Blockwise Approach to Fragments of the O-Specific Polysaccharide of Shigella flexneri Serotype 2a: Convergent Synthesis of A Decasaccharide Representative of a Dimer of the Branched Repeating Unit

Article abstract of DOI:10.1021/jo035125b

The D′A′B′(E′)C′DAB(E)C decasaccharide representative of a dimer of a frame-shifted pentasaccharide repeating unit of the O-specific polysaccharide of Shigella flexneri 2a was synthesized as its methyl glycoside by condensing a pentasaccharide donor (D′A′B′ (E′)C′) and a pentasaccharide acceptor (DAB(E)C-OMe). Several convergent routes to these two building blocks, involving either the AB linkage or the BC linkage as the disconnection site, were evaluated in comparison to the linear strategy. The latter was preferred. It is based on the use of the trichloroacetimidate chemistry. The target branched oligosaccharide was designed to probe the recognition at the molecular level of the natural polysaccharide by protective monoclonal antibodies.

Full text of DOI:10.1021/jo035125b

Block w ise Ap p r oa ch to F r a gm en ts of th e O-Sp ecific
P olysa cch a r id e of Sh igella flexn er i Ser otyp e 2a : Con ver gen t
Syn th esis of a Deca sa cch a r id e Rep r esen ta tive of a Dim er of th e
Br a n ch ed Rep ea tin g Un it1
Fre´de´ric Be´lot,† Karen Wright,†,§ Corina Costachel,†,‡ Armelle Phalipon,‡ and
Laurence A. Mulard*,†
Unite´ de Chimie Organique, URA CNRS 2128, and Unite´ de Pathoge´nie Microbienne Mole´culaire,
INSERM 389, Institut Pasteur, 28 rue du Dr Roux, 75 724 Paris Cedex 15, France
lmulard@pasteur.fr
Received J uly 31, 2003
The D′A′B′(E′)C′DAB(E)C decasaccharide representative of a dimer of a frame-shifted pentasac-
charide repeating unit of the O-specific polysaccharide of Shigella flexneri 2a was synthesized as
its methyl glycoside by condensing a pentasaccharide donor (D′A′B′(E′)C′) and a pentasaccharide
acceptor (DAB(E)C-OMe). Several convergent routes to these two building blocks, involving either
the AB linkage or the BC linkage as the disconnection site, were evaluated in comparison to the
linear strategy. The latter was preferred. It is based on the use of the trichloroacetimidate chemistry.
The target branched oligosaccharide was designed to probe the recognition at the molecular level
of the natural polysaccharide by protective monoclonal antibodies.
In tr od u ction
confer type-specific immunity,6 which points to the O-
specific polysaccharide (O-SP) moiety of the LPS as the
target antigen of the host’s protective immune response
to infection. Besides, data show that significant levels of
preexisting antibodies specific for the O-SP correlate with
a diminished attack rate of shigellosis.7 Furthermore, it
was recently demonstrated in field trials that protein
conjugates of detoxified LPS provided protection to
human volunteers against infections caused by S. sonnei.8
As was particularly emphasized in the case of S. dysen-
teriae type 1, conjugates incorporating oligosaccharide
fragments of the native bacterial polysaccharides may
be even more immunogenic than their counterparts made
of the detoxified LPS.9
Of most concern among the different species of Shigella
is S. flexneri serotype 2a, the prevalent infective agent
responsible for the endemic form of the disease.10 Indeed,
major efforts from different laboratories, including the
development of conventional polysaccharide-protein con-
jugates,11 aim at the development of a vaccine against
the disease associated with this particular serotype. In
parallel, we are developing a program aimed at the
design of chemically defined glycoconjugate vaccines
Shigellosis or bacillary dysentery is a worldwide dis-
ease, occurring in humans only, caused by organisms of
the genus Shigella. Responsible for an estimated 200
million cases annually, Shigella is increasingly resistant
to antimicrobial drugs.2 Shigellosis is a priority target
for vaccine development as defined by the World Health
Organization since this disease is a major cause of
mortality in developing countries, especially among
children under 5 years of age and in the immunocom-
promised population.3 Although no vaccine is yet avail-
able against shigellosis, several programs targeting the
eradication of this bacterial infection are under develop-
ment,2 with emphasis on vaccination strategies involving
either live attenuated strains of Shigella4 or acellular
vaccines based on lipopolysaccharide (LPS) antigens and
derivatives thereof.5 Of particular interest in the later
approach is the design of glycoconjugate vaccines based
on the use of detoxified LPS. Indeed, there is evidence
that natural and experimental infections with Shigella
* Corresponding author.
† Unite´ de Chimie Organique.
§ Present address: SIRCOB, Universite´ de Versailles, 45 avenue
des Etats-Unis, 78 035 Versailles Cedex, France.
(6) DuPont, H. L.; Hornick, R. B.; Dawkins, A. T.; Synder, M. J .;
Formal, S. B. J . Infect. Dis. 1969, 119, 296-299.
(7) Cohen, D.; Green, M. S.; Block, C.; Slepon, R.; Ofek, I. J . Clin.
Microbiol. 1991, 29, 386-389.
‡ Unite´ de Pathoge´nie Microbienne Mole´culaire.
(1) Part 10 of the series Synthesis of ligands related to the O-specific
polysaccharides of Shigella flexneri serotype 2a and Shigella flexneri
serotype 5a. For part 9, see ref 19.
(2) WHO Weekly Epidemiol. Rec. 1997, 72, 73-79.
(3) Kotloff, K. L.; Winickoff, J . P.; Ivanoff, B.; Clemens, J . D.;
Swerdlow, D. L.; Sansonetti, P. J .; Adak, G. K.; Levine, M. M. Bull.
WHO 1999, 77, 651-666.
(4) Coster, T. S.; Hoge, C. W.; Verg, L. L. v. d.; Hartman, A. B.; Oaks,
E. V.; Venkatesan, M. M.; Cohen, D.; Robin, G.; Fontaine-Thompson,
A.; Sansonetti, P. J .; Hale, T. L. Infect. Immun. 1999, 67, 3437-3443.
(5) Fries, L. F.; Montemarano, A. D.; Mallett, C. P.; Taylor, D. N.;
Hale, T. L.; Lowell, G. H. Infect. Immun. 2001, 69, 4545-4553.
(8) Cohen, D.; Ashkenazi, S.; Green, M. S.; Gdalevich, M.; Robin,
G.; Slepon, R.; Yavzori, M.; Orr, N.; Block, C.; Ashkenazi, I.; Shemer,
J .; Taylor, D. N.; Hale, T. L.; Sadoff, J . C.; Pavliovka, D.; Schneerson,
R.; Robbins, J . B. The Lancet 1997, 349, 155-159.
(9) Pozsgay, V.; Chu, C.; Panell, L.; Wolfe, J .; Robbins, J . B.;
Schneerson, R. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 5194-5197.
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(11) Passwell, J . H.; Harlev, E.; Ashkenazi, S.; Chu, C.; Miron, D.;
Ramon, R.; Farzan, N.; Shiloach, J .; Bryla, D. A.; Majadly, F.; Roberson,
R.; Robbins, J . B.; Schneerson, R. Infect. Immun. 2001, 69, 1351-1357.
10.1021/jo035125b CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/23/2004
1060
J . Org. Chem. 2004, 69, 1060-1074

Convergent Synthesis of a Branched Decasaccharide
based on the use of synthetic fragments of the O-SP of
S. flexneri 2a. To achieve this goal, we adopted a rational
approach, involving a preliminary study of the interaction
between the bacterial O-SP and homologous protective
monoclonal antibodies. The O-SP of S. flexneri 2a is a
and a pentasaccharide donor bearing a 2-O-acyl protect-
ing group at the reducing residue (C) in order to direct
glycosylation toward the desired stereochemistry. De-
pending on the nature of the 2-N-acyl group in residue
D, the latter could derive from the allyl glycosides 4 or
5.
Besides, bearing in mind that the major drawbacks of
the linear synthesis of pentasaccharide 2 reported so far17
dealt with the selective deblocking of key hydroxyl groups
to allow further chain elongation, we describe herein
various attempts at a convergent synthesis of the fully
protected DAB(E)C pentasaccharide as its methyl (2, 3)
or allyl (4, 5) glycosides. Precedents concerning a related
serotype of S. flexneri have indicated that disconnection
at the D-A linkage should be avoided.21,22 To our
knowledge, disconnection at the B-C linkage was never
attempted in the series. However, disconnection at the
A-B linkage, based on the use of a combination of a
bromide disaccharide donor and Hg(CN)2/HgBr2 as the
promoter, was reported once.20 In the latter case concern-
ing the synthesis of the linear DABC tetrasaccharide,
the condensation of two disaccharide building blocks was
found more effective than the stepwise strategy. Both
routes were considered in the following study. The nature
of the repeating unit I indicated that any blockwise
synthesis involving such linkages would rely on donors
lacking any participating group at position 2 of the
reducing residue, thus the relevance of this strategy may
be questioned. Nevertheless, although â-glycoside forma-
tion was observed occasionally,23-25 the good R-stereose-
lectivity reported on several occasions in the literature
for glycosylation reactions based on mannobiosyl donors26
and derivatives such as perosamine analogues27,28 or
rhamnopyranosyl donors that were either glycosylated
at C-220,29 or blocked at this position with a nonpartici-
pating group30,31 encouraged the evaluation of the above-
mentioned block strategies. To follow up the work
developed thus far in the S. flexneri 2a series, emphasis
was placed on the use of the trichloroacetimidate (TCA)
chemistry.32
heteropolysaccharide defined by its biological repeating
unit, the AB(E)CD sequence,12,13 corresponding to a
frame-shifted pentasaccharide I. It features a linear
tetrasaccharide backbone, which is common to all S.
flexneri O-antigens and comprises a N-acetyl glucosamine
and three rhamnose residues, together with an R-D-
glucopyranose residue branched at position 4 of one of
the rhamnoses. Besides the known methyl glycoside of
the EC disaccharide,14,15 a set ofdi-topentasaccharides16-18
and more recently an octasaccharide19 representative of
fragments of S. flexneri 2a O-SP have been synthesized.
The use of these compounds as molecular probes for
mapping at the molecular level the binding characteris-
tics of a set of protective antibodies against S. flexneri
2a infection indicated that access to larger oligosaccha-
rides would help the characterization of the carbohydrate
antigenic determinants. For this purpose, methodologies
allowing a straightforward access to S. flexneri 2a oli-
gosaccharides of larger size are under study in this
laboratory. We now report the synthesis of the first
decasaccharide in the series, namely the D′A′B′(E′)-
C′DAB(E)C fragment, which was prepared as its methyl
glycoside (1).
Resu lts a n d Discu ssion
Considering its dimeric nature, a convergent synthetic
strategy to the target 1 was considered. Indeed, retrosyn-
thetic analysis, supported by previous work in the
field,19-22 indicated that disconnections at the C-D
linkage, thus based on two DAB(E)C branched pen-
tasaccharides I, would be the most advantageous (Scheme
1). Such a strategy would involve a pentasaccharide
acceptor easily derived from the known methyl glycoside
217 or from the corresponding N-acetylated analogue 3
Str a tegy Ba sed on th e Discon n ection a t th e A-B
Lin k a ge (Sch em e 1, r ou te a ). Such a strategy involves
the coupling of suitable DA donors to an appropriate B-
(E)C acceptor. Taking into account the glycosylation
chemistry, two sets of disaccharide building blocks (6, 7,
8), easily obtained from known monosaccharide precur-
sors which were readily available by standard protecting
group/activation strategies, were selected (Scheme 1).
(12) Simmons, D. A. R. Bacteriol. Rev. 1971, 35, 117-148.
(13) Lindberg, A. A.; Karnell, A.; Weintraub, A. Rev. Infect. Dis.
1991, 13, S279-S284.
(14) Berry, J . M.; Dutton, G. G. S. Can. J . Chem. 1974, 54, 681-
(23) Sadozai, K. H.; Nukada, T.; Ito, Y.; Nakahara, Y.; Ogawa, T.
Carbohydr. Res. 1986, 157, 101-123.
683.
(15) Lipkind, G. M.; Shashkov, A. S.; Nikolaev, A. V.; Mamyan, S.
S.; Kochetkov, N. K. Bioorg. Khim. 1987, 13, 1081-1092.
(16) Mulard, L. A.; Costachel, C.; Sansonetti, P. J . J . Carbohydr.
Chem. 2000, 19, 849-877.
(24) Srivastava, O. P.; Hindsgaul, O. Can. J . Chem. 1986, 64, 2324-
2330.
(25) Soliveri, G.; Bertolotti, A.; Panza, L.; Poletti, L.; J ones, C.; Lay,
L. J . Chem. Soc., Perkin Trans 1 2002, 2174-2181.
(26) Ogawa, T.; Yamamoto, H. Carbohydr. Res. 1982, 104, 271-283.
(27) Peters, T.; Bundle, D. R. Can. J . Chem. 1989, 67, 491-496.
(28) Lei, P. S.; Ogawa, Y.; Kovac, P. Carbohydr. Res. 1996, 281, 47-
60.
(17) Costachel, C.; Sansonetti, P. J .; Mulard, L. A. J . Carbohydr.
Chem. 2000, 19, 1131-1150.
(18) Segat, F.; Mulard, L. A. Tetrahedron: Asymmetry 2002, 13,
2211-2222.
(19) Be´lot, F.; Costachel, C.; Wright, K.; Phalipon, A.; Mulard, L.
A. Tetrahedron Lett. 2002, 43, 8215-8218.
(29) Reimer, K. B.; Harris, S. L.; Varma, V.; Pinto, B. M. Carbohydr.
Res. 1992, 228, 399-414.
(20) Kochetkov, N. K.; Byramova, N. E.; Tsvetkov, Y. E.; Backi-
novsky, L. V. Tetrahedron 1985, 41, 3363-3375.
(21) Pinto, B. M.; Reimer, K. B.; Morissette, D. G.; Bundle, D. R. J .
Org. Chem. 1989, 54, 2650-2656.
(30) Varga, Z.; Bajza, I.; Batta, G.; Lipta´k, A. Tetrahedron Lett. 2001,
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(31) Varga, Z.; Bajza, I.; Batta, G.; Lipta´k, A. Tetrahadron Lett.
2002, 43, 3145-3148.
(22) Pinto, B. M.; Reimer, K. B.; Morissette, D. G.; Bundle, D. R. J .
Chem. Soc., Perkin Trans. 1 1990, 293-299.
(32) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21-123.
J . Org. Chem, Vol. 69, No. 4, 2004 1061

Be´lot et al.
SCHEME 1a
a
Retrosynthetic analysis of the target decasaccharide 1.
Thus, condensation of the allyl rhamnopyranoside 14,33
as precursor to residue A, with the glucosaminyl trichlo-
roacetimidate 16,34 as precursor to residue D, was
performed in the presence of a catalytic amount of
TMSOTf to give the fully protected disaccharide 17 in
99% yield (Scheme 2). Selective deallylation of 17 pro-
ceeded in two steps involving (i) iridium(I)-catalyzed
isomerization of the allyl glycoside into the corresponding
1-O-propenyl glycoside35 and (ii) hydrolysis of the latter.36
The resulting hemiacetal 18 (81%) was converted into
the trichloroacetimidate 6 (78%) by treatment with
trichloroacetonitrile in the presence of a catalytic amount
of DBU. Knowing from previous experience that conver-
sion of the trichloroacetamide moiety at position 2 of
residue D (2D-N-trichloroacetyl moiety) into the required
2D-N-acetyl group could be somewhat low-yielding, we
took advantage of the blockwise approach to perform the
above-mentioned transformation at an early stage in the
synthesis. Thus, the disaccharide intermediate 17 was
converted to the corresponding 19 (90%) upon overnight
treatment with a saturated ammonia methanolic solution
and subsequent peracetylation. Conversion of 19 into the
hemiacetal 20 (69%), and next into the required trichlo-
roacetimidate donor 7 (86%), followed the procedure
described above for the preparation of 6 from 17. Where
glycosylation is concerned, the bifunctional role of thiogly-
cosides as protected acceptors and masked donors is
highly appreciated.37 Thus, the thiophenyl disaccharide
8 was considered as a possible alternative to the use of
the more reactive trichloroacetimidates 6 and 7. It was
synthesized in 97% yield by condensing the known
thiophenyl rhamnopyranoside 1538 and 16 in the pres-
ence of a catalytic amount of TMSOTf (Scheme 2). To
fulfill the requirements of the synthesis of 1, two different
trisaccharide building blocks were used, namely either
the known methyl glycoside 917 or the corresponding allyl
glycoside 10, obtained from the known 2B-O-acetylated
trisaccharide 42 (see below and Scheme 5).18 Condensa-
tion of the trisaccharide acceptor 9 and the trichloroace-
timidate donor 6 was attempted under various conditions
of solvent, temperature, and promoter. The R-linked
condensation product, i.e. the known pentasaccharide 2,17
was at best isolated in 41% yield providing that the
glycosylation reaction was run in acetonitrile in the
presence of a catalytic amount of TMSOTf, following the
(33) Westerduin, P.; Haan, P. E. d.; Dees, M. J .; Boom, J . H. v.
Carbohydr. Res. 1988, 180, 195-205.
(34) Blatter, G.; Beau, J .-M.; J acquinet, J .-C. Carbohydr. Res. 1994,
260, 189-202.
(37) Oscarson, S. In Carbohydrates in chemistry and biology. Part
1: Chemistry of saccharides; Ernst, B., Hart, G. W., Sinay¨, P., Eds.;
Wiley-VCH: Weinheim, Germany, 2000; Vol. 1, pp 93-116.
(38) Lau, R.; Schuele, G.; Schwaneberg, U.; Ziegler, T. Liebigs Ann.
Org. Bioorg. Chem. 1995, 10, 1745-1754.
(35) Oltvoort, J . J .; van Boeckel, C. A. A.; der Koning, J . H.; van
Boom, J . Synthesis 1981, 305-308.
(36) Gigg, R.; Warren, C. D. J . Chem. Soc. C 1968, 1903-1911.
1062 J . Org. Chem., Vol. 69, No. 4, 2004

Convergent Synthesis of a Branched Decasaccharide
SCHEME 2a
the good R-selectivity, but poor yields, of the condensation
of the various DA donors with the B(E)C acceptors 9 and
10 might result from the poor nucleophilicity of the axial
hydroxyl at position 2B. Thus, we next turned to the 3C-
OH as a possible elongation site in the design of a block
synthesis of pentasaccharide 5. Considering such a
disconnection approach suggests the use of a DAB
trisaccharide donor for coupling to an EC disaccharide
acceptor. As the target pentasaccharide should serve as
an appropriate donor in the construction of 1, we rea-
soned that an acyl participating group had to be present
at its position 2C. Thus, two 2C-O-acylated EC building
blocks, 11 or 12, were considered. To avoid any unneces-
sary deprotection step at the pentasaccharide level, the
trisaccharide 13, bearing an acetamido functionality at
position 2D, was selected as the donor. Indeed, as it
involves the less readily available EC structure in fewer
synthetic steps and does not rely on selective deprotection
at the 2A position, this path was found particularly
attractive. Again, it relies on the use of appropriately
functionalized known monosaccharide intermediates
(Scheme 3).
The known key di-rhamnoside core structure 2241 was
formed by glycosylation of the allyl rhamnoside 14 with
the trichloroacetimidate donor 2142 in the presence of a
catalytic amount of TMSOTf. It should be pointed out
that using diethyl ether as the solvent, the isolated yield
of 22 was 92%, which compares favorably with yields
obtained previously, 60% and 76.2%,41 when running the
reaction in dichloromethane (DCM) under promotion by
TMSOTf or BF3‚OEt2, respectively. Sodium methoxide
promoted de-O-acetylation afforded the 2A-O-unprotected
acceptor 2321 in 93% yield.
a
Reagents and conditions: (a) cat. TMSOTf, anhydrous DCM,
-
0.5h,0°C,97%(8),99%(17);(b)(i)cat.[Ir(COD){PCH3(C6H5)2}2]+PF6
,
THF, rt, 20 h, (ii) HgO, HgCl2, acetone/water, rt, 2 h, 81% (18),
69% (20); (c) CCl3CN, DBU, DCM, 0 °C, 1 h, 78% (6), 86% (7); (d)
(i) NH3, MeOH, 20 h, 0 °C, (ii) Ac2O, MeOH, (iii) Ac2O, Py, 90%;
(e) cat. TMSOTf, CH3CN, 0 °C, 41% (2); (f) cat. TfOH, NIS, Et2O,
1,2-DCE, 0 °C, 10% (4).
As shown previously in the construction of the DA
intermediate 17, the N-trichloroacetyl trichloroacetimi-
date 16 appears to be a highly suitable precursor to
residue D when involved in the formation of the â-GlcNAc
linkage at the poorly reactive 2A position. Indeed, reaction
of 16 with the acceptor 23 in 1,2-dichloroethane (1,2-
DCE) in the presence of TMSOTf went smoothly and gave
the trisaccharide 25 in 96% yield. However, conversion
of the N-trichloroacetyl group to the N-acetyl derivative
27 was rather less successful as the desired trisaccharide
was obtained in only 42% yield when treated under
conditions that had previously been used in the case of a
related oligosaccharide (sodium methoxide, Et3N, fol-
lowed by re-N,O-acetylation).17 This result led us to
reconsider the protection pattern of the glucosamine
donor. The N-tetrachlorophthalimide group has been
proposed as an alternative to overcome problems associ-
ated with the widely spread phthalimido procedure when
introducing a 2-acetamido-2-deoxy-â-D-glucopyranosidic
linkage.43 Thus, the N-tetrachlorophthalimide trichloro-
acetimidate donor 24 was selected as an alternative. It
was prepared as described from commercially available
D-glucosamine,44 apart from the final imidate formation
step, where we found the use of potassium carbonate as
inverted procedure protocol,39,40 to minimize degradation
of the donor. Although the R-selectivity of the glycosyla-
tion reaction was good, yields of pentasaccharide re-
mained low, and as anticipated, use of the alternate
trichloroacetimidate donor 7 to give 3 did not result in
any improvement (not described). Rearrangement of the
activated donor into the corresponding inert trichloroac-
etamide was observed previously in glycosylation reac-
tions based on trichloroacetimidate donors lacking a
participating group at position 2 of the reducing residue.23
Although the expected side product was not isolated in
any of the attempted glycosylation with 6 or 7, it was
anticipated that the use of an alternate glycosylation
chemistry would prevent such side reaction, and possibly
favor the condensation. However, reaction of thiophenyl
donor 8 and acceptor 10 in the presence of N-iodosuc-
cinimide and catalytic triflic acid did not prove any better
as it resulted in mixtures of products from which the
target 4 was isolated in very low yield, 10% at best. This
strategy was thus not considered any further.
(41) Zhang, J .; Mao, J . M.; Chen, H. M.; Cai, M. S. Tetrahedron:
Asymmetry 1994, 5, 2283-2290.
Str a tegy Ba sed on th e Discon n ection a t th e B-C
Lin k a ge (Sch em e 1, r ou te b). It was hypothesized that
(42) Castro-Palomino, J . C.; Rensoli, M. H.; Bencomo, V. V. J .
Carbohydr. Chem. 1996, 15, 137-146.
(39) Schmidt, R. R.; Toepfer, A. Tetrahedron Lett. 1991, 32, 3353-
3356.
(40) Bommer, R.; Kinzy, W.; Schmidt, R. R. Liebigs Ann. Chem.
1991, 425-433.
(43) Debenham, J . S.; Madsen, R.; Roberts, C.; Fraser-Reid, B. J .
Am. Chem. Soc. 1995, 117, 3302-3303.
(44) Castro-Palomino, J . C.; Schmidt, R. R. Tetrahedron Lett. 1995,
36, 5343-5346.
J . Org. Chem, Vol. 69, No. 4, 2004 1063

Be´lot et al.
SCHEME 3a
a
Reagents and conditions: (a) cat. TMSOTf, anhydrous Et2O, 3 h, -55 to -20 °C, 92%; (b) MeONa, MeOH, 3 h, rt, 93%; (c) cat.
TMSOTf, 4 Å molecular sieves, 1,2-DCE, 3 h, -20 to 0 °C, 96%; (d) cat. TMSOTf, anhydrous Et2O, 4 h, 0 °C to rt, 65%; (e) (i) MeONa,
-
MeOH, Et3N, rt, 18 h, (ii) Ac2O, 0.5 h, 0 °C to rt, 45%; (f) Py, Ac2O, 18 h, 0 °C to rt, 94%; (g) (i) cat. [Ir(COD){PCH3(C6H5)2}2]+PF6
,
THF, rt, 20 h, (ii) HgO, HgCl2, acetone/water, rt, 2 h, 83%; (h) CCl3CN, DBU, DCM, 0 °C, 40 min, 94%; (i) (i) ethylenediamine, THF,
EtOH, 55 °C, 4 h, (ii) Ac2O, rt, 1.5 h, (iii) Py, Ac2O, 0 °C, overnight, 68%; (j) (i) PhC(OMe)3, CSA, DCM, (ii) 50% aq TFA, DCM, 87%; (k)
(i) MeC(OMe)3, CSA, DCM, (ii) 50% aq TFA, DCM, 90%; (l) BF3‚Et2O, anhydrous Et2O, 4 Å molecular sieves, 0 °C to rt, 18 h, 44%.
base to be more satisfactory than DBU. Glycosylation of
23 with 24 in the presence of TMSOTf resulted in the
trisaccharide 28 in 65% yield. The tetrachlorophthaloyl
group was then removed by the action of ethylenedi-
amine, and subsequent re-N,O-acetylation gave the
trisaccharide 27 in 68% yield. The latter was next
converted into the donor 13 in two steps, analogous to
those described for the preparation of 6 from 17. Indeed,
de-O-allylation of 27 cleanly gave the hemiacetal 29
(83%), which was then activated into the required
trichloroacetimidate (94%). It is worth mentioning that
although they involve a different D precursor, both
strategies give access to the intermediate 27 in closely
related yields, 40 and 42%, respectively.
Initial attempts to form the pentasaccharide 5 from
13 and the previously described acceptor 1118 in the
presence of TMSOTf as promoter were rather unsuccess-
ful, resulting in at best 17% of the desired product,
accompanied by decomposition of the donor into the
hemiacetal 29 (75%). By using BF3‚OEt2 as the promoter
in place of TMSOTf, reaction of 11 with 13 at rt provided
5 in 44% yield, with the acceptor 11 and hemiacetal 29
also recovered in 54% and 29% yield, respectively. We
considered that the poor reactivity of the acceptor was
responsible for these results, since the 13C NMR spectrum
of 5, showing several broaden signals (notably C-1B, as
well as most certainly C-3C and C-4C), suggests restricted
conformational flexibility around position 3C. For that
matter, the 2C-O-acetylated disaccharide 12 was consid-
ered as an alternate acceptor. Analogously to the prepa-
ration of 11, it was obtained from the known diol 30
through regioselective opening of the intermediate ortho
ester. However, coupling of the potentially less hindered
acceptor 12 and the trisaccharide donor 13 resulted, at
best, in the isolation of the condensation product 31 in
42% yield (not described).
The modest yield of 5 and 31 obtained by this route
made the alternative reaction path (Scheme 4) worth
investigating, despite the more numerous synthetic steps
required. Indeed, it was found rather appealing when
evaluated independently in a closely related series (un-
published results). By this route, a tetrasaccharide
acceptor can be formed from two disaccharide building
blocks (EC and AB), and coupled with an appropriate
monosaccharide donor as precursor to D. Considering
that selective deprotection of the 2A hydroxyl group would
occur in the course of the synthesis, glycosylation at-
tempts were limited to the 2-O-benzoylated acceptor 11.
The disaccharide donor necessary for this path could be
derived from the building block 23, already in hand. The
choice of temporary protecting group at position 2A was
determined by our experience of the stepwise synthesis
of the corresponding methyl pentasaccharide,17 where we
noted that an acetate group at this position may not be
fully orthogonal to the benzoate located at position 2C.
The chosen group had also to support removal of the
anomeric allyl group and the subsequent conversion to
the trichloroacetimidate. At first, a chloroacetate group
was anticipated to fulfill these requirements. Thus, the
disaccharide 23 was treated with chloroacetic anhydride
and pyridine to give the derivative 32 (57%). Anomeric
deprotection to give the hemiacetal 33 (84%) and subse-
1064 J . Org. Chem., Vol. 69, No. 4, 2004

Convergent Synthesis of a Branched Decasaccharide
SCHEME 4a
target 4. Indeed, when put together with our previous
work, such as the synthesis of tetrasaccharide 41 (95%)17
or that of trisaccharide 42 (97%),18 all the above-described
attempted couplings outlined the loss of efficiency of
glycosylation reactions involving rhamnopyranosyl do-
nors glycosylated at position 2 in comparison to those
involving the corresponding acetylated donor. Thus,
matching the linear strategy of the methyl pentasaccha-
ride 2 described previously,17 a synthesis of 4, based on
donors bearing a participating group at O-2, was de-
signed. Three key building blocks were selected. These
were the readily accessible EC disaccharide acceptor 11
benzoylated at C-2 as required for the final condensation
step leading to the fully protected decasaccharide inter-
mediate; the rhamnopyranosyl trichloroacetimidate 21,
which serves as a precursor to residues A and B, and
bears both a temporary and participating group at
position 2; and the trichloroacetamide glucosaminyl donor
16 as a precursor to residue D. As stated above, coupling
of 11 and 21 gave 42 in high yield. As observed in the
methyl glycoside series,17 de-O-acetylation with MeONa
or methanolic HCl was poorly selective. Although guani-
dine/guanidinium nitrate was proposed as a mild and
selective O-deacetylation reagent compatible with the
presence of benzoyl protecting groups,45 none of the
conditions tested prevented partial debenzoylation lead-
ing to diol 43, as easily confirmed from NMR analysis
(not described). The required alcohol 10 was readily
obtained in an acceptable yield of 84% by a 4-day acid-
catalyzed methanolysis, using HBF4 in diethyl ether/
methanol,17,46 of the fully protected intermediate 42.
Repeating this two-step process with 10 as the acceptor
and 21 as the donor resulted first in the intermediate
44 (90%) and next in the tetrasaccharide acceptor 40
(84%). Glycosylation of the latter with 16 gave the fully
protected pentasaccharide 4 in high yield (98%), thus
confirming that the combination of the trichloroacetamide
participating group and the trichloroacetimidate activa-
tion mode in 16 results in a potent donor to be used as a
precursor to residue D in the S. flexneri series, where
low-reactive glycosyl acceptors are concerned. Following
the above-described procedure, selective anomeric depro-
tection of 4 furnished the hemiacetal 45, which was
smoothly converted to the trichloroacetimidate donor 46
(66% from 4). From these data, the linear synthesis of 4,
truly benefiting from the use of 21 as a common precursor
to residues A and B, appears as a reasonable alternative
to the block syntheses which were evaluated in parallel.
a
Reagents and conditions: (a) ClAc2O, Py, 0 °C to rt, overnight,
57%; (b) pMeOBnCl, NaH, DMF, rt, overnight, 97%; (c) (i) cat.
[Ir(COD){PCH3(C6H5)2}2]+PF6-, THF, rt, 20 h, (ii) HgO, HgCl2,
acetone/water, rt, 2 h, 84% (33), 73% (36); (d) CCl3CN, DBU, DCM,
0 °C, 1 h, 83% (34), 82% (37); (e) cat. TMSOTf, anhydrous Et2O,
-60 °C to rt, overnight, 22% (38), 44% (39).
quent trichloroacetimidate activation of the latter into
the donor 34 (83%) were performed in the same way as
before. Coupling of 11 with 34, carried out in the presence
of TMSOTf at -40 °C, yielded a complex mixture of
products. When the temperature was lowered to -60 °C,
the condensation product 38 could be isolated in 22%
yield. Alternative donor protection was attempted. Treat-
ment of 23 with p-methoxybenzyl chloride and sodium
hydride gave the fully protected derivative 35 (97%),
which was cleanly converted into the trichloroacetimidate
donor 37 (82%) in two steps involving the hemiacetal
intermediate 36 (73%). Glycosylation of 11 with 37 in the
presence of TMSOTf at -40 °C gave the desired tetrasac-
charide 39 in 44% yield. When the temperature was
lowered to -60 °C, the yield of 39 fell to 34% and a second
major product 40 (21%) was observed in the mixture.
Indeed, examination of the NMR spectra of this product
revealed that the pMeOBn group had been lost. The
R-stereoselectivity of the glycosylation was ascertained
from the observation that 40 was the acceptor required
for the next step. Consequently, the estimated yield of
condensation was brought to 55%. Nevertheless, the
overall outcome of this blockwise strategy did not match
our expectations, and this route was abandoned.
Syn th esis of th e Tar get Decasacch ar ide 1 (Sch em e
6). Having a pentasaccharide donor in hand, focus was
next placed on the synthesis of an appropriate pentasac-
charide acceptor. In our recent description of the conver-
gent synthesis of the B′(E′)C′DAB(E)C octasaccharide,19
the pentasaccharide 48, bearing a 4D,6D-O-isopropylidene
protecting group, was found a most convenient acceptor,
which encouraged its selection in the present work.
Briefly, 48 was prepared in two steps from the known 2.
Thus, mild transesterification of 2 under Zemple´n condi-
tions allowed the selective removal of the acetyl groups
to give triol 47, which was converted to the required
Lin ea r Str a tegy to th e F u lly P r otected P en ta sa c-
ch a r id e 4 (Sch em e 5). As preliminary studies have
demonstrated, rapid access to suitable building blocks
allowing the synthesis of higher order oligosaccharides
representative of fragments of the O-SP of S. flexneri
2a remains a challenge. Major conclusions drawn from
our studies favor the design of a linear synthesis of the
(45) Ellervik, U.; Magnusson, G. Tetrahedron Lett. 1997, 38, 1627-
1628.
(46) Pozsgay, V.; Coxon, B. Carbohydr. Res. 1994, 257, 189-215.
J . Org. Chem, Vol. 69, No. 4, 2004 1065

Be´lot et al.
SCHEME 5a
a
Reagents and conditions: (a) cat. TMSOTf, anhydrous Et2O, -50 °C to rt, overnight, 97% (42), 90% (44); (b) HBF4/Et2O, MeOH, rt,
4 days, 84% (10), 84% (40); (c) guanidine, DCM, rt; (d) cat. TMSOTf, anhydrous DCM, 4 Å molecular sieves, 0 °C to rt, 3 h, 98%; (e) (i)
cat. [Ir(COD){PCH3(C6H5)2}2]+PF6-, THF, rt, 20 h, (ii) HgO, HgCl2, acetone/water, rt, 2 h; (f) CCl3CN, DBU, DCM, 0 °C, 1 h, 66% (2
steps).
SCHEME 6a
a
Reagents and conditions: (a) MeONa, MeOH, rt, 0.5 h; (b) 2-methoxypropene, CSA, DMF, 72% (2 steps); (c) cat. TfOH, anhydrous
1,2-DCE, 4 Å molecular sieves, -35 °C to -10 °C, 2.5 h; (d) TFA, water/DCM, 0 °C, 3 h, 72% (2 steps); (e) MeONa, MeOH, DCM, 55 °C;
(f) (i) H2, Pd/C, EtOH, EtOAc, 1 M HCl, rt, 72 h, (ii) H2, Pd/C, MeOH, Et3N, rt, 24 h; (g) MeONa, MeOH, DCM, 55 °C, overnight, 37% (3
steps).
acceptor 48 (72% from 2) upon subsequent treatment
with 2-methoxypropene. Relying on previous optimization
of the glycosylation step,19 the condensation of 48 and
46 was performed in the presence of a catalytic amount
of triflic acid. However, probably due to the closely related
nature of the donor and acceptor, the reaction resulted
in an inseparable mixture of the fully protected 49 and
the hemiacetal 45 resulting from partial hydrolysis of the
donor. Most conveniently, acidic hydrolysis of the mix-
ture, allowing the selective removal of the isopropylidene
group in 49, gave the intermediate diol 50 in a satisfac-
tory yield of 72% for the two steps. According to the
1066 J . Org. Chem., Vol. 69, No. 4, 2004

Convergent Synthesis of a Branched Decasaccharide
solution was cooled at 0 °C, Me3SiOTf (28 µL) was added
dropwise and the mixture was stirred for 0.5 h. Triethylamine
(60 µL) was added and the mixture was concentrated. The
residue was eluted from a column of silica gel with 4:1
cyclohexane-EtOAc to give 8 (227 mg, 97%) as a colorless
deprotection strategy used for the preparation of the
closely related octasaccharide,19 diol 50 was engaged in
a controlled de-O-acylation process upon treatment with
hot methanolic sodium methoxide. However, partial
cleavage of the trichloroacetyl moiety, leading to an
inseparable mixture, was observed, which prevented
further use of this strategy. Indeed, it was assumed that
besides being isolated and therefore resistant to Zemple´n
transacetylation conditions,31,47 the 2C-O-benzoyl groups
were most probably highly hindered, which contributed
to their slow deprotection. Alternatively, 50 was submit-
ted to an efficient two-step in-house process involving,
first, hydrogenolysis under acidic conditions which al-
lowed the removal of the benzyl groups and, second, basic
hydrochlorination that resulted in the conversion of the
N-trichloroacetyl groups into the required N-acetyl ones,
thus affording 52. Subsequent transesterification gave
the final target 1 in 37% yield from 50.
1
foam: [R]D -63 (c 1.0, CHCl3); H NMR (CDCl3) δ 7.40-7.10
(m, 15H, Ph), 6.73 (d, 1H, J 2,NH ) 8.5 Hz, NHD), 5.47 (d, 1H,
J 1,2 ) 1.2 Hz, H-1A), 5.07 (pt, 1H, J 2,3 ) J 3,4 ) 10.0 Hz, H-3D),
4.99 (pt, 1H, J 4,5 ) 10.0 Hz, H-4D), 4.80-4.55 (m, 4H, CH2Ph),
4.52 (d, 1H, J 1,2 ) 8.2 Hz, H-1D), 4.13-3.95 (m, 2H, J 5,6 ) 5.3
Hz, J 6a,6b ) 12.2 Hz, H-6aD, 6bD), 4.10 (dq, 1H, J 4,5 ) 9.5 Hz,
J 5,6 ) 6.1 Hz, H-5A), 4.00 (dd, 1H, J 2,3 ) 3.0 Hz, H-2A), 3.99
(m, 1H, H-2D), 3.77 (dd, 1H, J 3,4 ) 9.4 Hz, H-3A), 3.50 (m, 1H,
H-5D), 3.39 (dd, 1H, H-4A), 1.95, 1.93, 1.90 (3s, 9H, OAc), 1.23
(d, 3H, H-6A); 13C NMR (CDCl3) δ 171.1, 170.9, 169.6, 162.1
(CdO), 138.5-127.2 (Ph), 102.1 (C-1D), 92.7 (CCl3), 87.4 (C-
1A), 81.3 (C-4A), 80.5 (C-3A), 79.1 (C-2A), 76.4, 74.1 (2C, CH2-
Ph), 72.4 (C-5D), 72.4 (C-3D), 69.8 (C-5A), 68.7 (C-4D), 62.3 (C-
6D), 56.2 (C-2D), 21.0, 20.9, 20.8 (3C, OAc), 18.1 (C-6A). FAB-
MS for C40H44Cl3NO12S (M, 867), m/z 890 [M + Na]+. Anal.
Calcd for C40H44Cl3NO12S: C, 55.27; H, 5.10; N, 1.61. Found:
C, 55.16; H, 5.18; N, 1.68.
Con clu sion
Allyl (3,4,6-Tr i-O-a cetyl-2-d eoxy-2-tr ich lor oa ceta m id o-
â-D-glu copyr an osyl)-(1f2)-3,4-di-O-ben zyl-r-L-r h am n opy-
r a n osid e (17). A mixture of alcohol 1433 (1.86 g, 4.86 mmol)
and imidate 16 (3.85 g, 6.47 mmol) in anhydrous CH3CN (80
mL) was stirred for 15 min under dry Ar. After the solution
was cooled at 0 °C, Me3SiOTf (46 µL) was added dropwise and
the mixture was stirred for 0.5 h. Triethylamine (150 µL) was
added, and the mixture was concentrated. The residue was
eluted from a column of silica gel with 7:3 cyclohexane-EtOAc
to give 17 (4.0 g, 99%) as a white solid: [R]D -3 (c 1.0, CHCl3);
1H NMR (CDCl3) δ 7.32-7.18 (m, 10H, Ph), 6.70 (d, 1H, J 2,NH
) 8.4 Hz, NHD), 5.82-5.78 (m, 1H, All), 5.20-5.05 (m, 2H,
All), 5.00 (m, 2H, H-3D, 4D), 4.75-4.45 (m, 4H, CH2Ph), 4.76
(d, 1H, J 1,2 ) 1.1 Hz, H-1A), 4.60 (d, 1H, J 1,2 ) 8.5 Hz, H-1D),
4.15-4.05 (m, 2H, J 5,6 ) 4.8 Hz, J 6a,6b ) 12.2 Hz, H-6aD, 6bD),
3.98 (m, 1H, H-2D), 3.90 (m, 2H, All), 3.86 (dd, 1H, J 2,3 ) 3.2
Hz, H-2A), 3.81 (dd, 1H, J 3,4 ) 9.5 Hz, H-3A), 3.62 (dq, 1H, J 4,5
) 9.5 Hz, J 5,6 ) 6.1 Hz, H-5A), 3.50 (m, 1H, H-5D), 3.32 (pt,
1H, H-4A), 2.02, 1.97, 1.93 (3 s, 9H, OAc), 1.24 (d, 3H, H-6A);
13C NMR (CDCl3) δ 171.0, 170.9, 169.6, 162.1 (CdO), 138.5-
117.1 (Ph, All), 101.8 (C-1D), 98.5 (C-1A), 92.6 (CCl3), 81.4 (C-
4A), 80.4 (C-3A), 77.1 (C-2A), 75.9, 74.1 (2C, CH2Ph), 72.7 (C-
3D), 72.5 (C-5D), 68.6 (C-4D), 68.3 (C-5A), 68.1 (All), 62.3 (C-
6D), 56.1 (C-2D), 21.1, 20.9, 20.9 (3C, OAc), 18.2 (C-6A). FAB-
MS for C37H44Cl3NO13 (M, 815), m/z 838 [M + Na]+. Anal.
Calcd for C37H44Cl3NO13: C, 54.39; H, 5.43; N, 1.71. Found:
C, 54.29; H, 5.45; N: 1.72.
The decasaccharide 1, corresponding to two consecutive
repeating units of the O-Ag of S. flexneri 2a, was synthe-
sized successfully based on the condensation of two key
pentasaccharide intermediates, the donor 46 and acceptor
48. Several routes to these two building blocks were
investigated, involving either blockwise strategies or a
linear one. The latter was the preferred one based on
yields of condensation and the number of steps.
Exp er im en ta l P r oced u r e
Gen er a l Meth od s. Optical rotations were measured for
CHCl3 solutions at 25 °C, expect where indicated otherwise.
TLC were performed on precoated slides of Silica Gel 60 F254
(Merck). Detection was effected when applicable, with UV
light, and/or by charring in 5% sulfuric acid in ethanol.
Preparative chromatography was performed by elution from
columns of Silica Gel 60 (particle size 0.040-0.063 mm). NMR
spectra were recorded at 25 °C for solutions in CDCl3 or D2O
(400 MHz for 1H, 100 MHz for 13C) except where otherwise
indicated. TMS (0.00 ppm for both 1H and 13C) was used as
an external reference for solutions in CDCl3. Proton-signal
assignments were made by first-order analysis of the spectra,
as well as analysis of 2D 1H-1H correlation maps (COSY) and
selective TOCSY experiments. Of the two magnetically non-
equivalent geminal protons at C-6, the one resonating at lower
field is denoted H-6a and the one at higher field is denoted
H-6b. The 13C NMR assignments were supported by 2D 13C-
1H correlation maps (HETCOR). Interchangeable assignments
are marked with an asterisk in the listing of signal assign-
ments. Sugar residues in oligosaccharides are serially lettered
according to the lettering of pentasaccharide I and identified
by a subscript in the listing of signal assignments. Fast atom
bombardment mass spectra (FAB-MS) were recorded in the
positive-ion mode with dithioerythridol/dithio-L-threitol (4:1,
MB) as the matrix, in the presence of NaI, and Xenon as the
gas. Anhydrous dichloromethane (DCM), 1,2-dichloroethane
(1,2-DCE), and Et2O, sold on molecular sieves, were used as
such. 4 Å powder molecular sieves was kept at 100 °C and
activated before use by heating at 250 °C under vacuum.
P h en yl (3,4,6-Tr i-O-a cet yl-2-d eoxy-2-t r ich lor oa cet a -
m id o-â-D-glu cop yr a n osyl)-(1f2)-3,4-d i-O-ben zyl-1-th io-r-
L-r h a m n op yr a n osid e (8). A mixture of alcohol 1538 (0.12 g,
0.27 mmol) and imidate 1634 (0.245 g, 0.41 mmol) in anhydrous
DCM (10 mL) was stirred for 15 min under dry Ar. After the
(3,4,6-Tr i-O-a cet yl-2-d eoxy-2-t r ich lor oa cet a m id o-â-D-
glu cop yr a n osyl)-(1f2)-3,4-d i-O-ben zyl-r-L-r h a m n op yr a -
n ose (18). 1,5-Cyclooctadiene-bis(methyldiphenylphosphine)-
iridium hexafluorophosphate (120 mg, 140 µmol) was dissolved
in THF (10 mL), and the resulting red solution was degassed
in an argon stream. Hydrogen was then bubbled through the
solution, causing the color to change to yellow. The solution
was then degassed again in an argon stream. A solution of 17
(1.46 g, 1.75 mmol) in THF (20 mL) was degassed and added.
The mixture was stirred at rt overnight, then concentrated.
The residue was taken up in acetone (27 mL) and water (3
mL). Mercuric bromide (949 mg, 2.63 mmol) and mercuric
oxide (761 mg, 3.5 mmol) were added, and the mixture,
protected from light, was stirred for 2 h at rt, then concen-
trated. The residue was taken up in DCM and washed three
times with satd aqueous KI, then with brine. The organic
phase was dried and concentrated. The residue was purified
by column chromatography (cyclohexane-EtOAc, 4:1) to give
1
18 (1.13 g, 81%) as a white foam: [R]D +4 (c 1.0, CHCl3); H
NMR (CDCl3) δ 7.35-7.05 (m, 10H, Ph), 6.74 (d, 1H, J 2,NH
)
8.5 Hz, NHD), 5.10 (d, 1H, J 1,2 ) 1.1 Hz, H-1A), 5.02 (m, 2H,
H-3D, 4D), 4.80-4.50 (m, 4H, CH2Ph), 4.61 (d, 1H, J 1,2 ) 8.5
Hz, H-1D), 4.15-4.08 (m, 2H, J 5,6 ) 4.5 Hz, J 6a,6b ) 12.3 Hz,
(47) Szurmai, Z.; Lipta´k, A.; Snatzke, G. Carbohydr. Res. 1990, 200,
201-208.
J . Org. Chem, Vol. 69, No. 4, 2004 1067

Be´lot et al.
H-6aD, 6bD), 4.00 (m, 1H, H-2D), 3.90 (dd, 1H, J 2,3 ) 3.3 Hz,
H-2A), 3.86 (dd, 1H, J 3,4 ) 9.5 Hz, H-3A), 3.85 (dq, 1H, J 4,5
hexafluorophosphate (10 mg, 12 µmol) was dissolved in THF
(10 mL), and the resulting red solution was processed as
described for the preparation of 18. A solution of 19 (830 mg,
1.16 mmol) in THF (40 mL) was degassed and added. The
mixture was stirred at rt overnight, then concentrated. The
residue was taken up in acetone (90 mL), and water (10 mL)
was added. Mercuric chloride (475 mg, 1.75 mmol) and
mercuric oxide (504 mg, 2.32 mmol) were added. The mixture,
protected from light, was stirred for 2 h at rt, then concen-
trated. The residue was taken up in DCM and washed three
times with satd aqueous KI, then with brine. The organic
phase was dried and concentrated. The residue was purified
by column chromatography (cyclohexane-EtOAc, 3:7) to give
20 (541 mg, 69%) as a white foam: [R]D +16 (c 1.0, CHCl3);
1H NMR (CDCl3) δ 7.35-7.05 (m, 10H, Ph), 5.50 (d, 1H, J 2,NH
) 8.2 Hz, NHD), 5.22 (d, 1H, J 1,2 ) 1.1 Hz, H-1A), 5.06 (pt, 1H,
J 3,4 ) J 4,5 ) 9.5 Hz, H-4D), 5.00 (pt, 1H, J 2,3 ) 9.5 Hz, H-3D),
4.85-4.60 (m, 4H, CH2Ph), 4.56 (d, 1H, J 1,2 ) 7.0 Hz, H-1D),
4.22-4.13 (m, 2H, J 5,6 ) 4.5 Hz, J 6a,6b ) 12.3 Hz, H-6aD, 6bD),
4.03 (m, 1H, H-2D), 4.00 (dq, 1H, J 4,5 ) 9.5 Hz, J 5,6 ) 6.2 Hz,
)
9.5 Hz, J 5,6 ) 6.2 Hz, H-5A), 3.50 (m, 1H, H-5D), 3.30 (pt, 1H,
H-4A), 2.85 (d, 1H, J 1,OH ) 3.5 Hz, OH), 2.02, 1.97, 1.94 (3s,
9H, OAc), 1.23 (d, 3H, H-6A); 13C NMR (CDCl3) δ 171.1, 170.0,
169.6, 162.1 (CdO), 138.5-127.1 (Ph), 101.7 (C-1D), 94.1 (C-
1A), 92.6 (CCl3), 81.4 (C-4A), 79.9 (C-2A), 77.3 (C-3A), 75.9, 74.1
(2C, CH2Ph), 72.7 (C-3D), 72.5 (C-5D), 68.6 (C-4D), 68.4 (C-5A),
62.2 (C-6D), 56.1 (C-2D), 21.1, 21.0, 20.9 (3C, OAc), 18.3 (C-
6A). FAB-MS for C34H40Cl3NO13 (M, 775), m/z 789 [M + Na]+.
Anal. Calcd for C34H40Cl3NO13
: C, 52.55; H, 5.19; N, 1.80.
Found: C, 52.48; H, 5.37; N, 1.67.
(3,4,6-Tr i-O-a cet yl-2-d eoxy-2-t r ich lor oa cet a m id o-â-D-
glu cop yr a n osyl)-(1f2)-3,4-d i-O-ben zyl-r-L-r h a m n op yr a -
n osyl Tr ich lor oa cetim id a te (6). The hemiacetal 18 (539 mg,
0.68 mmol) was dissolved in DCM (50 mL), placed under argon,
and cooled to 0 °C. Trichloroacetonitrile (0.6 mL, 6.8 mmol)
then DBU (10 µL, 70 µmol) were added. The mixture was
stirred at 0 °C for 30 min. The mixture was concentrated and
toluene was coevaporated from the residue. The residue was
eluted from a column of silica gel with 7:3 cyclohexane-EtOAc
containing 0.2% of Et3N to give 6 (498 mg, 78%) as a colorless
foam: [R]D -18 (c 1.0, CHCl3); 1H NMR (CDCl3) δ 8.48 (s, 1H,
NH), 7.40-7.15 (m, 10H, Ph), 6.75 (d, 1H, J 2,NH ) 8.5 Hz,
NHD), 6.18 (d, 1H, J 1,2 ) 1.1 Hz, H-1A), 5.15 (pt, 1H, J 2,3 ) J 3,4
) 9.5 Hz, H-3D), 5.07 (pt, 1H, J 4,5 ) 9.5 Hz, H-4D), 4.82-4.50
(m, 4H, CH2Ph), 4.62 (d, 1H, J 1,2 ) 8.5 Hz, H-1D), 4.20-4.03
(m, 2H, J 5,6 ) 4.5 Hz, J 6a,6b ) 12.3 Hz, H-6aD, 6bD), 3.98 (m,
1H, H-2D), 3.85 (dq, 1H, J 4,5 ) 9.5 Hz, J 5,6 ) 6.2 Hz, H-5A),
3.84 (dd, 1H, J 2,3 ) 3.3 Hz, H-2A), 3.83 (dd, 1H, J 3,4 ) 9.5 Hz,
H-3A), 3.55 (m, 1H, H-5D), 3.45 (pt, 1H, H-4A), 1.98, 1.96, 1.93
(3s, 9H, OAc), 1.23 (d, 3H, H-6A); 13C NMR (CDCl3) δ 171.1,
170.0, 169.6, 162.1 (CdO), 138.4-127.2 (Ph), 101.7 (C-1D), 97.2
(C-1A), 92.6 (CCl3), 80.5 (C-4A), 79.1 (C-3A), 76.2 (C-2A), 76.2,
74.1 (2C, CH2Ph), 74.4 (C-3D), 74.1 (C-5D), 71.3 (C-5A), 68.6
(C-4D), 62.3 (C-6D), 56.3 (C-2D), 21.1, 21.0, 20.9 (3C, OAc), 18.2
(C-6A). Anal. Calcd for C36H40Cl6N2O13: C, 46.93; H, 4.38; N,
3.04. Found: C, 46.93; H, 4.52; N, 2.85.
H-5A), 3.96 (dd, 1H, J 2,3 ) 3.3 Hz, H-2A), 3.90 (dd, 1H, J 3,4
)
9.5 Hz, H-3A), 3.60 (m, 1H, H-5D), 3.48 (d, 1H, J 1,OH ) 3.5 Hz,
OH), 3.40 (pt, 1H, H-4A), 2.08, 2.03, 2.01 (3s, 9H, OAc), 1.65
(s, 3H, NHAc), 1.30 (d, 3H, H-6A); 13C NMR (CDCl3) δ 171.2,
171.0, 170.4, 169.6 (CdO), 138.2-128.0 (Ph), 103.3 (C-1D), 94.1
(C-1A), 81.4 (C-4A), 79.9 (C-2A), 78.7 (C-3A), 75.8, 73.9 (2C, CH2-
Ph), 73.6 (C-3D), 72.4 (C-5D), 68.7 (C-4D), 68.2 (C-5A), 62.4 (C-
6D), 54.5 (C-2D), 23.3 (NHAc), 21.1, 21.0, 21.0 (3C, OAc), 18.3
(C-6A). FAB-MS for C34H43NO13 (M, 673.2), m/z 696.3 [M +
Na]+. Anal. Calcd for C34H43NO13: C, 60.61; H, 6.43; N, 2.08.
Found: C, 60.46; H, 6.61; N, 1.95.
(2-Aceta m id o-3,4,6-tr i-O-a cetyl-2-d eoxy-â-D-glu cop yr a -
n osyl)-(1f2)-3,4-d i-O-ben zyl-rr-L-r h a m n op yr a n osyl Tr i-
ch lor oa cetim id a te (7). The hemiacetal 20 (541 mg, 0.80
mmol) was dissolved in DCM (20 mL), placed under argon,
and cooled to 0 °C. Trichloroacetonitrile (0.81 mL, 8 mmol),
then DBU (10 µL, 80 µmol) were added. The mixture was
stirred at 0 °C for 1 h. The mixture was concentrated and
toluene was coevaporated from the residue. The residue was
eluted from a column of silica gel with 1:1 cyclohexane-EtOAc
containing 0.2% of Et3N to give 7 (560 mg, 86%) as a colorless
Allyl (2-Aceta m id o-3,4,6-tr i-O-a cetyl-2-d eoxy-â-D-glu -
cop yr a n osyl)-(1f2)-3,4-d i-O-ben zyl-r-L-r h a m n op yr a n o-
sid e (19). A mixture of the protected disaccharide 17 (3.0 g,
3.61 mmol) in MeOH (50 mL) was cooled to 0 °C and treated
with NH3 gas overnight. The solution was concentrated and
the residue (2.02 g) was dissolved again in MeOH (50 mL) and
treated with Ac2O (3.98 mL, 36.1 mol). The solution was stirred
for 2 h and then concentrated. The residue was eluted from a
column of silica gel with 95:5 DCM-EtOAC to give the
intermediate triol that was dissolved in pyridine (5 mL), cooled
to 0 °C, and treated with Ac2O (2.4 mL). The mixture was
stirred overnight and concentrated. The residue was eluted
from a column of silica gel with 3:2 cyclohexane-EtOAC to
give 19 (2.3 g, 90%) as a colorless foam: [R]D -12 (c 1.0,
CHCl3); 1H NMR (CDCl3) δ 7.32-7.18 (m, 10H, Ph), 5.80-
5.70 (m, 1H, All), 5.40 (d, 1H, J 2,NH ) 8.1 Hz, NH), 5.20-5.10
(m, 2H, All), 4.96 (pt, 1H, J 3,4 ) J 4,5 ) 9.5 Hz, H-4D), 4.90 (pt,
1H, J 2,3 ) 9.5 Hz, H-3D), 4.80 (d, 1H, J 1,2 ) 1.2 Hz, H-1A), 4.76-
4.52 (m, 4H, CH2Ph), 4.46 (d, 1H, J 1,2 ) 8.5 Hz, H-1D), 4.10-
4.02 (m, 2H, J 5,6 ) 4.7 Hz, J 6a,6b ) 11.2 Hz, H-6aD, 6bD), 3.92
(m, 1H, H-2D), 3.87 (m, 2H, All), 3.86 (dd, 1H, J 2,3 ) 3.5 Hz,
1
foam: [R]D +2 (c 1.0, CHCl3); H NMR (CDCl3) δ 8.56 (s, 1H,
NH), 7.50-7.20 (m, 10H, Ph), 6.29 (d, 1H, J 1,2 ) 1.3 Hz, H-1A),
5.50 (d, 1H, J 2,NH ) 8.3 Hz, NHD), 5.17 (pt, 1H, J 2,3 ) J 3,4
)
9.5 Hz, H-3D), 5.09 (dd, 1H, J 4,5 ) 9.5 Hz, H-4D), 4.85-4.60
(m, 4H, CH2Ph), 4.68 (d, 1H, J 1,2 ) 8.0 Hz, H-1D), 4.22-4.10
(m, 2H, J 5,6 ) 5.0 Hz, J 6a,6b ) 12.2 Hz, H-6aD, 6bD), 4.00 (m,
1H, H-2D), 3.99 (dd, 1H, J 2,3 ) 3.5 Hz, H-2A), 3.90 (dq, 1H, J 4,5
) 9.6 Hz, J 5,6 ) 6.2 Hz, H-5A), 3.89 (dd, 1H, J 3,4 ) 9.5 Hz,
H-3A), 3.62 (m, 1H, H-5D), 3.50 (dd, 1H, H-4A), 2.02, 2.00, 1.98
(3s, 9H, OAc), 1.65 (s, 3H, NHAc), 1.32 (d, 3H, H-6A); 13C NMR
(CDCl3) δ 171.2, 171.0, 170.4, 169.6 (CdO), 160.5 (CdNH),
138.2-128.0 (Ph), 103.3 (C-1D), 97.3 (C-1A), 91.4 (CCl3), 80.3
(C-4A), 79.9 (C-3A), 77.5 (C-2A), 76.0, 73.8 (2C, CH2Ph), 73.1
(C-3D), 72.2 (C-5D), 71.1 (C-5A), 68.8 (C-4D), 62.5 (C-6D), 54.8
(C-2D), 23.3 (NHAc), 21.4, 21.1, 21.0 (3C, OAc), 18.4 (C-6A).
Anal. Calcd for C36H43Cl3N2O13: C, 52.85; H, 5.30; N, 3.42.
Found: C, 52.85; H, 5.22; N, 3.47.
Allyl (2-O-Acetyl-3,4-d i-O-ben zyl-r-L-r h a m n op yr a n o-
syl)-(1f2)-3,4-di-O-ben zyl-r-L-r h am n opyr an oside (22). The
acceptor 14 (1.78 g, 4.65 mmol) and the trichloroacetimidate
donor 2142 (2.96 g, 5.58 mmol) were dissolved in anhydrous
Et2O (100 mL). The mixture was placed under argon and
cooled to -55 °C. TMSOTf (335 µL, 1.86 mmol) was added
dropwise. The mixture was stirred at -55 to -20 °C over 3 h.
Triethylamine (0.75 mL) was added, and the mixture was
allowed to warm to rt. The mixture was concentrated. The
residue was purified by column chromatography (cyclohexane-
EtOAc, 7:3) to give 22 as a colorless syrup (3.21 g, 92%): [R]D
-16 (c, 0.55, CHCl3) {lit.41 [R]D -19.3° (c, 1.2, CHCl3)}; 1H NMR
(CDCl3) δ 7.42-7.30 (m, 20H, Ph), 5.92-5.82 (m, 1H, All), 5.62
(dd, 1H, J 1,2 ) 1.6 Hz, J 2,3 ) 3.2 Hz, H-2A), 5.32-5.20 (m, 2H,
H-2A), 3.82 (dd, 1H, J 3,4 ) 9.5 Hz, H-3A), 3.62 (dq, 1H, J 4,5
)
9.5 Hz, J 5,6 ) 6.2 Hz, H-5A), 3.52 (m, 1H, H-5D), 3.30 (pt, 1H,
H-4A), 1.98, 1.94, 1.92 (3 s, 9H, OAc), 1.26 (d, 3H, H-6A); 13C
NMR (CDCl3) δ 171.1, 171.0, 170.3, 169.6 (CdO), 138-117 (Ph,
All), 103.4 (C-1D), 98.5 (C-1A), 81.3 (C-4A), 80.4 (C-3A), 78.5 (C-
2A), 75.9, 73.9 (2C, CH2Ph), 73.6 (C-3D), 72.4 (C-5D), 68.7 (C-
4D), 68.2 (C-5A), 68.1 (All), 62.5 (C-6D), 54.5 (C-2D), 23.4 (NHAc),
21.2, 21.1, 21.0 (3C, OAc), 18.1 (C-6A). FAB-MS for C37H47NO13
(M, 713.3), m/z 736.2 [M + Na]+. Anal. Calcd for C37H47NO13
:
C, 62.26; H, 6.64; N, 1.96. Found: C, 62.12; H, 6.79; N, 1.87.
(2-Aceta m id o-3,4,6-tr i-O-a cetyl-2-d eoxy-â-D-glu cop yr a -
n osyl)-(1f2)-3,4-d i-O-ben zyl-r/â-L-r h a m n op yr a n ose (20).
1,5-Cyclooctadiene-bis(methyldiphenylphosphine)iridium-
1068 J . Org. Chem., Vol. 69, No. 4, 2004

Convergent Synthesis of a Branched Decasaccharide
All), 5.07 (d, 1H, H-1A), 4.82 (d, 1H, J 1,2 ) 1.0 Hz, H-1B), 4.95-
4.60 (m, 8H, CH2Ph), 4.20-4.15 (m, 1H, All), 4.09 (d, 1H, J 2,3
) 3.0 Hz, H-2B), 4.05 (dd, 1H, J 3,4 ) 9.4 Hz, H-3A), 4.05-3.95
(m, 1H, All), 3.96 (dd, 1H, J 3,4 ) 9.5 Hz, H-3B), 3.89 (dq, 1H,
J 4,5 ) 9.5 Hz, J 5,6 ) 6.3 Hz, H-5A), 3.76 (dq, 1H, J 4,5 ) 9.5 Hz,
J 5,6 ) 6.2 Hz, H-5B), 3.52 (m, 1H, H-4B), 3.50 (m, 1H, H-4A),
2.18 (s, 3H, OAc), 1.39 (d, 3H, H-6A), 1.36 (d, 3H, H-6B); 13C
NMR (CDCl3) δ 170.8 (CdO), 138.4-117.1 (Ph, All), 99.5 (C-
1A), 98.4 (C-1B), 80.5 (2C, C-4A, 4B), 80.0 (C-3B), 78.1 (C-3A),
75.8, 75.7 (2C, CH2Ph), 74.9 (C-2B), 72.5, 72.2 (2C, CH2Ph),
69.3 (C-2A), 68.6 (C-5A), 68.4 (C-5B), 68.0 (All), 21.5 (OAc), 18.4,
18.2 (2C, C-6A, 6B). CI-MS for C45H52O10 (M, 752) m/z 770 [M
+ NH4]+. Anal. Calcd for C45H52O10: C, 71.79; H, 6.96. Found:
C, 70.95; H, 7.01.
Allyl (3,4-Di-O-b en zyl-r-L-r h a m n op yr a n osyl)-(1f2)-
3,4-d i-O-ben zyl-r-L-r h a m n op yr a n osid e (23). A 1 M solu-
tion of sodium methoxide in methanol (1.1 mL) was added to
a solution of 22 (3.10 g, 4.13 mmol) in methanol. The mixture
was stirred at rt for 3 h. The mixture was neutralized with
Amberlite IR-120 (H+) resin, filtered, and concentrated to give
23 (2.72 g, 93%) as a colorless syrup that crystallized on
standing: mp 98-99 °C (lit.21 mp 100 °C (hexane)); [R]D -30
(c 0.5, CHCl3) {lit.21 [R]D -32.5 (c, 0.4, CHCl3)}; 1H NMR
(CDCl3) δ 7.42-7.30 (m, 20H, Ph), 5.90-5.80 (m, 1H, All),
5.32-5.20 (m, 2H, All), 5.13 (d, 1H, J 1,2 ) 1.4 Hz, H-1A), 4.82
(d, 1H, J 1,2 ) 1.6 Hz, H-1B), 4.95-4.60 (m, 8H, CH2Ph), 4.20-
4.12 (m, 1H, All), 4.19 (m, 1H, J 2,3 ) 3.2 Hz, J 2,OH ) 1.8 Hz,
H-2A), 4.09 (d, 1H, J 2,3 ) 3.2 Hz, H-2B), 4.00-3.95 (m, 1H, All),
3.95 (dd, 1H, J 3,4 ) 9.4 Hz, H-3A), 3.93 (dd, 1H, J 3,4 ) 9.4 Hz,
H-3B), 3.87 (dq, 1H, J 4,5 ) 9.4 Hz, J 5,6 ) 6.2 Hz, H-5A), 3.74
(dq, 1H, J 4,5 ) 9.4 Hz, J 5,6 ) 6.2 Hz, H-5B), 3.53 (pt, 1H, H-4A),
3.46 (pt, 1H, H-4B), 2.52 (d, 1H, OH), 1.35 (m, 6H, H-6A, 6B);
13C NMR (CDCl3) δ 138.4-117.1 (Ph, All), 101.2 (C-1A), 98.4
(C-1B), 80.8, 80.4 (2C, C-4A, 4B), 80.3 (C-3B), 80.0 (C-3A), 75.8,
75.7 (2C, CH2Ph), 75.0 (C-2B), 72.7, 72.6 (2C, CH2Ph), 69.1 (C-
2A), 68.4 (C-5B), 68.3 (C-5A), 68.1 (All), 18.4, 18.3 (2C, C-6A,
6B). CI-MS for C43H50O9 (M, 710) m/z 728 [M + NH4]+.
CH2Ph), 72.2 (C-3D), 71.9 (C-5D), 71.6 (CH2Ph), 68.2 (C-5B*),
67.8 (C-4D), 67.5 (C-5A*), 67.5 (CH2O), 61.3 (C-6D), 55.7 (C-
2D), 20.5, 20.4 (3C, OAc), 17.9, 17.7 (2C, C-6A, 6B). FAB-MS
for C57H66Cl3NO17 (M, 1141.3) m/z 1164.3 [M + Na]+. Anal.
Calcd for C57H66Cl3NO17: C, 59.87; H, 5.82; N, 1.22. Found:
C, 59.87; H, 5.92; N, 1.16.
Allyl (3,4,6-Tr i-O-a cetyl-2-d eoxy-2-tetr a ch lor op h th a l-
im id o-â-D-glu cop yr a n osyl)-(1f2)-(3,4-d i-O-b en zyl-r-L-
r h am n opyr an osyl)-(1f2)-3,4-di-O-ben zyl-r-L-r h am n opyr a-
n osid e (28). Anhydrous Et2O (30 mL) and DCM (15 mL) were
added to the trichloroacetimidate donor 24 (3.34 g, 4.66 mmol)
and the acceptor 23 (2.20 g, 3.10 mmol). The mixture was
cooled to 0 °C and TMSOTf (85 µL, 0.466 mmol) was added
dropwise. The mixture was stirred at 0 °C for 1 h, then at rt
for 3 h. Triethylamine (1 mL) was added and the mixture was
stirred for 10 min, then concentrated. The mixture was taken
up in Et2O and the resulting precipitate was filtered off. The
filtrate was concentrated. The residue was purified by column
chromatography with 7:3 cyclohexane-EtOAc to give 28 (2.57
g, 65%) as a colorless amorphous solid: [R]D +22 (c 1.0, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.42-7.16 (m, 20H, Ph), 5.91
(dd, 1H, H-3D), 5.81 (m, 1H, All), 5.24-5.10 (m, 4H, H-1D, 4D,
All), 4.93 (s, 1H, H-1A), 4.81-4.53 (m, 5H, H-1B, CH2Ph), 4.45-
4.23 (m, 5H, H-2D, CH2Ph), 4.05 (m, 2H, H-6aD, All), 3.91-
3.58 (m, 8H, H-2A, 2B, 3A, 3B, 5A, 5B, 6bD, All), 3.38 (m, 1H,
H-5D), 3.21-3.13 (m, 2H, H-4A, 4B), 2.05, 2.02, 2.00 (3s, 9H,
OAc), 1.24 (m, 6H, H-6A, 6B); 13C NMR (75 MHz, CDCl3) δ
170.5, 170.4, 169.3 (CdO), 138.4-117.1 (Ph, All), 101.1 (C-
1A), 99.9 (C-1D), 97.7 (C-1B), 80.6 (2C, C-4A, 4B), 79.7, 78.9 (2C,
C-3A, 3B), 78.2 (C-2A), 76.3 (C-2B), 75.2, 75.1, 72.6, 71.3 (4C,
CH2Ph), 71.2 (C-5D), 70.1 (C-3D), 68.4 (C-5B*), 68.4 (C-4D), 67.6
(C-5A*), 67.6 (All), 61.3 (C-6D), 55.4 (C-2D), 20.6, 20.5 (3C, OAc),
18.0, 17.6 (2C, C-6A, 6B). FAB-MS for C63H65Cl4NO18 (M,
1263.3) m/z 1288.4, 1286.4 [M + Na]+. Anal. Calcd for C63H65
-
Cl4NO18: C, 59.77; H, 5.17; N, 1.11. Found: C, 60.19; H, 5.53;
N, 1.18.
Allyl (2-Aceta m id o-2-d eoxy-â-D-glu cop yr a n osyl)-(1f2)-
(3,4-d i-O-b en zyl-r-L-r h a m n op yr a n osyl)-(1f2)-3,4-d i-O-
ben zyl-r-L-r h a m n op yr a n osid e (26). The trisaccharide 25
(1.71 g, 1.50 mmol) was dissolved in MeOH (20 mL). A 1 M
solution of sodium methoxide in methanol (9 mL) and triethyl-
amine (5 mL) were added, and the mixture was stirred at rt
for 18 h. The mixture was cooled to 0 °C and acetic anhydride
was added dropwise until the pH reached 6. A further portion
of acetic anhydride (0.4 mL) was added, and the mixture was
stirred at rt for 30 min. The mixture was concentrated, and
toluene was coevaporated from the residue. The residue was
purified by column chromatography with 95:5 DCM-MeOH
to give 26 (623 mg, 45%) as a colorless amorphous solid: [R]D
3,4,6-Tr i-O-a cet yl-2-d eoxy-2-t et r a ch lor op h t h a lim id o-
â-D-glu cop yr a n osyl Tr ich lor oa cetim id a te (24).44 Trichlo-
roacetonitrile (2.5 mL) and anhydrous potassium carbonate
were added to a suspension of 3,4,6-tri-O-acetyl-2-deoxy-2-
tetrachlorophthalimido-R/â-D-glucopyranose (7.88 g, 13.75 mmol)
in 1,2-DCE (120 mL). The mixture was stirred at rt overnight.
TLC (cyclohexane-EtOAc, 3:2) showed that no starting mat-
erial remained. The mixture was filtered through a pad of
Celite, and the filtrate was concentrated to give the target 24
as a slightly brownish solid (9.08 g, 92%).
Allyl (3,4,6-Tr i-O-a cetyl-2-d eoxy-2-tr ich lor oa ceta m id o-
â-D-glu cop yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n o-
p yr a n osyl)-(1f2)-3,4-d i-O-b e n zyl-r-L-r h a m n op yr a n o-
sid e (25).1,2-DCE (35 mL)was added tothe trichloroacetimidate
donor 16 (2.49 g, 4.20 mmol), the acceptor 23 (2.48 g, 3.50
mmol), and 4 Å powdered molecular sieves (4 g). The mixture
was stirred for 1.5 h at rt under argon. The mixture was cooled
to -20 °C and TMSOTf (230 µL, 1.26 mmol) was added. The
temperature was allowed to rise to 0 °C over 1 h, and the
mixture was stirred for an additional 2 h at this temperature.
Triethylamine (0.5 mL) was added and the mixture was
allowed to warm to rt. The mixture was diluted with DCM
and filtered. The filtrate was concentrated. The residue was
purified by column chromatography with 3:1 cyclohexane-
EtOAc to give 25 (3.83 g, 96%) as a colorless amorphous solid:
[R]D -6 (c 0.5, CHCl3); 1H NMR (CDCl3) δ 7.52-7.28 (m, 20H,
Ph), 6.83 (d, 1H, J 2,NH ) 8.4 Hz, NH), 5.85 (m, 1H, All), 5.26-
5.09 (m, 4H, H-3D, 4D, All), 4.98 (d, 1H, J 1,2 ) 1.4 Hz, H-1A),
4.98-4.58 (m, 10H, H-1B, 1D, CH2Ph), 4.08 (m, 4H, H-2A, 2D,
6aD, All), 3.91 (m, 5H, H-2B, 3A, 3B, 6bD, All), 3.79 (m, 2H, H-5A,
5B), 3.45 (m, 3H, H-4A, 4B, 5D), 2.04, 2.02, 1.97 (3s, 9H, OAc),
1.30 (m, 6H, H-6A, 6B); 13C NMR (CDCl3) δ 170.6, 170.3, 169.1,
161.6 (CdO), 138.4-117.1 (Ph, All), 101.3 (C-1D), 100.9 (C-
1A), 97.6 (C-1B), 92.0 (CCl3), 80.9, 80.4 (2C, C-4A, 4B), 79.1, 79.0
(2C, C-3A, 3B), 77.3 (C-2A), 76.5 (C-2B), 75.4, 75.2, 73.6 (3C,
1
-16 (c 0.5, CHCl3); H NMR (300 MHz, CDCl3) δ 7.48-7.24
(m, 20H, Ph), 6.79 (d, 1H, NH), 5.73 (m, 1H, All), 5.12 (m, 3H,
H-1A, All), 4.86-4.52 (m, 9H, H-1B, CH2Ph), 4.34 (d, 1H, H-1D),
4.08-3.79 (m, 6H, H-2A, 2B, 3A, 3B, All), 3.74-3.53 (m, 3H,
H-5A, 5B, 6aD), 3.45-3.24 (m, 6H, H-2D, 3D, 4A, 4B, 4D, 6bD),
3.20 (m, 1H, H-5D), 1.46 (s, 3H, NHAc), 1.24 (m, 6H, H-6A, 6B);
13C NMR (75 MHz, CDCl3) δ 173.6 (CdO), 137.4-117.3 (Ph,
All), 103.2 (C-1D), 100.3 (C-1A), 97.9 (C-1B), 81.3, 80.4 (2C, C-4A,
4B), 79.9 (2C, C-3A, 3B), 79.9 (C-2B*), 78.9 (C-3D), 75.7 (C-5D),
75.6, 75.3, 74.5 (3C, CH2Ph), 73.6 (C-2A*), 72.5 (CH2Ph), 71.9
(C-4D), 68.2, 68.0 (2C, C-5A, 5B), 67.7 (CH2O), 62.5 (C-6D), 58.8
(C-2D), 22.3 (NHAc), 18.0, 17.8 (2C, C-6A, 6B). FAB-MS for
C
C
51H63NO14 (M, 913.4) m/z 936.6 [M + Na]+. Anal. Calcd for
51H63NO14‚H2O: C, 65.72; H, 7.03; N, 1.50. Found: C, 65.34;
H, 7.03; N, 1.55.
Allyl (2-Aceta m id o-3,4,6-tr i-O-a cetyl-2-d eoxy-â-D-glu -
cop yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n op yr a n o-
syl)-(1f2)-3,4-d i-O-ben zyl-r-L-r h a m n op yr a n osid e (27). (a)
Pyridine (5 mL) was added to 26 (502 mg, 0.55 mmol) and the
mixture was cooled to 0 °C. Acetic anhydride (3 mL) was added.
The mixture was stirred at rt for 18 h. The mixture was
concentrated and toluene was coevaporated from the residue.
The residue was taken up in DCM and washed successively
J . Org. Chem, Vol. 69, No. 4, 2004 1069

Be´lot et al.
with 5% aq HCl and saturated aq NaHCO3. The organic phase
was dried and concentrated to give 27 (538 mg, 94%) as a
colorless foam.
dissolved in DCM (10 mL), placed under argon, and cooled to
0 °C. Trichloroacetonitrile (0.6 mL, 6 mmol), then DBU (10
µL, 59 µmol) were added. The mixture was stirred at 0 °C for
20 min, then at rt for 20 min. The mixture was concentrated
and toluene was coevaporated from the residue. The residue
was purified by flash chromatography with 1:1 cyclohexane-
EtOAc containing 0.2% of Et3N to give 13 (634 mg, 94%) as a
colorless foam. The 1H NMR spectra showed the R:â ratio to
be 10:1: [R]D -20 (c 1, CHCl3); 1H NMR (300 MHz, CDCl3)
R-anomer, δ 8.47 (s, 1H, CdNH), 7.38-7.20 (m, 20H, Ph), 6.10
(d, 1H, J 1,2 ) 1.3 Hz, H-1B), 5.40 (d, 1H, NH), 5.01 (m, 1H,
H-4D), 4.95 (d, 1H, J 1,2 ) 1.2 Hz, H-1A), 4.89 (m, 1H, H-3D),
4.85-4.55 (m, 9H, H-1D, CH2Ph), 4.07 (dd, 1H, H-6aD), 4.03
(m, 1H, H-2A), 3.97 (m, 1H, H-2D), 3.91 (dd, 1H, H-6bD), 3.85-
3.71 (m, 5H, H-2B, 3A, 3B, 5A, 5B), 3.45-3.31 (m, 3H, H-4A, 4B,
5D), 1.99, 1.96, 1.91, 1.58 (4s, 12H, OAc, NHAc), 1.26 (m, 6H,
H-6A, 6B); 13C NMR (75 MHz, CDCl3) δ 171.1, 170.9, 170.3,
169.6 (CdO), 160.6 (CdNH), 138.6-128.1 (Ph), 103.3 (C-1D),
101.6 (C-1A), 96.9 (C-1B), 91.3 (CCl3), 81.4, 80.2 (2C, C-4A, 4B),
79.9, 78.5 (2C, C-3A, 3B), 78.3 (C-2A), 75.9 (2C, CH2Ph), 75.0
(C-2B), 73.7 (CH2Ph), 73.7 (C-3D), 72.4 (CH2Ph), 72.4 (C-5D),
71.0, 69.0 (2C, C-5A, 5B), 68.5 (C-4D), 62.1 (C-6D), 54.6 (C-2D),
23.4 (NHAc), 21.1, 21.0 (3C, OAc), 18.5, 18.0 (2C, C-6A, 6B).
Anal. Calcd for C56H65Cl3N2O17: C, 58.77; H, 5.72; N, 2.45.
Found: C, 58.78; H, 5.83; N, 2.45.
(b) THF (3 mL) and ethanol (3.3 mL) were added to 28 (384
mg, 0.30 mmol). Ethylenediamine (90 µL, 1.36 mmol) was
added and the mixture was heated at 55 °C for 4 h. The
mixture was allowed to cool to rt. Acetic anhydride (1.0 mL)
was added, and the mixture was stirred at rt for 1.5 h. The
mixture was concentrated. The residue was taken up in
pyridine (5 mL) and the mixture was cooled to 0 °C. Acetic
anhydride (2.5 mL) was added. The mixture was stirred at rt
for 18 h. The mixture was concentrated and toluene was
coevaporated from the residue. The residue was taken up in
DCM, which caused the formation of a white precipitate. The
mixture was filtered through a plug of silica gel, eluting with
7:3 cyclohexane-acetone. The filtrate was concentrated to give
27 (215 mg, 68%) as a colorless foam: [R]D -7 (c 0.5, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.48-7.24 (m, 20H, Ph), 5.84
(m, 1H, All), 5.53 (d, 1H, NH), 5.19 (m, 2H, All), 5.03 (dd, 1H,
H-4D), 4.98 (m, 2H, H-1A, 3D), 4.95-4.54 (m, 10H, H-1B, 1D,
CH2Ph), 4.07 (m, 4H, H-2A, 2D, 6aD, All), 3.88 (m, 5H, H-2B,
3A, 3B, 6bD, All), 3.79, 3.68 (2m, 2H, H-5A, 5B), 3.42 (m, 3H,
H-4A, 4B, 5D), 2.02, 2.01, 1.97, 1.64 (4s, 12H, OAc, NHAc), 1.30
(m, 6H, H-6A, 6B); 13C NMR (75 MHz, CDCl3) δ 170.7, 170.4,
169.9, 169.1 (CdO), 138.5-117.1 (Ph, All), 102.9 (C-1D), 101.2
(C-1A), 97.7 (C-1B), 81.0, 80.5 (2C, C-4A, 4B), 79.5, 79.1 (2C,
C-3A, 3B), 78.2 (C-2A), 76.1 (C-2B), 75.5, 75.2, 73.6 (CH2Ph), 73.3
(C-3D), 71.9 (C-5D), 71.7 (CH2Ph), 68.3 (C-5A*), 68.0 (C-4D), 67.6
(C-5B*), 67.6 (CH2O), 61.6 (C-6D), 54.1 (C-2D), 22.9 (NHAc),
20.7, 20.6 (3C, OAc), 18.0, 17.7 (2C, C-6A, 6B). FAB-MS for
Allyl (2-Aceta m id o-3,4,6-tr i-O-a cetyl-2-d eoxy-â-D-glu -
cop yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n op yr a n o-
syl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n op yr a n osyl)-(1f3)-
[2,3,4,6-t et r a -O-b en zyl-r-D-glu cop yr a n osyl-(1f4)]-2-O-
ben zoyl-r-L-r h a m n op yr a n osid e (5). Anhydrous Et2O (5 mL)
was added to the donor 13 (500 mg, 0.44 mmol), the acceptor
1118 (242 mg, 0.29 mmol), and powdered 4 Å molecular sieves.
The mixture was placed under argon and cooled to 0 °C. Boron
trifluoride etherate (415 µL, 3.27 mmol) was added. The
mixture was stirred at 0 °C for 1 h, then at rt for 18 h. The
mixture was diluted with DCM and triethylamine (1 mL) was
added. The mixture was filtered through a pad of Celite and
the filtrate was concentrated. The residue was purified by
column chromatography with 3:2 cyclohexane-EtOAc to give,
in order, the acceptor 11 (132 mg, 54%), 5 (231 mg, 44%), and
the hemiacetal 29 (129 mg, 29%). The desired pentasaccharide
5 was obtained as a colorless foam: [R]D +10 (c 1.0, CHCl3);
1H NMR (CDCl3) δ 8.02-7.09 (m, 45H, Ph), 5.92 (m, 1H, All),
5.65 (d, 1H, NH), 5.37 (m,1H, H-2C), 5.19 (m, 2H, All), 5.13
(br s, 1H, H-1A), 4.96-4.35 (m, 15H, H-1B, 1C, 1D, 1E, 2B, 3D,
4D, CH2Ph), 4.17 (m, 2H, H-2A, All), 4.04-3.87 (m, 8H, H-2D,
3A, 3C, 3E, 5A, 5E, 6aD, All), 3.81-3.63 (m, 7H, H-3B, 4C, 4E, 5C,
6aE, 6bE, 6bD), 3.59 (m, 1H, H-5B), 3.43 (m, 3H, H-2E, 4A, 5D),
3.28 (pt, 1H, H-4B), 2.01, 1.99, 1.71, 1.66 (4s, 12H, OAc, NHAc),
1.34 (m, 6H, H-6A, 6C), 1.00 (d, 3H, H-6B); 13C NMR (CDCl3) δ
170.5, 170.0, 169.3, 165.8, 163.5 (CdO), 138.7-117.6 (Ph, All),
102.7 (C-1D), 100.8 (2C, C-1A, 1B), 98.1 (C-1E), 95.9 (C-1C), 81.8
(C-3E), 81.2 (2C, C-2E, 4A), 80.0 (C-4B), 79.7 (2C, C-3A, 3C), 78.2
(C-3B), 77.7 (C-2A), 77.3 (2C, C-4C, 4E), 75.6, 75.4, 74.9 (CH2-
Ph), 74.3 (C-2B), 73.8 (CH2Ph), 73.7 (C-3D), 72.8 (CH2Ph), 72.3
(C-2C), 72.1 (C-5D), 71.5 (C-5E), 70.2 (CH2Ph), 68.5 (C-5B), 68.4
(C-5A, CH2O), 68.2 (C-4D), 67.9 (C-6E), 67.4 (C-5C), 61.8 (C-6D),
54.3 (C-2D), 23.1 (NHAc), 20.7, 20.6, 20.4 (3C, OAc), 18.6 (C-
6A), 18.0 (C-6C), 17.8 (C-6B). FAB-MS for C104H117NO27 (M,
C
57H69NO17 (M, 1039.5) m/z 1062.4 [M + Na]+. Anal. Calcd
for C57H69NO17: C, 65.82; H, 6.69; N, 1.35. Found: C, 65.29;
H, 6.82; N, 1.29.
(2-Aceta m id o-3,4,6-tr i-O-a cetyl-2-d eoxy-â-D-glu cop yr a -
n osyl)-(1f2)-(3,4-di-O-ben zyl-r-L-r h am n opyr an osyl)-(1f2)-
3,4-d i-O-ben zyl-r/â-L-r h a m n op yr a n ose (29). 1,5-Cyclooc-
tadiene-bis(methyldiphenylphosphine)iridium hexafluorophos-
phate (30 mg, 35 µmol) was dissolved in THF (5 mL), and the
resulting red solution was processed as described for the
preparation of 18. A solution of 27 (805 mg, 0.775 mmol) in
THF (10 mL) was degassed and added. The mixture was
stirred at rt overnight, then concentrated. The residue was
taken up in acetone (15 mL) and water (1.5 mL). Mercuric
chloride (315 mg, 1.16 mmol) and mercuric oxide (335 mg, 1.55
mmol) were added. The mixture, protected from light, was
stirred for 1 h at rt, then concentrated. The residue was taken
up in DCM and washed three times with satd aqueous KI,
then with brine. The organic phase was dried and concen-
trated. The residue was purified by column chromatography
with 2:3 EtOAc-cyclohexane to give 29 (645 mg, 83%) as a
white foam. The 1H NMR spectra showed the R:â ratio to be
3.3:1; [R]D +3 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3)
R-anomer, δ 7.47-7.30 (m, 20H, Ph), 5.53 (d, 1H, NH), 5.17
(d, 1H, J 1,2 ) 1.9 Hz, H-1B), 5.08 (m, 1H, H-4D), 5.03 (d, 1H,
J 1,2 ) 1.5 Hz, H-1A), 4.99 (m, 1H, H-3D), 4.92-4.62 (m, 8H,
CH2Ph), 4.60 (d, 1H, J 1,2 ) 8.4 Hz, H-1D), 4.18-4.01 (m, 3H,
H-2A, 2D, 6aD), 3.97-3.90 (m, 5H, H-2B, 3A, 3B, 5A*, 6bD), 3.83
(m, 1H, H-5B*), 3.45-3.37 (m, 3H, H-4A, 4B, 5D), 2.04, 2.03,
1.99, 1.68 (4s, 12H, OAc, NHAc), 1.32 (m, 6H, H-6A, 6B); 13C
NMR (75 MHz, CDCl3) R-anomer, δ 170.7, 170.4, 169.9, 169.1
(CdO), 138.5-129.3 (Ph), 103.3 (C-1D), 101.6 (C-1A), 93.9 (C-
1B), 81.5, 80.8 (2C, C-4A, 4B), 79.9, 78.9 (2C, C-3A, 3B), 78.6
(C-2A), 76.8 (C-2B), 76.0, 75.5, 74.0 (3C, CH2Ph), 73.7 (C-3D),
72.4 (C-5D), 72.2 (CH2Ph), 68.7 (C-5A*), 68.5 (C-4D), 68.2 (C-
5B*), 62.0 (C-6D), 54.6 (C-2D), 23.4 (NHAc), 21.1, 21.0 (3C, OAc),
18.5, 18.1 (2C, C-6A, 6B). FAB-MS for C54H65NO17 (M, 999.4)
m/z 1022.5 [M + Na]+. Anal. Calcd for C54H65NO17: C, 64.85;
H, 6.55; N, 1.40. Found: C, 64.55; H, 7.16; N, 1.15.
1812.1) m/z 1836.2, 1835.2 [M + Na]+. Anal. Calcd for C104H117
-
NO27: C, 68.90; H, 6.50; N, 0.77. Found: C, 68.64; H, 6.66; N,
1.05.
Allyl (3,4-Di-O-ben zyl-2-O-ch lor oacetyl-r-L-r h am n opyr -
an osyl)-(1f2)-3,4-di-O-ben zyl-r-L-r h am n opyr an oside (32).
To a solution of 23 (3.8 g, 5.35 mmol) in pyridine (40 mL) was
added chloroactic anhydride (1.83 g, 10.7 mmol) at 0 °C. The
mixture was stirred overnight at 0 °C. MeOH (10 mL) was
added and the mixture was concentrated. The residue was
eluted from a column of silica gel with 95:5 cyclohexane-
acetone to give 32 (2.4 g, 57%) as a colorless syrup: [R]D -15
(c 1.0, CHCl3); 1H NMR (CDCl3) δ 7.30-7.15 (m, 20H, Ph),
5.81-5.71 (m, 1H, All), 5.49 (dd, 1H, J 1,2 ) 1.7 Hz, J 2,3 ) 3.2
(2-Aceta m id o-3,4,6-tr i-O-a cetyl-2-d eoxy-â-D-glu cop yr a -
n osyl)-(1f2)-(3,4-di-O-ben zyl-r-L-r h am n opyr an osyl)-(1f2)-
3,4-d i-O-ben zyl-r/â-L-r h a m n op yr a n osyl Tr ich lor oa cetim -
id a te (13). The hemiacetal 29 (595 mg, 0.59 mmol) was
1070 J . Org. Chem., Vol. 69, No. 4, 2004

Convergent Synthesis of a Branched Decasaccharide
Hz, H-2A), 5.20-5.08 (m, 2H, All), 4.90 (d, 1H, H-1A), 4.84-
4.50 (m, 8H, PhCH2), 4.65 (d, 1H, J 1,2 < 1.0 Hz, H-1B), 4.04-
3.85 (m, 2H, All), 4.02 (m, 2H, CH2Cl), 3.93 (dd, 1H, J 2,3 ) 3.0
Hz, H-2B), 3.88 (dd, 1H, J 3,4 ) 9.5 Hz, H-3A), 3.81 (pt, 1H, J 3,4
) 9.5 Hz, H-3B), 3.73 (dq, 1H, J 4,5 ) 9.5 Hz, J 5,6 ) 6.2 Hz,
H-5A), 3.62 (dq, 1H, J 4,5 ) 9.0 Hz, J 5,6 ) 6.1 Hz, H-5B), 3.34
(dd, 1H, H-4B), 3.30 (dd, 1H, H-4A), 1.22 (d, 3H, H-6A), 1.21 (d,
3H, H-6B); 13C NMR (CDCl3) δ 166.9 (CdO), 138.5-117.2 (Ph,
All), 99.2 (C-1A), 98.2 (C-1B), 80.4 (C-4A), 80.3 (C-3B), 80.2 (C-
4B), 77.9 (C-3A), 75.8, 75.7, 72.6, 72.4 (4C, PhCH2), 74.9 (C-
2B), 71.2 (C-2A), 68.6 (C-5A), 68.4 (C-5B), 68.0 (All), 41.3 (CH2Cl),
18.3 (2C, C-6A, 6B). FAB-MS for C45H51ClO10 (M, 786.3), m/z
809.3 [M + Na]+. Anal. Calcd for C45H51ClO10: C, 68.65; H,
6.53. Found: C, 68.51; H, 6.67.
mg, 8.02 mmol) was added in 3 parts, one part each 10 min.
Then pMeOBnCl (1.8 mL, 13.34 mmol) was added and the
mixture was stirred overnight at rt. MeOH (5 mL) was added
and the solution was stirred for 10 min. The solution was
concentrated and the residue was eluted from a column of
silica gel with 95:5 cyclohexane-acetone to give 35 (4.34 g,
97%) as a colorless syrup: [R]D
-8 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3) δ 7.20-6.80 (m, 24H, Ph), 5.90-5.80 (m,
1H, All), 5.30-5.15 (m, 2H, All), 5.12 (d, 1H, J 1,2 < 1.0 Hz,
H-1A), 4.73 (d, 1H, J 1,2 < 1.0 Hz, H-1B), 4.70-4.40 (m, 10H,
PhCH2), 4.20-4.08 (m, 1H, All), 4.10 (dd, 1H, J 2,3 ) 3.0 Hz,
H-2B), 3.95-3.88 (m, 3H, H-3A, 3B, All), 3.80-3.78 (m, 2H, J 4,5
) 9.4 Hz, J 5,6 ) 6.1 Hz, H-2A, 5A), 3.72 (s, 3H, OCH3), 3.70 (m,
1H, J 4,5 ) 9.4 Hz, J 5,6 ) 6.1 Hz, H-5B), 3.61 (dd, 1H, H-4A),
3.32 (dd, 1H, H-4B), 1.18 (d, 3H, H-6A), 1.10 (d, 3H, H-6B); 13
C
(3,4-Di-O-ben zyl-2-O-ch lor oa cetyl-r-L-r h a m n op yr a n o-
syl)-(1f2)-3,4-di-O-ben zyl-r/â-L-r h am n opyr an ose (33). 1,5-
Cyclooctadiene-bis(methyldiphenylphosphine)iridium hexaflu-
orophosphate (40 mg, 46 µmol) was dissolved in THF (7 mL),
and the resulting red solution was processed as described for
the preparation of 18. A solution of 32 (2.39 g, 3.04 mmol) in
THF (18 mL) was degassed and added. The mixture was
stirred at rt overnight. The mixture was concentrated. The
residue was taken up in acetone (30 mL) and water (5 mL).
Mercuric chloride (1.24 g, 4.56 mmol) and mercuric oxide (1.3
g, 6.08 mmol) were added. The mixture, protected from light,
was stirred for 2 h at rt, then concentrated. The residue was
taken up in DCM and washed three times with satd aqueous
KI, then with brine. The organic phase was dried and
concentrated. The residue was purified by column chromatog-
raphy (cyclohexane-EtOAc, 4:1) to give 33 (1.91 g, 84%) as a
white foam: [R]D -2 (c 1.0, CHCl3); 1H NMR (CDCl3) δ 7.40-
7.10 (m, 20H, Ph), 5.49 (dd, 1H, J 1,2 ) 1.7 Hz, J 2,3 ) 3.2 Hz,
H-2A), 4.99 (d, 1H, J 1,2 < 1.0 Hz, H-1B), 4.90 (d, 1H, H-1A),
4.85-4.45 (m, 8H, PhCH2), 4.01 (m, 2H, CH2Cl), 3.93 (dd, 1H,
J 2,3 ) 3.0 Hz, H-2B), 3.90 (dd, 1H, J 3,4 ) 9.3 Hz, H-3A), 3.84
(dd, 1H, J 3,4 ) 9.0 Hz, H-3B), 3.81 (dq, 1H, J 4,5 ) 9.0 Hz, J 5,6
) 6.2 Hz, H-5B), 3.72 (dq, 1H, J 4,5 ) 9.5 Hz, J 5,6 ) 6.2 Hz,
H-5A), 3.33 (pt, 1H, H-4B), 3.30 (dd, 1H, H-4A), 2.81 (d, 1H,
NMR (75 MHz, CDCl3) δ 133.9-113.8 (Ph, All), 99.0 (C-1A),
97.8 (C-1B), 80.4 (C-4A), 80.2 (C-4B), 80.0 (C-3B), 79.0 (C-3A),
75.2, 72.3, 71.8, 71.5, 71.3, 67.5 (5C, PhCH2, All), 74.1 (C-2A),
73.8 (C-2B), 68.3 (C-5A), 67.8 (C-5B), 55.0 (OCH3), 17.8, 17.9
(2C, C-6A, 6B). FAB-MS for C51H58O10 (M, 830.4) m/z 853.5 [M
+ Na]+. Anal. Calcd for C51H58O10: C, 73.71; H, 7.03. Found:
C, 73.57; H, 7.21.
(3,4-Di-O-ben zyl-2-O-p-m eth oxyben zyl-r-L-r h a m n op y-
r a n osyl)-(1f2)-3,4-d i-O-ben zyl-r-L-r h a m n op yr a n ose (36).
1,5-Cyclooctadiene-bis(methyldiphenylphosphine)iridium-
hexafluorophosphate (50 mg, 60 µmol) was dissolved in THF
(6 mL), and the resulting red solution was processed as
described for the preparation of 18. A solution of 35 (4.23 g,
5.09 mmol) in THF (24 mL) was degassed and added. The
mixture was stirred at rt overnight, then concentrated. The
residue was taken up in acetone (45 mL), and water (5 mL)
was added. Mercuric chloride (2.07 g, 7.63 mmol) and mercuric
oxide (2.2 g, 10.2 mmol) were added. The mixture, protected
from light, was stirred for 2 h at rt, then concentrated. The
residue was taken up in DCM and washed three times with
satd aqueous KI, then with brine. The organic phase was dried
and concentrated. The residue was purified by column chro-
matography (cyclohexane-EtOAc, 4:1) to give 36 (2.97 g, 73%)
J 2,OH ) 3.4 Hz, OH), 1.22 (d, 3H, H-6A), 1.20 (d, 3H, H-6B); 13
C
1
as a white foam: [R]D +8 (c 1.0, CHCl3); H NMR (300 MHz,
NMR (CDCl3) δ 167.0 (CdO), 138.5-127.2 (Ph), 99.1 (C-1A),
93.9 (C-1B), 80.3 (C-4B), 80.2 (C-4A), 79.7 (C-3B), 77.8 (C-3A),
75.8, 75.7, 72.6, 72.4 (4C, PhCH2), 75.0 (C-2B), 71.1 (C-2A), 68.6
(C-5A), 68.4 (C-5B), 41.3 (CH2Cl), 18.1 (2C, C-6A, 6B). FAB-MS
for C42H47ClO10 (M, 746.3), m/z 769.3 [M + Na]+. Anal. Calcd
for C42H47ClO10: C, 67.51; H, 6.34. Found: C, 67.46; H, 6.39.
CDCl3) δ 7.40-7.25 (m, 20H, Ph), 7.18-6.73 (m, 4H, Ph), 5.12
(d, 1H, J 1,2
< 1.0 Hz, H-1A), 5.05 (d, 1H, J 1,2 < 1.0 Hz, H-1B),
4.80-4.40 (m, 10H, PhCH2), 4.08 (dd, 1H, J 2,3 ) 3.0 Hz, H-2B),
3.90-3.80 (m, 2H, J 3,4 ) J 4,5 ) 9.5 Hz, J 5,6 ) 6.1 Hz, H-3B,
5B), 3.80-3.78 (m, 2H, J 2,3 ) 3.1 Hz, J 4,5 ) 9.4 Hz, J 5,6 ) 6.1
Hz, H-2A, 5A), 3.73 (m, 1H, J 3,4 ) 9.4 Hz, H-3A), 3.72 (s, 3H,
OCH3), 3.60 (pt, 1H, H-4A), 3.33 (pt, 1H, H-4B), 1.34 (d, 3H,
H-6A), 1.24 (d, 3H, H-6B); 13C NMR (75 MHz, CDCl3) δ 113.2-
129.8 (Ph), 99.1 (C-1A), 93.8 (C-1B), 80.7 (C-4A), 80.3 (C-4B),
79.7 (C-3B), 79.2 (C-3A), 75.5, 75.4, 72.6, 72.5, 72.4 (5C, PhCH2),
74.2 (C-2A), 74.1 (C-2B), 68.5 (C-5A), 68.1 (C-5B), 55.3 (OCH3),
18.1 (2C, C-6A, 6B). FAB-MS for C48H54O10 (M, 790.4) m/z 813.4
(3,4-Di-O-ben zyl-2-O-ch lor oa cetyl-r-L-r h a m n op yr a n o-
syl)-(1f2)-3,4-d i-O-ben zyl-r-L-r h a m n op yr a n osyl Tr ich lo-
r oa cetim id a te (34). The hemiacetal 33 (1.80 g, 2.41 mmol)
was dissolved in DCM (25 mL), placed under argon, and cooled
to 0 °C. Trichloroacetonitrile (2.4 mL, 24 mmol), then DBU
(35 µL, 0.24 mmol) were added. The mixture was stirred at 0
°C for 40 min. The mixture was concentrated and toluene was
coevaporated from the residue. The residue was eluted from
a column of silica gel with 4:1 cyclohexane-EtOAc containing
0.2% of Et3N to give 34 (1.78 g, 83%) as a colorless foam: [R]D
-12 (c 1.0, CHCl3); 1H NMR (CDCl3) δ 8.60 (s, 1H, NH), 7.50-
7.30 (m, 20H, Ph), 6.21 (d, 1H, J 1,2 ) 1.8 Hz, H-1B), 5.63 (dd,
1H, J 1,2 ) 1.5 Hz, J 2,3 ) 3.2 Hz, H-2A), 5.07 (d, 1H, H-1A), 5.00-
4.65 (m, 8H, PhCH2), 4.19 (m, 2H, CH2Cl), 4.09 (dd, 1H, J 2,3
) 3.2 Hz, H-2B), 4.04 (dd, 1H, J 3,4 ) 9.0 Hz, H-3B), 3.95 (m,
3H, H-3A, 5A, 5B), 3.58 (dd, 1H, H-4A), 3.48 (dd, 1H, H-4B), 1.39
(m, 6H, H-6A, 6B); 13C NMR (CDCl3) δ 167.1 (CdO), 160.7 (Cd
N), 138.3-127.0 (Ph), 99.4 (C-1A), 97.5 (C-1B), 91.4 (CCl3), 80.1
(C-4B), 80.0 (C-4A), 79.2 (C-3A), 77.9 (C-3B), 75.9, 75.8, 73.0,
72.6 (4C, PhCH2), 73.7 (C-2B), 71.4 (C-2A), 71.2, 68.9 (2C, C-5A,
5B), 41.3 (CH2Cl), 18.4, 18.2 (2C, C-6A, 6B). Anal. Calcd for
[M + Na]+. Anal. Calcd for C48H54O10
Found: C, 72.86; H, 6.98.
: C, 72.89; H, 6.88.
(3,4-Di-O-ben zyl-2-O-p-m eth oxyben zyl-r-L-r h a m n op y-
r a n osyl)-(1f2)-3,4-d i-O-b en zyl-r/â-L-r h a m n op yr a n osyl
Tr ich lor oa cetim id a te (37). The hemiacetal 36 (2.1 g, 2.66
mmol) was dissolved in DCM (20 mL), placed under argon,
and cooled to 0 °C. Trichloroacetonitrile (2.7 mL, 26 mmol),
then DBU (40 µL, 0.26 mmol) were added. The mixture was
stirred at 0 °C for 30 min. The mixture was concentrated and
toluene was coevaporated from the residue. The residue was
eluted from a column of silica gel with 8:2 cyclohexane-EtOAc
containing 0.2% of Et3N to give 37 (2.03 g, 82%) as a colorless
1
foam: [R]D -10 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3) δ
8.50 (s, 1H, NH), 7.25-7.05 (m, 20H, Ph), 7.05-6.62 (m, 4H,
Ph), 6.08 (d, 1H, J 1,2 < 1.0 Hz, H-1B), 5.10 (d, 1H, J 1,2 < 1.0
C
44H47Cl4NO10: C, 59.27; H, 5.31; N, 1.57. Found: C, 59.09;
Hz, H-1A), 4.80-4.40 (m, 10H, PhCH2), 4.10 (dd, 1H, J 2,3
)
H, 5.49; N, 1.53.
3.0 Hz, H-2B), 3.90-3.80 (m, 4H, H-3B, 2A, 3A, 5A), 3.80-3.72
(m, 1H, H-5B), 3.72 (s, 3H, OCH3), 3.63 (pt, 1H, J 3,4 ) J 4,5
Allyl (3,4-Di-O-ben zyl-2-O-p-m eth oxyben zyl-r-L-r h a m -
n op yr a n osyl)-(1f2)-3,4-d i-O-ben zyl-r-L-r h a m n op yr a n o-
sid e (35). The alcohol 23 (3.8 g, 5.35 mmol) was dissolved in
DMF (25 mL). The mixture was cooled to 0 °C and NaH (320
)
9.5 Hz, H-4A), 3.42 (pt, 1H, J 3,4 ) J 4,5 ) 9.5 Hz, H-4B), 1.30 (d,
3H, H-6B), 1.25 (d, 3H, H-6A); 13C NMR (75 MHz, CDCl3) δ
161.1 (CdNH), 129.5-113.4 (Ph), 99.6 (C-1A), 97.0 (C-1B), 80.6
J . Org. Chem, Vol. 69, No. 4, 2004 1071

Be´lot et al.
(C-4A), 79.6 (C-4B), 79.3 (2C, C-3A, 3B), 75.7, 75.5, 72.8, 72.3,
72.0 (5C, PhCH2), 74.4 (C-2A), 72.6 (C-2B), 71.1 (C-5A), 68.9 (C-
treated with 5.7 mL of HBF4/Et2O at rt. The solution was
stirred for 4 days. Et3N was added until neutralization and
concentrated. The residue was diluted with DCM, then washed
with satd aq NaHCO3 and water. The organic layer was dried
on MgSO4, filtered, and concentrated. The residue was eluted
from a column of silica gel with 15:1 toluene-EtOAc to give
5B), 55.3 (OCH3), 18.1 (2C, C-6A, 6B). Anal. Calcd for C50H54
-
Cl3NO10: C, 64.21; H, 5.82; N, 1.50. Found: C, 64.67; H, 6.01;
N, 1.28.
Allyl (3,4-Di-O-ben zyl-2-O-ch lor oa cetyl-r-L-r h a m n op y-
r a n osyl)-(1f2)-(3,4-d i-O-b en zyl-r-L-r h a m n op yr a n osyl)-
(1f3)-[2,3,4,6-tetr a -O-ben zyl-r-D-glu cop yr a n osyl-(1f4)]-
2-O-ben zoyl-r-L-r h a m n op yr a n osid e (38). A mixture of
alcohol 11 (212 mg, 0.255 mmol) and imidate 34 (270 mg, 0.33
mmol) in anhydrous Et2O (4 mL) was stirred for 15 min under
dry argon. After the solution was cooled at -60 °C, TMSOTf
(30 µL, 0.166 mmol) was added dropwise and the mixture was
stirred overnight and allowed to reach rt. Triethylamine (120
µL) was added and the mixture was concentrated. The residue
was eluted from a column of silica gel with 7:1 cyclohexane-
EtOAc to give 38 (86 mg, 22%) as a foam: [R]D +5 (c 1.0,
CHCl3); 1H NMR (300 MHz, CDCl3) δ 8.00-6.95 (m, 45H, Ph),
6.00-5.80 (m, 1H, All), 5.56 (dd, 1H, H-2A), 5.40 (dd, 1H, J 1,2
< 1.0 Hz, J 2,3 ) 3.0 Hz, H-2C), 5.37-5.20 (m, 2H, All), 5.08 (d,
1H, J 1,2 ) 3.2 Hz, H-1E), 5.04 (d, 1H, J 1,2 < 1.0 Hz, H-1A), 5.00
(d, 1H, J 1,2 < 1.0 Hz, H-1B), 4.99 (d, 1H, H-1C), 4.90-4.30 (m,
16H, CH2Ph), 4.35 (dd, 1H, J 2,3 ) 3.0 Hz, H-2B), 4.14 (dd, 1H,
J 3,4 ) 9.5 Hz, H-3C), 4.03 (pt, 1H, J 2,3 ) J 3,4 ) 10.0 Hz, H-3E),
4.20-3.90 (m, 2H, All), 4.00-3.75 (m, 4H, CH2Cl, H-6aE, 6bE),
3.96 (dd, 1H, H-3A), 3.95 (m, 1H, H-5A), 3.95 (m, 1H, H-5E),
3.83 (dd, 1H, H-4C), 3.80 (m, 1H, H-5C), 3.72 (dd, 1H, H-4E),
3.64 (dd, 1H, H-3B), 3.60 (m, 1H, H-5B), 3.52 (dd, 1H, H-2E),
3.39 (dd, 1H, H-4A), 3.30 (dd, 1H, H-4B), 1.35 (d, 1H, H-6A),
1.30 (d, 1H, H-6C), 1.00 (d, 1H, H-6B); 13C NMR (75 MHz,
CDCl3) δ 166.1, 165.7 (CdO), 133.4-117.0 (Ph), 100.9 (C-1B),
98.9 (C-1A), 97.8 (C-1E), 96.0 (C-1C), 81.8 (C-3E), 80.9 (C-2E),
79.9 (C-4A), 79.6 (C-4B), 79.6 (C-3C), 78.9 (C-3B), 78.0 (C-4C),
77.5 (C-4E), 77.3 (C-3A), 75.6, 75.3, 75.0, 74.7, 73.9, 73.5, 72.8,
70.9 (9C, CH2Ph, All), 74.9 (C-2B), 72.5 (C-2C), 71.2 (C-5E), 70.9
(C-2A), 68.8 (C-5B), 68.5 (C-6E), 68.3 (C-5A), 67.5 (C-5C), 40.9
(CH2Cl), 18.8 (C-6A), 18.2 (C-6C), 17.8 (C-6B). FAB-MS for
1
10 (6.31 g, 84%) as a foam: [R]D +14 (c 1.0, CHCl3); H NMR
(CDCl3) δ 8.10-7.05 (m, 35H, Ph), 5.82 (m, 1H, All), 5.25 (dd,
1H, J 1,2 ) 1.7 Hz, J 2,3 ) 3.1 Hz, H-2C), 5.19 (m, 2H, All), 5.00
(d, 1H, J 1,2 ) 3.1 Hz, H-1E), 4.87 (d, 1H, J 1,2 ) 1.8 Hz, H-1B),
4.81 (d, 1H, H-1C), 4.90-4.35 (m, 12H, CH2Ph), 4.20-4.00 (m,
2H, All), 4.10 (dd, 1H, J 3,4 ) 8.5 Hz, H-3C), 4.09 (dd, 1H, J 2,3
) 3.2 Hz, H-2B), 3.95 (m, 1H, J 4,5 ) 9.5 Hz, H-5E), 3.92 (pt,
1H, J 2,3 ) 9.5 ) J 3,4 ) 9.5 Hz, H-3E), 3.78 (dq, 1H, J 5,6 ) 6.0
Hz, H-5C), 3.70 (m, 1H, H-4C), 3.62-3.58 (m, 2H, H-6aE, 6bE),
3.59 (m, 1H, J 4,5 ) 9.0 Hz, J 5,6 ) 6.2 Hz, H-5B), 3.54 (dd, 1H,
H-4E), 3.48 (dd, 1H, J 3,4 ) 8.5 Hz, H-3B), 3.45 (dd, 1H, H-2E),
3.31 (dd, 1H, H-4B), 2.68 (d, 1H, J 2,OH ) 2.3 Hz, OH), 1.29 (d,
3H, H-6C), 1.09 (d, 3H, H-6B); 13C NMR (CDCl3) δ 166.2 (Cd
O), 137.5-118.2 (Ph, All), 103.1 (C-1B), 98.5 (C-1E), 96.6 (C-
1C), 82.1 (C-3E), 81.4 (C-2E), 80.4 (C-4B), 79.7 (C-3B), 79.4 (C-
4C), 78.9 (C-3C), 78.1 (C-4E), 76.0, 75.5, 74.5, 74.2, 73.6, 72.1
(6C, CH2Ph), 73.7 (C-2C), 71.6 (C-2B), 68.9 (C-6E), 68.8 (C-5B),
68.7 (All, C-5E), 68.1 (C-5C), 19.1 (C-6C), 18.2 (C-6B). FAB-MS
of C70H76O15 (M, 1156.5), m/z 1179.5 [M + Na]+. Anal. Calcd
for C70H76O15: C, 72.64; H, 6.62. Found: C, 72.49; H, 6.80.
Allyl (2-O-Acetyl-3,4-d i-O-ben zyl-r-L-r h a m n op yr a n o-
syl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n op yr a n osyl)-(1f3)-
[2,3,4,6-t et r a -O-b en zyl-r-D-glu cop yr a n osyl-(1f4)]-2-O-
ben zoyl-r-L-r h a m n op yr a n osid e (44). A mixture of alcohol
10 (5.2 g, 4.49 mmol), imidate 21 (3.58 g, 6.74 mmol), and 4 Å
molecular sieves in anhydrous Et2O (117 mL) was stirred for
1 h under dry argon. After the solution was cooled at -30 °C,
Me3SiOTf (580 µL, 3.2 mmol) was added dropwise and the
mixture was stirred and allowed to reach rt overnight. Tri-
ethylamine (1.2 mL) was added and the mixture was filtered
and concentrated. The residue was eluted from a column of
silica gel with 9:1 cyclohexane-EtOAc to give 44 (6.16 g, 90%)
C
92H99ClO20 (M, 1558.6) m/z 1581.7 [M + Na]+. Anal. Calcd
1
for C92H99ClO20: C, 70.82; H, 6.40. Found: C, 70.67; H, 6.58.
as a white foam: [R]D +13 (c 1.0, CHCl3); H NMR (CDCl3) δ
8.10-7.00 (m, 45H, Ph), 5.82 (m, 1H, All), 5.45 (dd, 1H, J 1,2
1.5 Hz, J 2,3 ) 2.5 Hz, H-2A), 5.29 (dd, 1H, J 1,2 ) 1.5 Hz, J 2,3
)
)
Allyl (3,4-Di-O-ben zyl-2-O-p-m eth oxyben zyl-r-L-r h a m -
n op yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n op yr a n o-
syl)-(1f3)-[2,3,4,6-t et r a -O-b en zyl-r-D-glu cop yr a n osyl-
(1f4)]-2-O-ben zoyl-r-L-r h a m n op yr a n osid e (39). A mixture
of alcohol 11 (125 mg, 0.15 mmol) and 4 Å molecular sieves in
anhydrous Et2O (3 mL) was stirred for 45 min under dry argon.
After the mixture was cooled at -40 °C, Me3SiOTf (20 µL,
0.112 mmol) was added dropwise. A solution of the donor 37
(210 mg, 0.225 mmol) in anhydrous Et2O (2 mL) was added
dropwise to the solution of the acceptor over 1 h. The mixture
was stirred for 3 h at -40 °C. Triethylamine (100 µL) was
added and the mixture was filtered and concentrated. The
residue was eluted from a column of silica gel with 85:15
cyclohexane-EtOAc to give 39 (107 mg, 44%) as a foam: [R]D
+12 (c 1.0, CHCl3); 1H NMR (CDCl3) δ 8.10-7.10 (m, 45H,
Ph), 7.00-6.50 (m, 4H, CH2PhOMe), 5.90-5.70 (m, 1H, All),
5.32 (dd, 1H, J 1,2 ) 1.6 Hz, J 2,3 ) 3.1 Hz, H-2C), 5.25-5.10 (m,
2H, All), 5.05 (d, 1H, H-1B), 4.98 (d, 1H, J 1,2 ) 3.2 Hz, H-1E),
4.85 (m, 2H, H-1A, 1C), 4.80-4.20 (m, 18H, CH2Ph), 4.20-3.90
(m, 2H, All), 4.20-3.00 (m, 20H, H-2A, 2B, 2E, 3A, 3B, 3C, 3E,
4A, 4B, 4C, 4E, 5A, 5B, 5C, 5E, 6aE, 6bE, OCH3), 1.30-0.82 (3 d,
9H, H-6A, 6B, 6C); 13C NMR (CDCl3) δ 166.3 (CdO), 138.5-
118.2 (Ph, All), 99.5, 99.3 (2C, C-1A, 1B), 98.4 (C-1E), 96.4 (C-
1C), 82.3, 81.4, 81.1, 80.5, 80.3, 79.5, 78.2, 77.6 (8C, C-2E, 3A,
3B, 3C, 3E, 4A, 4B, 4C), 76.0, 75.5, 75.3, 74.9, 74.3, 73.3, 72.3,
71.8, 71.6 (9C, CH2Ph), 74.1, 73.8 (2C, C-2A, 2B), 72.5 (C-2C),
72.0 (C-4E), 69.2, 69.0, 68.9 (3C, C-5A, 5B, 5C), 68.8, 68.6 (All,
C-6E), 67.8 (C-5E), 55.5 (OCH3), 19.0, 18.8, 18.4 (3C, C-6A, 6B,
6C). FAB-MS for C98H106O20 (M, 1603.8) m/z 1626.6 [M + Na]+.
2.5 Hz, H-2C), 5.19 (m, 2H, All), 4.97 (d, 1H, J 1,2 ) 3.2 Hz,
H-1E), 4.95 (d, 1H, H-1A), 4.91 (d, 1H, J 1,2 ) 1.6 Hz, H-1B),
4.84 (d, 1H, H-1C), 4.90-4.35 (m, 16H, CH2Ph), 4.29 (dd, 1H,
J 2,3 ) 2.6 Hz, H-2B), 4.10-4.00 (m, 2H, All), 4.02 (dd, 1H, J 3,4
) 8.5 Hz, H-3C), 3.90 (m, 2H, J 2,3 ) J 3,4 ) J 4,5 ) 9.5 Hz, H-3E,
5E), 3.85 (m, 2H, J 3,4 ) 9.3 Hz, J 4,5 ) 9.5 Hz, H-3A, 5A), 3.72
(m, 2H, J 5,6 ) 6.0 Hz, H-4C, 5C), 3.66-3.62 (m, 2H, H-6aE, 6bE),
3.61 (dd, 1H, H-4E), 3.54 (dd, 1H, J 3,4 ) 9.4 Hz, H-3B), 3.45
(dd, 1H, J 4,5 ) 9.5 Hz, J 5,6 ) 6.1 Hz, H-5B), 3.39 (dd, 1H, H-2E),
3.34 (dd, 1H, H-4A), 3.21 (dd, 1H, H-4B), 1.89 (s, 3H, OAc), 1.26
(2d, 6H, H-6A, 6C), 0.89 (d, 3H, H-6B); 13C NMR (CDCl3) δ 170.2,
166.1 (CdO), 138.4-118.1 (Ph, All), 101.3 (C-1B), 99.8 (C-1A),
98.2 (C-1E), 96.4 (C-1C), 82.2 (C-3E), 81.4 (C-2E), 80.6 (C-4A),
80.5 (C-3C), 80.1 (C-4B), 79.3 (C-3B), 78.5 (C-4C), 78.1 (C-3A),
78.0 (C-4E), 76.0, 75.9, 75.7, 75.2, 74.3, 73.3, 72.1, 71.1 (8C,
CH2Ph), 75.2 (C-2B), 72.9 (C-2C), 71.7 (C-5E), 69.5 (C-2A), 69.2
(2C, C-5A, 5B), 68.9 (All), 68.9 (C-6E), 67.9 (C-5C), 21.4 (OAc),
19.1 (C-6A), 18.7 (C-6C), 18.1 (C-6B). FAB-MS of C90H100O20 (M,
1524.7), m/z 1547.8 [M + Na]+. Anal. Calcd for C92H100O20: C,
72.42; H, 6.61. Found: C, 72.31; H, 6.75.
Allyl (3,4-Di-O-b en zyl-r-L-r h a m n op yr a n osyl)-(1f2)-
(3,4-di-O-ben zyl-r-L-r h am n opyr an osyl)-(1f3)-[2,3,4,6-tetr a-
O-b e n zyl-r-D-glu cop yr a n osyl-(1f4)]-2-O-b e n zoyl-r-L-
r h a m n op yr a n osid e (40). A mixture of 44 (6.0 g, 3.93 mmol)
in MeOH (200 mL) was treated with 10 mL of HBF4/Et2O at
rt. The solution was stirred for 5 days. Et3N was added until
neutralization and the solution was concentrated. The residue
was diluted with DCM and washed with satd aq NaHCO3 and
water. The organic layer was dried on MgSO4, filtered, and
concentrated. The residue was eluted from a column of silica
gel with 6:1 cyclohexane-EtOAc to give 40 (5.0 g, 84%) as a
Allyl (3,4-Di-O-b en zyl-r-L-r h a m n op yr a n osyl)-(1f3)-
[2,3,4,6-t et r a -O-b en zyl-r-D-glu cop yr a n osyl-(1f4)]-2-O-
ben zoyl-r-L-r h a m n op yr a n osid e (10). A mixture of the
trisaccharide 4218 (8.0 g, 6.5 mmol) in MeOH (128 mL) was
1072 J . Org. Chem., Vol. 69, No. 4, 2004

Convergent Synthesis of a Branched Decasaccharide
colorless foam: [R]D +12 (c 1.0, CHCl3); 1H NMR (CDCl3) δ
C104H114Cl3NO27: C, 65.18; H, 6.00; N, 0.73. Found: C, 64.95;
H, 6.17; N, 0.76.
8.00-7.00 (m, 45H, Ph), 5.83 (m, 1H, All), 5.29 (dd, 1H, J 1,2
)
1.8 Hz, J 2,3 ) 2.9 Hz, H-2C), 5.19 (m, 2H, All), 4.99 (d, 1H, J 1,2
) 1.4 Hz, H-1A), 4.97 (d, 1H, J 1,2 ) 3.3 Hz, H-1E), 4.94 (d, 1H,
J 1,2 ) 1.7 Hz, H-1B), 4.83 (d, 1H, H-1C), 4.90-4.35 (m, 16H,
CH2Ph), 4.30 (dd, 1H, J 2,3 ) 2.7 Hz, H-2B), 4.10-4.00 (m, 2H,
All), 4.02 (dd, 1H, J 2,3 ) 3.5 Hz, J 3,4 ) 8.5 Hz, H-3C), 3.98 (m,
1H, H-2A), 3.95-3.91 (m, 3H, H-5E, 6aE, 6aE), 3.90 (dd, 1H,
J 2,3 ) 9.5 Hz, J 3,4 ) 9.4 Hz, H-3E), 3.82-3.73 (m, 4H, H-3A, 5A,
(2,3,4-Tr i-O-a cet yl-2-d eoxy-2-t r ich lor oa cet a m id o-â-D-
glu cop yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n op yr a -
n osyl)-(1f2)-(3,4-di-O-ben zyl-r-L-r h am n opyr an osyl)-(1f3)-
[2,3,4,6-t et r a -O-b en zyl-r-D-glu cop yr a n osyl-(1f4)]-2-O-
ben zoyl-r-L-r h am n opyr an osyl Tr ich lor oacetim idate (46).
Compound 4 (3.5 g, 1.8 mmol) was dissolved in anhydrous THF
(35 mL). The solution was degassed and placed under argon.
1,5-Cyclooctadiene-bis(methyldiphenylphosphine)iridium hexa-
fluorophosphate (81 mg) was added, and the solution was
degassed again. The catalyst was activated by passing over a
stream of hydrogen until the solution turned yellow. The
reaction mixture was degassed again and stirred under an
argon atmosphere, then concentrated to dryness. The residue
was dissolved in acetone (15 mL), then water (3 mL), mercuric
chloride (490 mg), and mercuric oxide (420 mg) were added
successively. The mixture, protected from light, was stirred
at rt for 2 h and acetone was evaporated. The resulting
suspension was taken up in DCM, washed twice with 50% aq
KI, water and brine, dried, and concentrated. The residue was
eluted from a column of silica gel with 2:1 petroleum ether-
EtOAc to give the corresponding hemiacetal 45. Trichloroac-
etonitrile (6.5 mL) and DBU (97 µL) were added to a solution
of the residue in anhydrous DCM (33 mL) at 0 °C. After 1 h,
the mixture was concentrated. The residue was eluted from a
column of silica gel with 5:2 cyclohexane-EtOAc and 0.2% of
Et3N to give 46 (2.48 g, 66%) as a colorless foam: [R]D +4 (c
4C, 5C), 3.66 (dd, 1H, J 4,5 ) 9.6 Hz, H-4E), 3.53 (dd, 1H, J 3,4
)
9.5 Hz, H-3B), 3.48 (m, 1H, J 4,5 ) 9.5 Hz, H-5B), 3.44-3.40 (m,
2H, H-4A, 2E), 3.17 (pt, 1H, H-4B), 2.18 (d, 1H, J 2,OH ) 2.0 Hz,
OH), 1.26 (d, 3H, J 5,6 ) 5.5 Hz, H-6C), 1.25 (d, 3H, J 5,6 ) 6.2
Hz, H-6A), 0.90 (d, 3H, J 5,6 ) 6.2 Hz, H-6B); 13C NMR (CDCl3)
δ 166.2 (CdO), 138.3-118.0 (Ph, All), 101.5 (C-1B), 101.4 (C-
1A), 98.2 (C-1E), 96.4 (C-1C), 82.2 (C-3E), 81.4 (C-2E), 80.6 (C-
4A), 80.3 (C-4B), 79.9 (2C, C-3C, 3A), 79.2 (C-3B), 78.3 (C-4C),
78.0 (C-4E), 75.9, 75.6, 75.5, 74.8, 74.2, 73.5, 72.4, 71.0 (8C,
CH2Ph), 75.3 (C-2B), 72.9 (C-2C), 71.6 (C-2A), 69.2, 69.1, 68.3,
67.9 (4C, C-5A, 5B, 5C, 5E), 68.9, 68.7 (3C, C-6D, 6E, All), 19.1
(C-6C), 18.6 (C-6A), 18.1 (C-6B). FAB-MS of C90H98O19 (M,
1482.7), m/z 1505.8 [M + Na]+. Anal. Calcd for C90H98O19
2H2O: C, 71.12; H, 6.77. Found: C, 71.21; H, 6.78.
‚
Allyl (3,4,6-Tr i-O-a cetyl-2-d eoxy-2-tr ich lor oa ceta m id o-
â-D-glu copyr an osyl)-(1f2)-(3,4-di-O-ben zyl-r-L-r h am n opy-
r a n osyl)-(1f2)-(3,4-d i-O-b en zyl-r-L-r h a m n op yr a n osyl)-
(1f3)-[2,3,4,6-tetr a -O-ben zyl-r-D-glu cop yr a n osyl-(1f4)]-
2-O-ben zoyl-r-L-r h a m n op yr a n osid e (4). (a) A mixture of
the donor 8 (200 mg, 230 µmol) and the acceptor 10 (188 mg,
144 µmol), 4 Å molecular sieves, and dry Et2O:1,2-DCE (1:1,
5 mL) was stirred for 1.5 h then cooled to 0 °C. NIS (104 mg,
0.46 mmol) and triflic acid (4 mL, 0.05 mmol) were successively
added. The stirred mixture was allowed to reach rt in 1 h. Et3N
(25 mL) was added and the mixture filtered. After evaporation,
the residue was eluted from a column of silica gel with 4:1 to
2:1 cyclohexane-EtOAc to give 4 (28 mg, 10%).
1
1.0, CHCl3); H NMR (CDCl3) δ 8.71 (s, 1H, NH), 8.00-7.00
(m, 45H, Ph), 6.80 (d, 1H, J 2,NH ) 8.6 Hz, NHD), 6.37 (d, 1H,
J 1,2 ) 2.7 Hz, H-1C), 5.59 (dd, 1H, J 2,3 ) 2.9 Hz, H-2C), 5.10
(br s, 1H, H-1A), 5.05 (pt, 1H, J 2,3 ) 9.8 Hz, H-3D), 5.02-4.96
(m, 4H, H-1E, 1B, 4D, CH2Ph), 5.00-4.42 (m, 17H, 15 CH2Ph,
H-1D, 3C), 4.14 (br s, 1H, H-2A), 4.05-3.68 (m, 14H, H-3E, 4E,
5E, 6aE, 6bE, 4C, 5C, 2B, 3B, 3A, 5A, 2D, 6aD, 6bD), 3.61 (dq, 1H,
J 5,6 ) 6.2 Hz, J 4,5 ) 9.3 Hz, H-5B), 3.51-3.41 (m, 3H, H-2E, 4A,
5D), 3.30 (pt, 1H, J 3,4 ) J 4,5 ) 9.4 Hz, H-4B), 2.03, 2.02, 1.80
(3s, 9H, OAc), 1.39, 1.32 (2d, 6H, H-6A, 6C), 1.00 (br d, 3H,
H-6B); 13C NMR (CDCl3) δ 169.7, 169.5, 168.3, 164.5, 160.9 (Cd
O, CdN), 137.5-126.2 (Ph), 101.6 (C-1D), 101.3 (2C, C-1A, 1B),
98.7 (C-1E), 94.8 (C-1C), 91.3 (CCl3), 82.1, 81.5, 80.4, 80.1, 78.4,
77.9, 77.6, 76.5 (10C, C-2A, 2E, 3A, 3B, 3C, 3E, 4A, 4B, 4C, 4E),
76.0, 75.9, 75.5, 74.9, 74.3, 73.3 (8C, CH2Ph), 72.9, 72.6, 71.9,
70.9, 70.6, 69.1, 68.8, 68.5 (9C, C-2B, 2C, 3D, 4D, 5A, 5B, 5C, 5D,
5E), 68.3 (C-6E), 62.1 (C-6D), 56.2 (C-2D), 21.0, 20.9, 20.8 (3C,
OAc), 19.1, 18.3, 18.1 (3C, C-6A, 6B, 6C). Anal. Calcd for
(b) A mixture of alcohol 40 (5.0 g, 3.37 mmol), imidate 16
(3.0 g, 5.04 mmol), and 4 Å molecular sieves in anhydrous
DCM (120 mL) was stirred for 1 h under dry argon. After the
solution was cooled at 0 °C, TMSOTf (240 µL, 1.32 mmol) was
added dropwise and the mixture was stirred for 2.5 h while
coming back to rt. Et3N (800 µL) was added, and the mixture
was filtered and concentrated. The residue was eluted from a
column of silica gel with 4:1 to 2:1 cyclohexane-EtOAc to give
4 (6.27 g, 98%) as a colorless foam: [R]D +1.5 (c 1.0, CHCl3);
1H NMR (CDCl3) δ 8.00-7.00 (m, 45H, Ph), 6.68 (d, 1H, J 2,NH
) 8.5 Hz, NHD), 5.82 (m, 1H, All), 5.29 (dd, 1H, J 1,2 ) 1.0 Hz,
J 2,3 ) 2.3 Hz, H-2C), 5.19 (m, 2H, All), 5.00 (d, 1H, J 1,2 ) 1.0
Hz, H-1A), 4.96 (dd, 1H, J 2,3 ) 10.5 Hz, J 3,4 ) 10.5 Hz, H-3D),
4.88 (d, 1H, J 1,2 ) 3.3 Hz, H-1E), 4.85 (d, 1H, H-1C), 4.82 (d,
1H, J 1,2 ) 1.7 Hz, H-1B), 4.81 (dd, 1H, J 4,5 ) 10.0 Hz, H-4D),
4.72 (d, 1H, J 1,2 ) 8.6 Hz, H-1D), 4.90-4.35 (m, 16H, CH2Ph),
4.38 (m, 1H, H-2B), 4.10-4.00 (m, 2H, All), 4.05 (dd, 1H, J 2,3
) 2.7 Hz, H-2A), 3.95 (dd, 1H, J 2,3 ) 3.5 Hz, J 3,4 ) 8.5 Hz,
H-3C), 3.90 (m, 2H, H-5E, 4E), 3.86-3.82 (m, 2H, H-6aD, 6bD),
3.84-3.70 (m, 6H, H-3E, 6aE, 6bE, 3A, 5A, 2D), 3.68 (m, 1H,
C
103H110Cl6N2O27: C, 61.22; H, 5.49; N, 1.39. Found: C, 61.24;
H, 5.50; N, 1.21.
Meth yl (2-Deoxy-4,6-O-isop r op ylid en e-2-tr ich lor oa c-
eta m id o-â-D-glu cop yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-r-L-
r h a m n op yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n op y-
r an osyl)-(1f3)-[2,3,4,6-tetr a-O-ben zyl-r-D-glu copyr an osyl-
(1f4)]-2-O-b en zoyl-r-L-r h a m n op yr a n osid en (48). The
pentasaccharide 2 (578 mg, 0.321 mmol) was dissolved in
MeOH (10 mL). MeONa was added until pH 10. The mixture
was stirred for 25 min then treated by IR 120 (H+) until
neutral pH. The solution was filtered and concentrated. The
residue was eluted from a column of silica gel with 9:1 DCM-
MeOH to give the expected triol 47 (505 mg, 89%). To a
mixture of 47 (505 mg, 0.286 mmol) in dry DMF (2 mL) was
added 2-methoxypropene (60 µL, 2.5 equiv) and CSA (14 mg,
cat.). The mixture was stirred 1 h and Et3N (200 µL) was
added. After evaporation, the residue was eluted from a
column of silica gel with 5:2 cyclohexane-EtOAc containing
0.3% of Et3N to give 48 (420 mg, 81%) as a colorless foam: 1H
NMR (CDCl3) δ 8.00-7.00 (m, 45H, Ph), 7.17 (d, 1H, NHD),
5.39 (dd, 1H, J 1,2 ) 1.2 Hz, J 2,3 ) 3.0 Hz, H-2C), 5.13 (d, 1H,
J 1,2 ) 1.1 Hz, H-1A), 5.01 (d, 1H, J 1,2 ) 3.2 Hz, H-1E), 4.99 (d,
1H, J 1,2 ) 1.7 Hz, H-1B), 4.80 (d, 1H, H-1C), 4.70 (d, 1H, H-1D),
4.90-4.35 (m, 16H, CH2Ph), 4.40 (m, 1H, H-2B), 4.10 (dd, 1H,
H-2A), 4.05 (dd, 1H, H-3C), 4.00-3.00 (m, 20H, H-4C, 5C, 3B,
4B, 5B, 3A, 4A, 5A, 2D, 3D, 4D, 5D, 6aD, 6bD, 2E, 3E, 4E, 5E, 6aE,
H-5C), 3.61 (dd, 1H, J 4,5 ) 9.0 Hz, H-4C), 3.56 (dd, 1H, J 3,4
)
9.5 Hz, H-3B), 3.47 (m, 1H, J 4,5 ) 9.5 Hz, J 5,6 ) 6.1 Hz, H-5B),
3.35-3.33 (m, 3H, H-4A, 5D, 2E), 3.17 (dd, 1H, H-4B), 2.02, 2.00,
1.98 (3s, 9H, OAc), 1.24 (d, 3H, J 5,6 ) 6.0 Hz, H-6A), 1.23 (d,
3H, J 5,6 ) 5.9 Hz, H-6C), 0.90 (d, 3H, H-6B); 13C NMR (CDCl3)
δ 170.9, 170.7, 169.6, 166.1, 162.1 (CdO), 138.3-118.1 (Ph,
All), 101.5 (C-1D), 101.4 (C-1B), 101.1 (C-1A), 98.5 (C-1E), 96.4
(C-1C), 92.6 (CCl3), 82.1 (C-3E), 81.7 (C-3C), 81.6 (C-2E), 80.4
(C-4B), 80.1 (C-3A), 79.1 (br s, C-4C), 78.5 (C-3B), 77.9 (C-4A),
77.6 (C-4E), 76.4 (C-2A), 76.1, 75.8, 75.4, 74.7, 74.3, 74.2, 73.2,
70.4 (8C, CH2Ph), 74.9 (C-2B), 72.9 (C-3D), 72.7 (C-2C), 72.5
(C-5D), 71.9 (C-5E), 68.4 (C-6E), 68.8 (All), 68.9, 68.7, 68.5, 67.7
(4C, C-4D, 5A, 5B, 5C), 62.1 (C-6D), 56.2 (C-2D), 20.9, 20.7 (3C,
OAc), 19.0 (C-6A), 18.5 (C-6C), 18.2 (C-6B). FAB-MS of C104H114
-
Cl3NO27 (M, 1916.4), m/z 1938.9 [M + Na]+. Anal. Calcd for
J . Org. Chem, Vol. 69, No. 4, 2004 1073

Be´lot et al.
6bE), 3.40 (s, 3H, OCH3), 1.40-1.00 (m, 15H, C(CH3)2, H-6A,
6B, 6C); 13C NMR (CDCl3) partial, δ 166.2, 164.4 (CdO), 137.5-
126.5 (Ph), 101.8 (C-1D), 101.4 (C-1B), 101.2 (C-1A), 100.2
(C(CH3)2), 98.4 (C-1E), 98.2 (C-1C), 92.4 (CCl3), 68.5 (C-6E), 61.8
(C-6D), 60.1 (C-2D), 55.5 (OCH3), 29.3, 19.4 (C(CH3)2), 19.1, 18.6,
18.2 (C-6A, 6B, 6C). FAB-MS of C99H110Cl3N1O24 (M, 1804.1),
m/z 1827.0 [M + Na]+. Anal. Calcd for C99H110Cl3N1O24: C,
65.90; H, 6.15; N, 0.78. Found: C, 65.89; H, 6.29; N, 0.68.
Met h yl (3,4,6-Tr i-O-a cet yl-2-d eoxy-2-t r ich lor oa cet a -
m ido-â-D-glu copyr an osyl)-(1f2)-(3,4-di-O-ben zyl-r-L-r h am -
n op yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-r-L-r h a m n op yr a n o-
syl)-(1f3)-[2,3,4,6-t et r a -O-b en zyl-r-D-glu cop yr a n osyl-
(1f4)]-(2-O-ben zoyl-r-L-r h am n opyr an osyl)-(1f3)-(2-deoxy-
2-tr ich lor oa ceta m id o-â-D-glu cop yr a n osyl)-(1f2)-(3,4-d i-
O-ben zyl-r-L-r h a m n op yr a n osyl)-(1f2)-(3,4-d i-O-ben zyl-
r-L-r h a m n op yr a n osyl)-(1f3)-[2,3,4,6-tetr a -O-ben zyl-r-D-
g lu c o p y r a n o s y l-(1f4)]-2-O -b e n zo y l-r-L -r h a m n o p y r -
a n osid e (50). A mixture of 46 (154 mg, 76 µmol) and 48 (92
mg, 51 µmol), 4 Å molecular sieves, and dry 1,2-DCE (3 mL)
was stirred for 1 h, then cooled to -35 °C. Triflic acid (6 µL)
was added. The stirred mixture was allowed to reach 10 °C in
2.5 h. Et3N (25 µL) was added and the mixture was filtered.
After evaporation, the residue was eluted from a column of
silica gel with 2:1 cyclohexane-EtOAc containing 0.5% of Et3N
to give 49 (186 mg) as a contaminated material. To a solution
of the isolated contaminated 49 (186 mg) in DCM (3 mL) was
added dropwise, at 0 °C, a solution of TFA (0.5 mL) and water
(0.5 mL). The mixture was stirred for 3 h, then concentrated
by coevaporation with water then toluene. The residue was
eluted from a column of silica gel with 2:1 to 1:1 petroleum
ether-EtOAc to give 50 (134 mg, 72%, 2 steps) as a white
solid: [R]D +6 (c 1.0, CHCl3); 1H NMR (CDCl3) δ 8.05-7.10
(m, 90H, Ph), 6.86-6.82 (2d, 2H, J 2,NH ) 8.0 Hz, J 2,NH ) 8.5
Hz, NHD, NHD′), 5.35-5.19 (m, 2H, H-2C, 2C′), 5.20, 5.08 (2s,
2H, H-1A, 1A′), 5.05 (dd, 1H, H-3D′), 4.99-4.80 (m, 9H, H-1B,
1B′, 1C, 1C′, 1D, 1D′, 1E, 1E′, 4D′), 4.80-4.30 (m, 32H, OCH2Ph),
4.10-3.15 (m, 44H, H-2A, 2A′, 2B, 2B′, 2D, 2D′, 2E, 2E′, 3A, 3A′, 3B,
3B′, 3C, 3C′, 3D, 3E, 3E′, 4A, 4A′, 4B, 4B′, 4C, 4C′, 4D, 4E, 4E′, 5A, 5A′,
5B, 5B′, 5C, 5C′, 5D, 5D′, 5E, 5E′, 6aD, 6bD, 6aD′, 6bD′, 6aE, 6bE, 6aE′,
6bE′), 3.42 (3H, s, OMe), 2.08, 2.04, 2.02 (9H, 3s, OAc), 1.40-
0.96 (18H, m, H-6A, 6A′, 6B, 6B′, 6C, 6C′); 13C NMR (CDCl3) δδ
171.5, 170.9, 170.8, 169.6, 166.2, 162.4, 162.1 (CdO), 139.5-
127.2 (Ph), 101.9, 101.6, 101.5, 101.3, 99.2, 98.8, 98.2 (10C,
C-1A, 1A′, 1B, 1B′, 1C, 1C′, 1D, 1D′, 1E, 1E′), 92.7, 92.6 (2C, CCl3),
82.1, 81.8, 81.7, 80.5, 80.3, 80.1, 79.3, 77.9, 77.8, 73.0, 72.6,
72.5, 72.0, 69.4, 69.0, 68.9, 67.4 (39C, C-2A, 2A′, 2B, 2B′, 2C, 2C′,
2E, 2E′, 3A, 3A′, 3B, 3B′, 3C, 3C′, 3D, 3D′, 3E, 3E′, 4A, 4A′, 4B, 4B′, 4C,
4C′, 4D, 4D′, 4E, 4E′, 5A, 5A′, 5B, 5B′, 5C, 5C′, 5D, 5D′, 5E, 5E′, 6D′),
76.0, 75.9, 74.8, 74.3, 73.6, 73.2, 68.6 (CH2Ph), 62.3, 62.2, 60.7
(3C, C-6D, 6E, 6E′), 55.5, 56.2 (3C, C-2D, 2D′, OCH3), 21.0, 20.9,
20.8 (OAc), 19.0, 18.7, 18.6, 18.2, 17.9 (6C, C-6A, 6A′, 6B, 6B′,
6C, 6C′). FAB-MS for C197H214Cl6N2O50 (M, 3622.5), m/z 3645.3
[M + Na]+. Anal. Calcd for C197H214Cl6N2O50: C, 65.32; H, 5.95;
N, 0.77. Found: C, 65.20; H, 6.03; N, 0.78.
(1f3)-(2-a ceta m id o-2-d eoxy-â-D-glu cop yr a n osyl)-(1f2)-
(r-L-r h a m n op yr a n osyl)-(1f2)-(r-L-r h a m n op yr -a n osyl)-
(1f3)-[r-D -g lu c o p y r a n o s y l-(1f4)]-r-L -r h a m n o -p y r -
a n osid e (1). A solution of 50 (183 mg, 50 µmol) in EtOH (3
mL), EtOAc (0.3 mL), and 1 M HCl (100 µL) was hydrogenated
in the presence of Pd/C (250 mg) for 72 h at rt. The mixture
was filtered and concentrated. A solution of the residue in
MeOH (4 mL) and Et3N (200 µL) was hydrogenated in the
presence of Pd/C (200 mg) for 24 h at rt. The mixture was
filtered and concentrated. A solution of the residue (50 mg,
25 µmol) in MeOH (3 mL) and DCM (0.5 mL) was treated by
MeONa until pH 10. The mixture was stirred overnight at 55
°C. After the solution was cooled at rt, IR 120 (H+) was added
until neutral pH, and the solution was filtered and concen-
trated, then was eluted from a column of C-18 with water/
CH3CN and freeze-dried to afford amorphous 1 (30 mg, 37%):
1
[R]D -1 (c 1.0, H2O); H NMR (D2O) δ 5.13 (2d, 2H, J 1,2 ) 3.5
Hz, H-1E, 1E′), 5.05, 4.95, 4.75 (m, 5H, H-1A, 1B, 1A′, 1B′, 1C′),
4.64-4.62 (2d, 2H, J 1,2 ) 7.0 Hz, J 1,2 ) 8.0 Hz, H-1D, 1D′), 4.58
(d, 1H, J 1,2 ) 2.2 Hz, H-1C), 4.10-3.20 (m, 51H, H-2A, 2A′, 2B,
2B′, 2C, 2C′, 2D, 2D′, 2E, 2E′, 3A, 3A′, 3B, 3B′, 3C, 3C′, 3D, 3D′, 3E, 3E′,
4A, 4A′, 4B, 4B′, 4C, 4C′, 4D, 4D′, 4E, 4E′, 5A, 5A′, 5B, 5B′, 5C, 5C′, 5D,
5D′, 5E, 5E′, 6aD, 6bD, 6aD′, 6bD′, 6aE, 6bE, 6aE′, 6bE′, OCH3), 1.99,
1.97 (2s, 6H, 2 NHAc), 1.33-1.15 (6d, 18H, J 5,6 ) 6.3 Hz, H-6A,
6B, 6C, 6A′, 6B′, 6C′); 13C NMR (D2O) δδ 175.2, 174.7 (CdO), 103.1
(2C, C-1D′, 1D), 102.6, 101.7, 101.3, 100.8 (6C, C-1A, 1B, 1C, 1A′,
1B′, 1C′), 98.0 (2C, C-1E, 1E′), 81.6, 79.7, 79.6, 79.1, 76.2, 76.1,
73.9, 73.0, 72.7, 72.6, 72.5, 72.2, 72.1, 71.6, 70.1, 70.0, 69.7,
69.0, 68.5 (38C, C-2A, 2A′, 2B, 2B′, 2C, 2C′, 2E, 2E′, 3A, 3A′, 3B, 3B′,
3C, 3C′, 3D, 3D′, 3E, 3E′, 4A, 4A′, 4B, 4B′, 4C, 4C′, 4D, 4D′, 4E, 4E′, 5A,
5A′, 5B, 5B′, 5C, 5C′, 5D, 5D′, 5E, 5E′), 60.9 (4C, C-6E, 6E′, 6D, 6D′),
56.2, 56.0, 55.3 (3C, C-2D, 2D′, OCH3), 22.7, 22.6 (2C, NHAc),
18.3, 18.1, 17.2, 17.1, 17.0, 16.9 (6C, C-6A, 6B, 6C, 6A′, 6B′, 6C′).
HR-MS calcd for [C65H110N2O45 + Na]+ 1661.6278, found
1661.6277.
Ack n ow led gm en t. The authors thank Pr. P. J .
Sansonetti (Unite´ de Pathoge´nie Microbienne Mole´cu-
laire, Institut Pasteur), who is a scholar of the Howard
Hughes Medical Institute, for his key input in the
project. The authors are grateful to J . Ughetto-Monfrin
(Unite´ de Chimie Organique, Institut Pasteur) for
recording all the NMR spectra. The authors thank the
CANAM and the Fondation pour la Recherche Me´dicale
(Ph.D fellowship to C.C.), the Bourses Mrs Frank
Howard Foundation for its postdoctoral fellowship to
K.W. and financial support, as well as the Bourses Roux
foundation (postdoctoral fellowship to F.B.).
Su p p or tin g In for m a tion Ava ila ble: 1H, 13C, and DEPT
1
1
1D NMR spectra and H-1H and H-13C 2D NMR correlation
spectra of compounds 1, 4-8, 10, 17-20, 22-23, 25, 32-34,
39, 44, 46, 48, and 50. This material is available free of charge
via the Internet at http://pubs.acs.org.
Meth yl (2-Aceta m id o-2-d eoxy-â-D-glu cop yr a n osyl)-(1f
2)-(r-L-r h a m n op yr a n osyl)-(1f2)-(r-L-r h a m n op yr a n osyl)-
(1f3)-[r-D-glu copyr an osyl-(1f4)]-(r-L-r h am n opyr an osyl)-
J O035125B
1074 J . Org. Chem., Vol. 69, No. 4, 2004