4-enyl O-(2,3,4,6-tetra-O-benzoyl-â-D-glucopyranosyl)-
(1f6)-O-(2,3,4-tri-O-benzoyl-â-D-galactopyranosyl)-(1f6)-3-O-
benzoyl-2-deoxy-2-phthalimido-â-D-glucopyranoside (54) was
prepared from 50 and 51 using method A in 90% yield as a colorless
133.8, 134.3 (×2), 138.0 (×2), 165.3, 165.3, 165.4, 165.6, 165.8,
166.3, 166.5, 166.9, 207.2 (×2); HR-FAB MS [M + Na]+ calcd
for C87H75NaNO25 1556.4526, found 1556.4497.
Methyl O-(2,3,4,6-tetra-O-benzoyl-â-D-glucopyranosyl)-(1f6)-
O-(2,3,4-tri-O-benzoyl-â-D-galactopyranosyl)-(1f6)-O-(3-O-ben-
zoyl-2-deoxy-2-phthalimido-â-D-glucopyranosyl)-2,3,4-tri-O-
benzyl-R-D-glucopyranoside (55) was obtained from 54 and 14
using conventional NIS/TMSOTf activation (see the Supporting
Information) in 73% yield as a colorless syrup. Selected analytical
data for 55: Rf ) 0.5 (ethyl acetate-hexane, 1/1, v/v); [R]22D 26.1
(c ) 1.0, CHCl3); 1H NMR δ 3.06 (s, 3H), 3.13 (m, 1H), 3.28 (dd,
1H, J ) 3.4, 9.6 Hz), 3.34 (dd, 1H, J ) 3.1 Hz), 3.42-3.48 (m,
2H), 3.62-3.77 (m, 4H), 3.87-4.24 (m, 7H), 4.26-4.36 (m, 3H),
4.52 (dd, 1H, J ) 3.2 Hz), 4.56 (dd, 2H, J ) 12.2 Hz), 4.66 (d,
1H, J ) 7.9 Hz), 4.67 (dd, 2H, J ) 10.9 Hz), 5.01 (d, 1H, J ) 7.8
Hz), 5.30 (d, 1H, J ) 8.4 Hz), 5.40 (dd, 1H, J ) 3.5, J ) 10.4
Hz), 5.46 (dd, 1H, J ) 7.9, J ) 9.7 Hz), 5.6 (dd, 1H, J ) 8.4 Hz),
5.66 (dd, 1H, J ) 7.8, J ) 10.4 Hz), 5.72-5.76 (m, 2H), 5.80 (dd,
1H, J ) 9.5 Hz), 6.87-8.01 (m, 59H); 13C NMR δ 29.9, 54.6,
55.3, 62.9, 68.1, 68.3, 69.0, 69.3, 69.4, 69.6, 69.6, 70.1, 70.6, 71.8,
71.9, 72.5, 73.2, 73.6, 74.3, 74.9, 75.3, 75.8, 80.0, 82.0, 98.1, 98.2,
101.4, 102.0, 127.7-139.0 (72 signals), 165.3, 165.3, 165.4, 165.6,
165.8, 166.3, 166.3, 166.9; HR-FAB MS [M + Na]+ calcd for
syrup. Analytical data for 54: Rf ) 0.47 (ethyl acetate-hexane,
C110H97NaNO30 1934.5993, found 1934.5965.
1
1/1, v/v); [R]22 90.1 (c ) 0.6, CHCl3); H NMR δ 1.27 (m,2H,
D
-OCH2CH2CH2), 1.67 (m, 2H, -OCH2CH2CH2), 3.18 (m, 1H,
Acknowledgment. We thank the National Institute of
b
a
OCH2 ), 3.50 (m, 1H, OCH2 ), 3.60 (m, 1H, H-6b), 3.68 (m, 1H,
H-4), 3.71 (m, 1H, H-6a), 3.90 (m, 1H, H-5′), 3.94 (m, 1H, H-6b′),
4.06 (m, 1H, H-6a′), 4.09 (m, 1H, J5′,6a′ ) 3.2 Hz, J5′,6b′ ) 3.2 Hz,
H-5′), 4.33 (dd, 1H, H-6b′), 4.52 (dd, 1H, J6a′,6b′ ) 11.9 Hz, H-6a′),
General Medical Sciences (GM077170) and the University of
MissourisSt. Louis Graduate School Dissertation Fellowship
(to M.N.K.) for financial support of this research; the NSF for
grants to purchase the NMR spectrometer (CHE-9974801) and
the mass spectrometer (CHE-9708640) used in this work; Dr.
R. S. Luo for assistance with 500 MHz 2D NMR experiments;
and Dr. R. E. K. Winter and Mr. J. Kramer for HRMS
determinations.
a
4.57 (m, 1H, ) CH2 ), 4.63 (d, 1H, J1′,2′ ) 7.9 Hz, H-1′), 4.66 (m,
b
1H, dCH2 ), 5.08 (d, 1H, J1′,2′ ) 8.1 Hz, H-1′), 5.23 (d, 1H, J1,2
)
7.7 Hz, H-1), 5.41 (dd, 1H, J3′,4′ ) 9.8 Hz, H-3′), 5.44 (m, 1H,
-CHd), 5.46 (dd, 1H, J2′,3′ ) 9.8 Hz, H-2′), 5.61 (dd, 1H, J4′,5′
)
9.4 Hz, H-4′), 5.70 (dd, 1H, J2′,3′ ) 8.1 Hz, H-2′), 5.75 (m, 1H,
H-4′), 5.77 (dd, 1H, J3,4 ) 9.8 Hz, H-3), 5.81 (dd, 1H, J3′,4′ ) 9.6
Hz, H-3′), 7.10-8.00 (m, 59H, aromatic); 13C NMR δ 28.6, 29.9,
30.0, 31.1, 68.2, 69.0, 69.1, 69.6 (×2), 69.9, 70.8, 71.8, 71.9, 72.5,
73.3, 74.6, 75.0 (×2), 98.1, 101.4, 101.9, 114.8, 123.7 (×2), 128.5
(×14), 128.8, 129.0 (×6), 129.2, 129.4, 129.5, 129.8 (×3), 130.0
(×10), 130.1 (×3), 130.2 (×3), 133.4 (×2), 133.5 (×2), 133.7,
Supporting Information Available: Spectra for all new
compounds and experimental procedures and characterization data
for compounds 42-44, 46, 48, and 53. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO071191S
J. Org. Chem, Vol. 72, No. 18, 2007 6955