Linear total synthetic routes to β-D-C-(1,6)-linked oligoglucoses and oligogalactoses up to pentaoses by iterative Wittig olefination assembly

Article abstract of DOI:10.1021/jo011142u

Two complementary routes, A and B, have been followed for the stepwise iterative assembly of β-D-(1,6)-glucopyranose and galactopyranose residues through methylene bridges. In route A the building block was constituted by 2,3,4-tri-O-benzyl-6-O-tert-butyldiphenylsilyl (O-TBDPS) β-linked galactosylmethylenephosphorane, while in route B the building block was a β-linked formyl C-glycopyranoside with a similar orthogonal protection of hydroxy groups. In route A each cycle consisted of the reaction of the phosphorane building block with a sugar residue bearing a formyl group at the C-5 carbon atom (coupling) and transformation of the O-TBDPS-protected primary alcohol into the formyl group (arming). Accordingly, route A is defined as the aldehyde route. On the other hand, each cycle in route B involved the coupling of the sugar aldehyde building block with a substrate bearing a phosphorus ylide at C-6 and introduction of the phosphonium group in the arming step as a precursor of the ylide functionality. Accordingly, route B is defined as the ylide route. The efficiency of route A proved to be seriously hampered by the 1,2-elimination of BnOH under the basic reaction conditions of the Wittig olefination, giving rise to the formation of substantial amounts of enopyranose. On the other hand, the ylide route B proved to be more efficient since very good yields (70-93%) of the isolated Wittig products were obtained throughout four consecutive cycles. Individual olefins and polyolefins obtained by routes A and B using gluco and galacto substrates were reduced and debenzylated in one pot by H₂/Pd(OH)₂ to give the corresponding β-D-C-(1,6)-linked oligosaccharides up to the pentaose stage. The latter compounds were fully characterized by high-field NMR spectroscopy (500 MHz).

Full text of DOI:10.1021/jo011142u

4186
J . Org. Chem. 2002, 67, 4186-4199
Lin ea r Tota l Syn th etic Rou tes to â-D-C-(1,6)-Lin k ed Oligoglu coses
a n d Oligoga la ctoses u p to P en ta oses by Iter a tive Wittig
Olefin a tion Assem bly†
Alessandro Dondoni,* Alberto Marra, Mamoru Mizuno,‡ and Pier Paolo Giovannini
Laboratorio di Chimica Organica, Dipartimento di Chimica, Universita` di Ferrara,
Via Borsari 46, 44100 Ferrara, Italy
adn@dns.unife.it
Received December 13, 2001
Two complementary routes, A and B, have been followed for the stepwise iterative assembly of
â-D-(1,6)-glucopyranose and galactopyranose residues through methylene bridges. In route A the
building block was constituted by 2,3,4-tri-O-benzyl-6-O-tert-butyldiphenylsilyl (O-TBDPS) â-linked
galactosylmethylenephosphorane, while in route B the building block was a â-linked formyl
C-glycopyranoside with a similar orthogonal protection of hydroxy groups. In route A each cycle
consisted of the reaction of the phosphorane building block with a sugar residue bearing a formyl
group at the C-5 carbon atom (coupling) and transformation of the O-TBDPS-protected primary
alcohol into the formyl group (arming). Accordingly, route A is defined as the aldehyde route. On
the other hand, each cycle in route B involved the coupling of the sugar aldehyde building block
with a substrate bearing a phosphorus ylide at C-6 and introduction of the phosphonium group in
the arming step as a precursor of the ylide functionality. Accordingly, route B is defined as the
ylide route. The efficiency of route A proved to be seriously hampered by the 1,2-elimination of
BnOH under the basic reaction conditions of the Wittig olefination, giving rise to the formation of
substantial amounts of enopyranose. On the other hand, the ylide route B proved to be more efficient
since very good yields (70-93%) of the isolated Wittig products were obtained throughout four
consecutive cycles. Individual olefins and polyolefins obtained by routes A and B using gluco and
galacto substrates were reduced and debenzylated in one pot by H2/Pd(OH)2 to give the
corresponding â-D-C-(1,6)-linked oligosaccharides up to the pentaose stage. The latter compounds
were fully characterized by high-field NMR spectroscopy (500 MHz).
In tr od u ction
into the mechanism of glycoside elaboration by carbohy-
drate-processing enzymes. In turn glycomimetics may
become effective inhibitors of those enzymes and there-
fore evolve into lead compounds of pharmaceutical rel-
evance. The simplest modification that can be made in
natural oligosaccharides and glycoconjugates to obtain
chemically and enzymatically resistant analogues is the
replacement of the oxygen atom of the glycosidic linkage
with a methylene group. Many synthetic approaches to
these analogues have therefore been devised, most of
which have been restricted to C-disaccharides.5 Only in
recent years increasing attention has been addressed to
Oligosaccharides and glycoconjugates deeply influence
many fundamental biological processes in living organ-
isms.1 They mediate a variety of events, including
inflammation, immunological response, fertilization, can-
cer metastasis, and viral and bacterial infection.2 Hence,
there is a great need for usable quantities of natural
carbohydrates with a well-defined structure and compo-
sition for biological studies aiming at a better under-
standing of those phenomena at the molecular level.
Given the intrinsic difficulty to obtain complex natural
oligosaccharides and glycoconjugates in a pure and
homogeneous form from natural sources because of the
presence of mixtures of glycosylated species (glycoforms),
a major opportunity is provided by chemical synthesis.3
Complementary synthetic efforts must also be directed
toward the supply of structurally modified sugar-contain-
ing molecules, the so-called glycomimetics,4 which may
serve as tools for studying conformational preferences of
their parent natural products as well as probes of
recognition specificity, and may provide important insight
(3) (a) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155-
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4393. (j) J ung, K. H.; Mu¨ller, M.; Schmidt, R. R. Chem. Rev. 2000,
100, 4423-4442. (l) Hanessian, S.; Lou, B. Chem. Rev. 2000, 100,
4443-4463. (m) Koeller, K. M.; Wong, C.-H. Chem. Rev. 2000, 100,
4465-4493. (n) Danishefsky, S. J .; Allen, J . R. Angew. Chem., Int. Ed.
2000, 39, 836-863. (o) Nicolau, K. C.; Mitchell, H. J . Angew. Chem.,
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† Dedicated to Professor Albert I. Mayers.
‡ On temporary leave from the Noguchi Institute, Tokyo, J apan.
(1) (a) Varki, A. Glycobiology 1993, 3, 97-130. (b) Lee, Y. C.; Lee,
R. T. Acc. Chem. Res. 1995, 28, 321-327. (c) Dwek, R. A. Chem. Rev.
1996, 96, 683-720. (d) Bertozzi, C. R.; Kiessling, L. L. Science 2001,
291, 2357-2364.
(4) Although it has been recently pointed out that a strict definition
of the term glycomimetic has not yet been made (Patel, A.; Lindorst,
T. K. J . Org. Chem. 2001, 66, 2674-2680), this issue has been
addressed in earlier publications: (a) Hanessian, S.; Prabhanjan, H.
Synlett 1994, 868-870. (b) Sears, P.; Wong, C.-H. Angew. Chem., Int.
Ed. 1999, 38, 2300-2324.
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10.1021/jo011142u CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/17/2002

Synthesis of Oligoglucoses and Oligogalactoses
J . Org. Chem., Vol. 67, No. 12, 2002 4187
olefination strategy, which allowed us to prepare for the
first time a carbon-linked pentasaccharide of this class
of carbohydrate mimics.14 Following these preliminary
reports, we describe here in full view the implementation
of our iterative strategy.
Resu lts a n d Discu ssion
Syn th etic P la n n in g. Our intention in the present
work was the achievement of an iterative assembly of
carbohydrate units through methylene bridges holding
the C-1 of one residue and the C-6 of the other. This
accomplishment had to be accompanied by full stereo-
chemical control to give exclusively a â-D-linkage to the
C-1 carbon atom. Guided by the earlier experience that
we acquired in the synthesis of C-(1,6)-disaccharides5a as
well as in the related work regarding the preparation of
C-glycosyl amino acids15 via Wittig olefination, it seemed
logical to adopt the same synthetic strategy by a suitable
adjustment of the tactic. To this aim we envisaged two
possible routes (Scheme 1). Route A employs as a building
block a sugar derivative, A, carrying a methylenephos-
phonium group at C-1 and a differentially protected
hydroxyl group at C-6. The initial base-promoted reaction
of A with the sugar aldehyde B would lead to the olefin
C (coupling). This can be transformed into the aldehyde
D (arming), which in turn will be subjected to the
coupling with A to start the second cycle of the iterative
process. Route B employs as a building block a suitably
protected formyl C-glycoside, E, which in the first cycle
is coupled with a glycopyranose 6-phosphorane derived
from the phosphonium species F . The resulting olefin C
would be transformed into the phosphonium salt G,
which in turn will be subjected to the subsequent
olefination with E to start a second cycle. Quite evidently,
since the same identical coupling product C is obtained
by the two routes, one should be able to switch from one
route to the other as may be required. Each cycle can be
interrupted at the level of the coupling product whose
double bond(s) can be reduced to give the target dimer,
trimer, and so on.
Syn th esis of th e Bu ild in g Block s. Quite crucial in
both routes was the efficient and fast regeneration of the
reactive functional group in the arming step, i.e., the
formyl group in route A and the phosphorus ylide in route
B. This operation appeared to be finalized by an orthogo-
nal protection of the hydroxy groups in the building block
types A and E. To this aim it was decided to use the
benzyl group and the tert-butyldiphenylsilyl group to
differentiate the secondary from the primary hydroxy
groups. The synthesis of these building blocks involved
common intermediates as shown in Scheme 2 starting
from a sugar lactone. In particular the galactonolactone
1 was allowed to react with 2-lithiobenzothiazole16 (2) to
give the corresponding ketose 3, which following activa-
tion to the O-acetate 4 was deoxygenated to the ben-
zothiazolyl C-glycoside 5. The selective removal of the
O-benzyl group from the primary alcohol via acetolysis
and transesterification, followed by silylation with tert-
butyldiphenylsilyl chloride, afforded the differentially
hydroxy-protected glycoside 6. The application of the
F igu r e 1. â-D-(1,6)-Ga la cta n s (X ) O) a n d m eth ylen e
isoster es (X ) CH2).
the synthetic challenge of preparing higher oligomers.
Thus, engaged with their NMR studies on the preference
of the C-glycosidic bond for the exo-anomeric conforma-
tion, Kishi and co-workers described the synthesis of
various C-trisaccharides with 1,2 and 1,4 methylene
bridges.6 Sutherlin and Armstrong prepared a collection
of 12 stereochemically and structurally diverse C-trisac-
charides as potential inhibitors for the cell surface
proteins of the bacterium Helicobacter pylori,7 a pathogen
associated with gastritis and peptic ulcers and implicated
in gastric carcinoma. Skrydstrup and co-workers reported
the synthesis of a branched C-trisaccharide analogue of
the high-mannose core which is present in asparagine-
linked oligosaccharides.8 Also the preparations of mixed
O,C-trisaccharides have been carried out in the labora-
tories of Sinay¨ (O,C-analogue of the Lewisx trisaccharide)9
and Martin (O,C-analogue of methyl 4′-O-â-D-glucopyra-
nosylgentiobioside).10 Quite recently, we11 and Sinay¨ and
co-workers12 developed iterative synthetic protocols based
on Wittig olefination and sugar lactone-alkyne coupling,
respectively, which afforded â-D-C-(1,6)-oligogalactosides
up to the tetrasaccharide term. These works provided the
first totally synthetic route to tetrasaccharide methylene
isosteres of â-D-(1,6)-galactans, which have been shown
by Glaudemans to bind to various monoclonal immuno-
globulins13 (Figure 1). Subsequently we have developed
an improved synthetic protocol yet based on a Wittig
(5) (a) Dondoni, A.; Zuurmond, H. M.; Boscarato A. J . Org. Chem.
1997, 62, 8114-8124. (b) Rubinstenn, G.; Esnault, J .; Mallet, J .-M.;
Sinay¨, P. Tetrahedron: Asymmetry 1997, 8, 1327-1336. (c) Andersen,
L.; Mikkelsen, L. M.; Beau, J .-M.; Skrydstrup, T. Synlett 1998, 1393-
1395. (d) Ravishankar, R.; Surolia, A.; Vijayan, M.; Lim, S.; Kishi, Y.
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Polat, T.; Linhardt, R. J . J . Org. Chem. 1999, 64, 7254-7259. (f)
J arreton, O.; Skrydstrup, T.; Espinosa, J .-F.; J ime´nez-Barbero, Beau,
J .-M. Chem. Eur. J . 1999, 5, 430-441. (g) Postema, M. H. D.;
Calimente, D. Tetrahedron Lett. 1999, 40, 4755-4759. (h) Griffin, F.
K.; Paterson, D. E.; Taylor, R. J . K. Angew. Chem., Int. Ed. 1999, 38,
2939-2942. (i) Roy, R.; Dominique, R.; Das, S. K. J . Org. Chem. 1999,
64, 5408-5412. (j) Bazin, H. G.; Du, Y., Polat, T.; Linhardt, R. J . J .
Org. Chem. 1999, 64, 7254-7259. (k) Zhu, Y.-H.; Demange, R.; Vogel,
P. Tetrahedron: Asymmetry 2000, 11, 263-282. (l) Pasquarello, C.;
Picasso, S.; Demange, R.; Malissard, M.; Berger, E. G.; Vogel, P. J .
Org. Chem. 2000, 65, 4251-4260. (m) Postema, M. H. D.; Calimente,
D.; Liu, L.; Behrmann, T. L. J . Org. Chem. 2000, 65, 6061-6068. (n)
Zhu, Y.-H.; Vogel, P. Synlett 2001, 79-81. (o) Harding, M.; Nelson, A.
Chem. Commun. 2001, 695-696.
(6) (a) Haneda, T.; Goekjian, P. G.; Kim, S. H.; Kishi, Y. J . Org.
Chem. 1992, 57, 490-498. (b) Wei, A.; Haudrechy, A.; Audin, C.; J un,
H.-S.; Haudrechy-Bretel, N.; Kishi, Y. J . Org. Chem. 1995, 60, 2160-
2169.
(7) Sutherlin, D. P.; Armstrong, R. W. J . Org. Chem. 1997, 62, 5267-
5283.
(8) Mikkelsen, L. M.; Krintel, S. L.; J ime´nez-Barbero, J .; Skrydstrup,
T. Chem. Commun. 2000, 2319-2320.
(9) Berthault, P.; Birlirakis, N.; Rubistenn, G.; Sinay¨, P. J . Biomol.
NMR 1996, 8, 23-35.
(10) Spak, S. J .; Martin, O. Tetrahedron 2000, 56, 217-224.
(11) Dondoni, A.; Kleban, M.; Zuurmond, H.; Marra, A. Tetrahedron
Lett. 1998, 39, 7991-7994.
(14) Dondoni, A.; Mizuno, M.; Marra, A. Tetrahedron Lett. 2000, 41,
6657-6660.
(12) Xin, Y.-C.; Zhang, Y.-M.; Mallet, J .-M.; Glaudemans, C. P. J .;
Sinay¨, P. Eur. J . Org. Chem. 1999, 471-476.
(15) (a) Dondoni, A.; Marra, A.; Massi, A. Tetrahedron 1998, 54,
2827-2832. (b) Dondoni, A.; Marra, A. Chem. Rev. 2000, 100, 4395-
4421.
(13) Glaudemans, C. P. J . Chem. Rev. 1991, 91, 25-33.

4188 J . Org. Chem., Vol. 67, No. 12, 2002
Dondoni et al.
Sch em e 1
Sch em e 2a
formyl group in the arming step (C to D in Scheme 1).
Hence, the ylide generated from the phosphonium iodide
8 by treatment with BuLi at -50 °C in THF-HMPA (3:
1) was allowed to react with an excess of the readily
available galactose-derived aldehyde 9 according to our
earlier protocol5a to give the olefin 10 (mixture of E,Z
isomers) in very good yield (70%) (Scheme 3). Then, the
silyl protective group was removed and the primary
alcohol was oxidized to the aldehyde 11 in excellent
overall yield (70%). Treatment of this aldehyde with the
ylide of 8 generated as described above revealed the
existence of a serious problem in this approach since the
desired trisglycosylated bisolefin 12 was isolated in only
36% yield while a side product, 12a (Chart 1), featuring
an endocyclic double bond in one pyranose ring was
formed in almost comparable amount. This problem
became even more dramatic in the subsequent cycle
because the side product 14a was isolated in much higher
yield (28%) than the desired product 14 (11%). It seems
logical to suggest that 12a and 14a are formed by the
coupling of the ylide derived from 8 with the enals arising
from 11 and 13 by elimination of a molecule of benzyl
alcohol. This elimination is due to the basic medium
required for the generation of the ylide and by the ylide
itself, causing abstraction of the proton at the R-position
adjacent to the formyl group. Evidently, this reaction
becomes more substantial when the rate of the aldehyde
coupling with the phosphorus ylide diminishes as a
consequence of the increase of the complexity of the
system. It should be noted that the elimination reaction
should be especially favored in the case of C-5 formyl
galactopyranose derivatives due to the 1,2-transdiaxial
arrangement of the hydrogen atom and the C-4 benzyloxy
group. It is worth noting that we observed a competing
E2 reaction also in the Wittig coupling of a sugar
phosphorane with a formyl â-D-C-mannopyranoside, an
aldehyde featuring the same stereochemical arrangement
of the R-hydrogen atom and the adjacent benzyloxy
group.5a The elimination of benzyl alcohol from sugar-
based aldehydes under the conditions of Wittig reactions
has been reported in other instances.17 Nevertheless,
despite the low efficiency of the strategy, the olefins 10,
a
BTh ) 2-benzothiazolyl.
formyl unmasking protocol to 6 under the conditions
required by the benzothiazole ring16 produced the formyl
C-galactoside 7, the first target building block. The
conversion of the latter into the galactosylmethylene-
phosphonium iodide 8, the second building block, was
carried out by elaboration of the formyl group via
reduction to alcohol (NaBH4), iodination (I2, PPh3), and
phosphanation (PPh3).
Ald eh yd e Rou te A. We first considered route A more
attractive than route B because of the straightforward
transformation of the primary hydroxy group into the
(16) Extensive work in our laboratory has been dealing with the
use of thiazole as formyl protective group (Dondoni, A. Synthesis 1998,
1681-1706). However, the replacement of thiazole with benzothiazole
in the synthesis of formyl C-glycosides gives rise to considerable
economical advantages and produces, in many cases, crystalline
compounds which can be more easily purified and handled. The crucial
step with the use of benzothiazole remains its cleavage to the formyl
group. In particular the hydrolysis of the benzothiazoline in the final
step of the unmasking process requires the assistance of silver ion to
obtain a good yield of aldehyde.
(17) (a) Nicotra, F.; Ronchetti, F.; Russo, G.; Toma, L. Tetrahedron
Lett. 1984, 25, 5697-5700. (b) Fre´chou, C.; Dheilly, L.; Beaupe`re, D.;
Uzan, R.; Demailly, G. Tetrahedron Lett. 1992, 33, 5067-5070. (c)
Heras-Lo´pez, A. M.; Pino-Gonza´lez, M. S.; Sarabia-Garc´ıa, F.; Lo´pez-
Herrera, F. J . J . Org. Chem. 1998, 63, 9630-9634.

Synthesis of Oligoglucoses and Oligogalactoses
J . Org. Chem., Vol. 67, No. 12, 2002 4189
Sch em e 3
Ch a r t 1
Ch a r t 2
12, and 14 were transformed into the corresponding â-D-
C-(1,6)-linked oligogalactoses 15, 16, and 17 via treat-
ment with H2/Pd(OH)2 (Chart 2). All compounds were
characterized through their O-acetyl derivatives.
(120 °C, 3 days) as we reported earlier5a for the prepara-
tion of the corresponding gluco derivative 21. Hence, also
this compound whose use will be described later on in
this work was prepared in a similar way as shown in
Scheme 4.
Not surprisingly the coupling of the excess aldehyde 7
with the ylide generated from the phosphonium salt 20
under the usual conditions (BuLi in THF-HMPA at -20
°C) afforded the corresponding bisglycosylated olefin 22
in very good yield (81%) (Scheme 5). The preservation of
the original configuration at C-5 and C-8 in 22 was
confirmed by the J 8,9 value of 9.3 Hz, in agreement with
a â-D-linkage at the anomeric center of one sugar residue
Ylid e Rou te B. We next turned to this route with
some confidence because some earlier experiments showed
the lack of substantial benzylic elimination.11 While the
aldehyde building block 7 was available via the reaction
sequence shown in Scheme 2, the substrate phosphonium
salt 20, which was required in the first cycle of this route,
was prepared by coupling the iodogalactose 18 with neat
triphenylphosphine at 120 °C (Scheme 4). These solvent-
free conditions gave the target product in much higher
yield and shorter reaction time than those employing a
solution of triphenylphosphine in tetramethylenesulfolane

4190 J . Org. Chem., Vol. 67, No. 12, 2002
Dondoni et al.
Sch em e 4a
tained in a way similar to that of the C-galactoside
derivative 7 (see Scheme 2) via the benzothiazole-based
formylation technique of the gluconolactone 33 through
the benzothiazolyl C-glucoside intermediates 34 and 35
(Scheme 6).
The construction of the sugar-olefin chain was carried
out using the same coupling-arming sequence described
above in the galacto series. Scheme 7 shows details of
this stepwise oligomerization in which very good yields
of products were obtained both in the Wittig olefination
step (70-84%) and in the installation of the phosphonium
group (56-73%) over four consecutive cycles. Also in this
case it was carefully ascertained by NMR analysis of the
first adduct 37 that the â-D-linkage was preserved in one
sugar moiety (J 8,9 ) 9.0 Hz) as well as the D-gluco
configuration in the other sugar residue (J 4,5 ) 10.0 Hz).
The sugar olefin 37 and the polyolefins 39, 41, and 43
were transformed via desilylation and hydrogenation into
the corresponding C-(1,6)-linked glucose di-, tri-, tetra-,
and pentasaccharides 44-47 (Chart 4). All of these
compounds were isolated and characterized as their
O-acetyl derivatives. In particular the acetate of the
glucopentaose 47, which was analyzed by 500 MHz NMR
spectroscopy, showed large coupling constant values
between the H-1 and H-2 (9.5-9.9 Hz) as well as the H-4
and H-5 protons (9.6-10.1 Hz) of the B-E moieties.
These values indicated a transdiaxial arrangement of the
above-mentioned protons and therefore a â-D-gluco con-
figuration for the B-E sugar units.
In conclusion, a novel and reasonably efficient method
for the synthesis of artificial carbon-linked (1,6)-oligosac-
charides has been developed and its scope demonstrated
by the synthesis of di-, tri-, tetra-, and pentagalacto and
-gluco oligomers. The high yields registered over four
consecutive cycles indicated the possibility of access to
higher oligomers. Moreover, the method should be ex-
tensible to other sugars and readily adaptable to tech-
niques using solid supports or polymer-supported re-
agents.
a
Key: 18, 20, R1 ) OBn, R2 ) H (galacto series); 19, 21, R1
)
H, R2 ) OBn (gluco series).
and the J 4,5 value of 0.8 Hz consistent with the D-galacto
configuration in the other moiety. Moreover, the subse-
quent arming step requiring the installation of the
phosphonium group via desilylation (Bu4NF), iodination
(I2, PPh3), and phosphanation (PPh3) turned out to be a
quite effective operation, affording the sugar phospho-
nium iodide 23 in excellent yield (88%). Quite reward-
ingly, and with elimination of our anxiety, the corre-
sponding ylide coupled with the aldehyde 7 to give the
bisolefin 24 in similarly high yield (87%) without any
substantial side product formation. A similar satisfactory
scenario appeared in two subsequent cycles, both being
characterized by a high-yield arming sequence and Wittig
olefination, the latter step leading to the sugar polyolefins
26 and 28 in excellent yields (93 and 92%). After having
removed the silyl protective group from compounds 22,
24, 26, and 28, we could reductively debenzylate and
saturate the double bond(s) by catalytic hydrogenation
to give the â-C-(1,6)-linked oligogalactoses 29-32 (Chart
3). The complete assignment of the proton signals of the
O-acetyl derivative of the galactopentaose 32 by NMR
analysis at 500 MHz confirmed the â-D-linkage at the
anomeric center of the carbohydrate units B-E, since a
J
1,2 value of 9.3 Hz was observed in each case. Moreover,
ROESY experiments indicated a cis-relationship between
the H-5 and H-3 protons of all monosaccharide residues,
proving that the original D-galacto configuration was
retained in each chain elongation step. Evidently, having
established the structure of 32, it can be safely assumed
that the sugar moieties in the lower oligomers 29-31
have an identical configuration. These results demon-
strate that the Wittig reactions in all four consecutive
cycles did not affect the configuration of the anomeric
carbon atom of the building block 7 nor that of the
stereocenters in the various phosphorus ylide intermedi-
ates. In closing this section, a comparison of routes A and
B appears worthwhile. Route A is plagued by substantial
side product formation in the coupling step, which makes
the approach unpractical after a few iterative cycles. On
the other hand, route B is characterized by high yields
in both the coupling and arming steps throughout four
consecutive cycles. This indicates that we did not reach
the limit of application of the method, and therefore,
oligomers higher that 32 can be in principle prepared by
this route.
Exp er im en ta l Section
All moisture-sensitive reactions were performed under a
nitrogen atmosphere using oven-dried glassware. Solvents
were dried over standard drying agent19 and freshly distilled
prior to use. Commercially available powdered 4 Å molec-
ular sieves (5 µm average particle size) were used without
further activation. Reactions were monitored by TLC on silica
gel 60 F254 with detection by charring with sulfuric acid. Flash
column chromatography20 was performed on silica gel 60
(230-400 mesh). Melting points were determined with a
capillary apparatus. Optical rotations were measured out at
20 ( 2 °C in the stated solvent; [R]D values are given in
10-1 deg cm2 g-1 1H (300 and 500 MHz), 13C (75 MHz), and
.
31P (121 MHz) NMR spectra were recorded for CDCl3 solu-
tions at room temperature unless otherwise specified. Assign-
ments were aided by homo- and heteronuclear two-dimen-
sional experiments. MALDI-TOF mass spectra were acquired
using R-cyano-4-hydroxycinnamic acid as the matrix. Sugar
lactones 121 and 3322 were prepared by oxidation of the
corresponding hemiacetal with pyridinium chlorochromate.23
Aldehyde 924 and iodides 1825 and 1926 were synthesized as
described.
To further prove the scope of route B, attention could
now be focused on the synthesis of â-C-(1,6)-linked
oligoglucoses, i.e., the isosteres of the â-(1,6)-glucooli-
gosaccharides known as gentiooligosaccharides which are
found in lichen.18 The required phosphonium iodide 21
was prepared as shown in Scheme 4 starting from the
iodoglucose 19, while the formyl C-glucoside building
block 36 having orthogonal protective groups was ob-
(19) Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory
Chemicals, 4th ed.; Butterworth-Heinemann: Oxford, 1996.
(20) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923-
2925.
(21) Dondoni, A.; Scherrmann, M.-C. J . Org. Chem. 1994, 59, 6404-
6412.
(18) Corradi da Silva, M. L.; Iacomini, M.; J ablonski, E.; Gorin, P.
A. J . Phytochemistry 1993, 33, 547-552.
(22) Kuzuhara, H.; Fletcher, H. J . Org. Chem. 1967, 32, 2531-2534.
(23) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 2647-2650.

Synthesis of Oligoglucoses and Oligogalactoses
J . Org. Chem., Vol. 67, No. 12, 2002 4191
Sch em e 5
2,3,4,6-Tet r a -O-b en zyl-1-C-(2-b en zot h ia zolyl)-r-D-ga -
la ctop yr a n ose (3). To a cooled (-65 °C), stirred solution of
n-BuLi (4.2 mL, 6.72 mmol, of a 1.6 M solution in hexane) in
anhydrous Et2O (15 mL) was added dropwise a solution of
freshly distilled 2-benzothiazole (0.91 g, 6.72 mmol) in anhy-
drous Et2O (8 mL) over a 30 min period. The yellow solution
was stirred at -65 °C for 30 min, and then a solution of
galactonolactone 1 (2.62 g, 4.86 mmol) in anhydrous Et2O (20
mL) was added slowly (20 min). After an additional 1 h at -65
°C the mixture was allowed to warm to -50 °C in 30 min and
then poured into 100 mL of a 1 M phosphate buffer at pH 7.
The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (2 × 100 mL). The combined organic
layers were dried (Na2SO4) and concentrated. The residue was
eluted from a column of silica gel with cyclohexane-AcOEt
5.06 and 4.72 (2 d, 2 H, J ) 11.3 Hz, PhCH2), 4.82 and 4.78 (2
d, 2 H, J ) 11.5 Hz, PhCH2), 4.78 and 4.42 (2 d, 2 H, J ) 11.0
Hz, PhCH2), 4.52 (d, 1 H, J 2,3 ) 9.7 Hz, H-2), 4.51 and 4.46 (2
d, 2 H, J ) 12.0 Hz, PhCH2), 4.37 (ddd, 1 H, J 4,5 ) 1.0, J 5,6a
)
8.0, J 5,6b ) 5.5 Hz, H-5), 4.15 (dd, 1 H, J 3,4 ) 2.8 Hz, H-4),
4.10 (dd, 1 H, H-3), 3.73 (dd, 1 H, H-6a), 3.63 (dd, 1 H, H-6b).
Anal. Calcd for C41H39NO6S (673.83): C, 73.08; H, 5.83; N,
2.08. Found: C, 73.26; H, 5.91; N, 2.00.
1-O-Acetyl-2,3,4,6-tetr a-O-ben zyl-1-C-(2-ben zoth iazolyl)-
r-D-ga la ctop yr a n ose (4). To a solution of 3 (4.72 g, 7.00
mmol) in anhydrous CH2Cl2 (50 mL) were added at rt distilled
triethylamine (10 mL) and acetic anhydride (10 mL). The
solution was kept at rt for 24 h and then concentrated to give
syrupy 4 (5.01 g, ca. 100%) at least 95% pure by 1H NMR
analysis. An analytical sample was obtained by column chro-
(from 15:1 to 9:1) to give 3 (2.45 g, 75%) as a syrup. [R]D
)
matography on silica gel (4:1 cyclohexane-AcOEt). [R]D
)
-15.8 (c 1.6, CHCl3). 1H NMR (300 MHz): δ 8.13-8.05 and
7.91-7.85 (2 m, 2 H, BTh), 7.60-6.97 (m, 22 H, 4 Ph, BTh),
+20.4 (c 1.4, CHCl3). 1H NMR (300 MHz): δ 8.11-8.03 and
7.88-7.80 (2 m, 2 H, BTh), 7.51-6.91 (m, 22 H, 4 Ph, BTh),
5.05 and 4.68 (2 d, 2 H, J ) 11.5 Hz, PhCH2), 4.85 and 4.80 (2
d, 2 H, J ) 12.0 Hz, PhCH2), 4.59 and 4.40 (2 d, 2 H, J ) 11.0
Hz, PhCH2), 4.56 and 4.48 (2 d, 2 H, J ) 11.5 Hz, PhCH2),
4.19-4.14 (m, 3 H, H-2, H-3, H-4), 4.04 (ddd, 1 H, J 4,5 ) 0.8,
J 5,6a ) 8.0, J 5,6b ) 5.3 Hz, H-5), 3.85 (dd, 1 H, J 6a,6b ) 9.0 Hz,
(24) Tronchet, J . M. J .; Massoud, M. A. M. Helv. Chim. Acta 1979,
62, 1632-1639.
(25) Desire, J .; Prandi, J . Eur. J . Org. Chem. 2000, 3075-3084.
(26) Kleban, M.; Kautz, U.; Greul, J .; Hilgers, P.; Kugler, R.; Dong,
H.-Q.; J aeger, V. Synthesis 2000, 1027-1033.

4192 J . Org. Chem., Vol. 67, No. 12, 2002
Dondoni et al.
2-(2,3,4-tr i-O-ben zyl-6-O-ter t-bu tyld ip h en ylsilyl-â-D-ga -
la ctop yr a n osyl)ben zoth ia zole (6). To a solution of 5 (5.26
g, 8.00 mmol) in acetic anhydride (60 mL) was added a solution
of 96% H2SO4 (0.8 mL) in acetic acid (28 mL). The reaction
mixture was kept at rt for 1.5 h, then diluted with AcOEt (300
mL), washed with H2O (3 × 100 mL) and saturated aqueous
Na2CO3 (2 × 100 mL), dried (Na2SO4), and concentrated. The
crude 6-O-acetylated derivative was treated with a freshly
prepared ∼0.1 M solution of CH3ONa in CH3OH (50 mL) at rt
for 3 h, then neutralized with acetic acid, and concentrated.
The residue was eluted from a column of silica gel with 3:1
cyclohexane-AcOEt to give 2-(2,3,4-tri-O-benzyl-â-D-galacto-
pyranosyl)benzothiazole (3.59 g) as a syrup. [R]D ) -31.6 (c
Ch a r t 3
1
1.5, CHCl3). H NMR (300 MHz): δ 8.12-8.06 and 7.94-7.87
(2 m, 2 H, BTh), 7.58-7.00 (m, 22 H, 4 Ph, BTh), 5.07 and
4.75 (2 d, 2 H, J ) 11.8 Hz, PhCH2), 4.85 (s, 2 H, PhCH2),
4.76 (d, 1 H, J 1,2 ) 9.5 Hz, H-1), 4.72 and 4.41 (2 d, 2 H, J )
10.7 Hz, PhCH2), 4.30 (dd, 1 H, J 2,3 ) 9.5 Hz, H-2), 3.98 (dd,
1 H, J 3,4 ) 2.8, J 4,5 ) 0.6 Hz, H-4), 3.89 (ddd, 1 H, J 5,6a ) 6.6,
J 6a,6b ) 11.0, J 6a,OH ) 3.4 Hz, H-6a), 3.81 (dd, 1 H, H-3), 3.67
(ddd, 1 H, J 5,6b ) 4.9 Hz, H-5), 3.58 (ddd, 1 H, J 6b,OH ) 8.4 Hz,
H-6b), 1.80 (dd, 1 H, OH). Anal. Calcd for
C34H33NO5S
(567.71): C, 71.93; H, 5.86; N, 2.47. Found: C, 71.72; H, 5.92;
N, 2.38. To a stirred solution of this alcohol in pyridine (60
mL) was added tert-butylchlorodiphenylsilane (2.46 mL,
9.48 mmol). Stirring was continued for an additional 16 h, and
then the reaction mixture was diluted with CH3OH (2 mL)
and concentrated. The residue was eluted from a column of
silica gel with 10:1 cyclohexane-AcOEt (containing 0.3%
triethylamine) to give 6 (4.90 g, 76% from 5) as a syrup. [R]D
) -15.6 (c 1.0, CHCl3). 1H NMR (300 MHz): δ 8.12-8.04 and
7.90-7.82 (2 m, 2 H, BTh), 7.68-7.00 (m, 27 H, 5 Ph, BTh),
5.10 and 4.73 (2 d, 2 H, J ) 11.8 Hz, PhCH2), 4.88 and 4.82 (2
d, 2 H, J ) 12.0 Hz, PhCH2), 4.70 (d, 1 H, J 1,2 ) 9.5 Hz, H-1),
4.68 and 4.38 (2 d, 2 H, J ) 11.0 Hz, PhCH2), 4.22 (dd, 1 H,
J 2,3 ) 9.5 Hz, H-2), 4.14 (dd, 1 H, J 3,4 ) 2.8, J 4,5 ) 0.7 Hz,
H-4), 3.92 (dd, 1 H, J 5,6a ) 8.0, J 6a,6b ) 10.0 Hz, H-6a), 3.83
(dd, 1 H, J 5,6b ) 5.5 Hz, H-6b), 3.78 (dd, 1 H, H-3), 3.65 (ddd,
1 H, H-5), 1.07 (s, 9 H, t-Bu). Anal. Calcd for C50H51NO5SSi
(806.11): C, 74.50; H, 6.38; N, 1.74. Found: C, 74.72; H, 6.44;
N, 1.68.
Sch em e 6a
2,6-An h yd r o-3,4,5-tr i-O-ben zyl-7-O-ter t-bu tyld ip h en yl-
silyl-a ld eh yd o-D-glycer o-L-m a n n o-h ep tose (7). A mixture
of 6 (1.46 g, 1.81 mmol), activated 4 Å powdered molecular
sieves (2.71 g), and anhydrous CH3CN (18 mL) was stirred at
rt for 10 min, and then methyl triflate (307 µL, 2.71 mmol)
was added. The suspension was stirred at rt for 20 min and
then concentrated to dryness without filtering off the molecular
sieves. To a cooled (0 °C), stirred suspension of the crude
N-methylbenzothiazolium salt in CH3OH (18 mL) was added
NaBH4 (103 mg, 2.71 mmol). The mixture was stirred at rt
for an additional 10 min, diluted with acetone, filtered through
a pad of Celite, and concentrated. To a vigorously stirred
solution of the diastereomeric benzothiazolines in CH2Cl2 (3
mL) and CH3CN (15 mL) were added H2O (1.8 mL) and then
AgNO3 (0.92 g, 5.43 mmol). The mixture was stirred at rt for
15 min, and then diluted with 1 M phosphate buffer at pH 7
(1.8 mL). Stirring was continued for an additional 15 min, and
then the reaction mixture was diluted with 1 M phosphate
buffer at pH 7 (50 mL) and partially concentrated to remove
CH3CN (bath temperature not exceeding 40 °C). The suspen-
sion was extracted with Et2O (2 × 100 mL), and the combined
organic phases were dried (Na2SO4), filtered through a pad of
Celite, and concentrated. The residue was eluted from a short
column (3 × 10 cm, diameter × height) of silica gel with 5:1
cyclohexane-AcOEt to afford syrupy 7 (1.03 g, 81%) ca. 95%
a
BTh ) 2-benzothiazolyl.
H-6a), 3.70 (dd, 1 H, H-6b), 2.22 (s, 3 H, Ac). Anal. Calcd for
43H41NO7S (715.87): C, 72.15; H, 5.77; N, 1.96. Found: C,
72.33; H, 5.86; N, 1.91.
C
2-(2,3,4,6-tetr a-O-ben zyl-â-D-galactopyr an osyl)ben zoth i-
a zole (5). To a stirred mixture of 4 (4.29 g, 6.00 mmol),
activated 4 Å powdered molecular sieves (6.0 g), and trieth-
ylsilane (9.6 mL, 60.0 mmol) in anhydrous CH2Cl2 (50 mL)
was added TMSOTf (1.63 mL, 9.00 mmol). The mixture was
stirred at rt for 1.5 h and then diluted with triethylamine (2
mL), filtered through Celite, and concentrated. The residue
was eluted from a column of silica gel with 5:1 cyclohexane-
AcOEt to give 5 (3.74 g, 95%) as a syrup. [R]D ) -20.5 (c 1.5,
CHCl3). 1H NMR (300 MHz): δ 8.11-8.04 and 7.92-7.86 (2
m, 2 H, BTh), 7.56-7.00 (m, 22 H, 4 Ph, BTh), 5.05 and 4.70
(2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.81 (s, 2 H, PhCH2), 4.76 (d,
1 H, J 1,2 ) 9.5 Hz, H-1), 4.70 and 4.40 (2 d, 2 H, J ) 10.8 Hz,
PhCH2), 4.52 and 4.45 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.26
1
pure by 1H NMR analysis. H NMR (300 MHz): δ 9.59 (d, 1
H, J 1,2 ) 1.2 Hz, H-1), 7.66-7.60 and 7.50-7.25 (2 m, 25 H, 5
Ph), 5.00 and 4.67 (2 d, 2 H, J ) 11.2 Hz, PhCH2), 4.90 and
4.69 (2 d, 2 H, J ) 10.6 Hz, PhCH2), 4.81 (s, 2 H, PhCH2),
4.07 (dd, 1 H, J 4,5 ) 2.6, J 5,6 ) 0.7 Hz, H-5), 4.06 (dd, 1 H, J 2,3
(dd, 1 H, J 2,3 ) 9.5 Hz, H-2), 4.09 (dd, 1 H, J 3,4 ) 2.8, J 4,5
)
0.6 Hz, H-4), 3.82 (dt, 1 H, J 5,6 ) 6.4 Hz, H-5), 3.80 (dd, 1 H,
H-3), 3.68 (d, 2 H, 2 H-6). Anal. Calcd for C41H39NO5S
(657.83): C, 74.86; H, 5.98; N, 2.13. Found: C, 74.78; H, 6.09;
N, 2.08.
) 10.0, J 3,4 ) 9.0 Hz, H-3), 3.88 (dd, 1 H, J 6,7a ) 8.2, J 7a,7b )
10.3 Hz, H-7a), 3.83 (dd, 1 H, J 6,7b ) 5.7 Hz, H-7b), 3.71 (dd,
1 H, H-2), 3.68 (dd, 1 H, H-4), 3.48 (ddd, 1 H, H-6), 1.08 (s, 9
H, t-Bu).

Synthesis of Oligoglucoses and Oligogalactoses
J . Org. Chem., Vol. 67, No. 12, 2002 4193
Sch em e 7
(2,6-An h yd r o-3,4,5-tr i-O-ben zyl-7-O-ter t-bu tyld ip h en -
y ls ily l-1-d e o x y -D-g l ycer o-L-m a n n o-h e p t it o l-1-y l)t r i-
p h en ylp h osp h on iu m Iod id e (8). To a cooled (0 °C), stirred
solution of aldehyde 7 (3.14 g, 4.48 mmol) in Et2O (22 mL)
and CH3OH (22 mL) was added NaBH4 (170 mg, 4.48 mmol).
The mixture was stirred at rt for an additional 10 min, then
diluted with acetone (1 mL), and concentrated. The residue
was suspended in Et2O (200 mL), washed with H2O (2 × 50
mL), dried (Na2SO4), and concentrated to afford 2,6-anhydro-
3,4,5-tri-O-benzyl-7-O-tert-butyldiphenylsilyl-D-glycero-L-manno-
heptitol (3.12 g). 1H NMR (300 MHz): δ 7.75-7.72, 7.68-7.63,
and 7.46-7.25 (3 m, 25 H, 5 Ph), 4.99 and 4.64 (2 d, 2 H, J )
11.4 Hz, PhCH2), 4.93 and 4.66 (2 d, 2 H, J ) 11.0 Hz, PhCH2),
4.79 (s, 2 H, PhCH2), 4.03 (dd, 1 H, J 4,5 ) 2.7, J 5,6 ) 0.5 Hz,
H-5), 3.92 (dd, 1 H, J 2,3 ) J 3,4 ) 9.5 Hz, H-3), 3.81-3.73 and
3.68-3.61 (2 m, 2 H, 2 H-1), 3.76 (d, 2 H, J 6,7 ) 6.8 Hz, 2 H-7),
heptitol (3.18 g). 1H NMR (300 MHz): δ 7.75-7.60 and 7.44-
7.17 (2 m, 25 H, 5 Ph), 5.01 and 4.65 (2 d, 2 H, J ) 11.7 Hz,
PhCH2), 4.98 and 4.72 (2 d, 2 H, J ) 10.8 Hz, PhCH2), 4.78
and 4.73 (2 d, 2 H, J ) 11.9 Hz, PhCH2), 4.02 (dd, 1 H, J 4,5
)
2.6, J 5,6 ) 0.5 Hz, H-5), 3.81 (dd, 1 H, J 2,3 ) 8.9, J 3,4 ) 9.3 Hz,
H-3), 3.79 (d, 2 H, J 6,7 ) 6.8 Hz, 2 H-7), 3.62 (dd, 1 H, H-4),
3.46 (dt, 1 H, H-6), 3.45 (dd, 1 H, J 1a,2 ) 2.5, J 1a,1b ) 10.6 Hz,
H-1a), 3.30 (dd, 1 H, J 1b,2 ) 6.6 Hz, H-1b), 3.09 (ddd, 1 H, H-2),
1.06 (s, 9 H, t-Bu). A mixture of iodide (3.18 g, 3.91 mmol)
and triphenylphosphine (10.25 g, 39.10 mmol) was stirred at
120 °C under a nitrogen atmosphere for 2 h, then cooled to
ca. 80 °C, diluted with toluene (20 mL), cooled to rt, and diluted
with Et2O (40 mL). The white solid was filtered, washed with
Et2O, and dried to give 8 (3.13 g, 65% from 7). Mp 182-183
1
°C. [R]D ) -9.3 (c 0.8, CHCl3). H NMR (300 MHz): δ 7.83-
7.18 (m, 40 H, 8 Ph), 5.06 and 4.92 (2 d, 2 H, J ) 11.4 Hz,
PhCH2), 4.99 and 4.60 (2 d, 2 H, J ) 11.2 Hz, PhCH2), 4.78 (s,
2 H, PhCH2), 3.98 (dd, 1 H, J 4,5 ) 2.6, J 5,6 ) 0.6 Hz, H-5), 3.95
(dd, 1 H, J 2,3 ) J 3,4 ) 9.2 Hz, H-3), 3.60 (dd, 1 H, H-4), 3.56-
3.45 (m, 2 H, H-1a, H-2), 3.40 (dd, 1 H, J 6,7a ) 8.5, J 7a,7b ) 9.8
Hz, H-7a), 3.28-3.18 (m, 1 H, H-1b), 3.10 (dd, 1 H, J 6,7b ) 5.4
Hz, H-6), 2.91 (dd, 1 H, H-7b), 1.00 (s, 3 H, t-Bu). 31P NMR
(121 MHz): δ 23.7. Anal. Calcd for C62H64IO5PSi (1075.16):
C, 69.26; H, 6.00. Found: C, 68.98; H, 5.96.
3.62 (dd, 1 H, H-4), 3.46 (dt, 1 H, H-6), 3.30 (ddd, 1 H, J 1a,2
)
2.2, J 1b,2 ) 5.4 Hz, H-2), 1.06 (s, 9 H, t-Bu). To a vigorously
stirred solution of the crude alcohol, triphenylphosphine (1.76
g, 6.72 mmol), and imidazole (0.91 g, 13.44 mmol) in anhydrous
toluene (45 mL) was added iodine (1.71 g, 6.72 mmol). The
mixture was stirred at 80 °C for 2 h, then cooled to rt, filtered
through a pad of Celite, and concentrated. A solution of the
residue in Et2O (200 mL) was washed with 5% aqueous
Na2S2O3 (2 × 50 mL), dried (Na2SO4), and concentrated. The
residue was eluted from a column of silica gel with 4:1
cyclohexane-AcOEt to give 2,6-anhydro-3,4,5-tri-O-benzyl-7-
O-tert-butyldiphenylsilyl-1-deoxy-1-iodo-D-glycero-L-manno-
(E,Z)-8,12-An h yd r o-9,10,11-t r i-O-b en zyl-13-O-ter t-b u -
tyld ip h en ylsilyl-6,7-d id eoxy-1,2:3,4-d i-O-isop r op ylid en e-
r-D-glycer o-L-m a n n o-D-ga la ct o-t r id e c-6-e n o-1,5-p yr a -
n ose (10). To a cooled (-50 °C), stirred mixture of 8 (1.08 g,

4194 J . Org. Chem., Vol. 67, No. 12, 2002
Dondoni et al.
mmol). The reaction mixture was stirred at rt for 30 min, then
diluted with Et2O (24 mL) and cyclohexane (12 mL), stirred
for an additional 10 min, and eluted from a short column of
silica gel (4 × 3 cm, diameter × height) with 2:1 cyclohexane-
Et2O to give syrupy 11 (0.33 g, 70% from 10) ca. 95% pure by
1H NMR analysis. 1H NMR (300 MHz) selected data for the
Z-isomer: δ 9.60 (s, 1 H, H-13), 7.35-7.26 (m, 15 H, 3 Ph),
5.92 (dd, 1 H, J 5,6 ) 8.0, J 6,7 ) 11.3 Hz, H-6), 5.84 (dd, 1 H,
J 7,8 ) 8.0 Hz, H-7), 5.50 (d, 1 H, J 1,2 ) 5.1 Hz, H-1), 4.32 (dd,
1 H, J 2,3 ) 2.3, J 3,4 ) 7.9 Hz, H-3), 4.23 (dd, 1 H, H-2), 4.18
(dd, 1 H, J 8,9 ) 9.1 Hz, H-8), 3.82 (dd, 1 H, J 9,10 ) 9.3 Hz,
Ch a r t 4
H-9), 3.76 (d, 1 H, J 11,12 ) 1.2 Hz, H-12), 3.72 (dd, 1 H, J 4,5
)
1.7 Hz, H-4), 3.59 (dd, 1 H, J 10,11 ) 2.7 Hz, H-10), 1.44, 1.42,
1.30, and 1.18 (4 s, 12 H, 4 CH3). MALDI-TOF MS (686.81):
m/z 710.0 (M + Na), 725.9 (M + K).
Tr isa cch a r id e 12. Aldehyde 11 (137 mg, 0.20 mmol) was
treated with 8 (237 mg, 0.22 mmol) as described for the
preparation of 10. The crude product was eluted from a column
of silica gel with 4:1 cyclohexane-AcOEt (containing 0.3%
triethylamine) to give first 12a (45 mg, 18%) as a syrup. 1H
NMR (300 MHz) selected data: δ 5.92 (dd, 1 H, J 5,6 ) 8.8, J 6,7
) 11.5 Hz, H-6), 5.86 (d, 1 H, J 13,14 ) 11.7 Hz, H-13), 5.70 (dd,
1 H, J 7,8 ) 8.3 Hz, H-7), 5.50 (dd, 1 H, J 14,15 ) 8.9 Hz, H-14),
5.50 (d, 1 H, J 1,2 ) 4.5 Hz, H-1), 5.10 (dd, 1 H, J 10,11 ) 2.1 Hz,
H-11). MALDI-TOF MS (1247.6): m/z 1270.9 (M + Na), 1287.0
(M + K). Eluted second was syrupy 12 (98 mg, 36%) as a ca.
9:1 E,Z-mixture. 1H NMR (300 MHz) selected data for the
6Z,13E-isomer: δ 7.66-7.61, 7.44-7.23, and 7.14-6.98 (3 m,
40 H, 8 Ph), 5.86 (dd, 1 H, J 12,13 ) 7.0, J 13,14 ) 16.0 Hz, H-13),
5.82-5.75 (m, 2 H, H-6, H-7), 5.71 (dd, 1 H, J 14,15 ) 3.6 Hz,
1.00 mmol) and activated 4 Å powdered molecular sieves (1.0
g) in anhydrous THF (4 mL) and HMPA (2 mL) were added
n-BuLi (625 µL, 1.00 mmol, of a 1.6 M solution in hexane) and,
after 5 min, a solution of 9 (387 mg, 1.50 mmol) in anhydrous
THF (2 mL). The mixture was allowed to reach -20 °C in 3 h,
then diluted with Et2O (150 mL), filtered through a pad of
Celite, washed with 1 M phosphate buffer at pH 7 (30 mL),
dried (Na2SO4), and concentrated. The residue was eluted from
a column of silica gel with 6:1 cyclohexane-AcOEt (containing
0.5% triethylamine) to give syrupy 10 (0.65 g, 70%) as a ca.
9:1 Z,E mixture. 1H NMR (300 MHz) of the Z-isomer: δ 7.64-
7.54 and 7.46-7.24 (2 m, 25 H, 5 Ph), 5.77 (dd, 1 H, J 5,6 ) 8.0,
J 6,7 ) 11.2 Hz, H-6), 5.66 (dd, 1 H, J 7,8 ) 8.0 Hz, H-7), 5.48 (d,
1 H, J 1,2 ) 5.0 Hz, H-1), 4.99 and 4.65 (2 d, 2 H, J ) 11.2 Hz,
PhCH2), 4.91 and 4.62 (2 d, 2 H, J ) 11.2 Hz, PhCH2), 4.76 (s,
2 H, PhCH2), 4.63 (dd, 1 H, J 4,5 ) 2.6 Hz, H-5), 4.27 (dd, 1 H,
J 2,3 ) 2.2, J 3,4 ) 8.0 Hz, H-3), 4.22 (dd, 1 H, H-2), 4.11 (d, 1 H,
J 10,11 ) 3.0 Hz, H-11), 4.01 (dd, 1 H, J 8,9 ) 9.4 Hz, H-8), 3.84
(dd, 1 H, J 9,10 ) 9.4 Hz, H-9), 3.78-3.71 (m, 3 H, H-10, 2 H-13),
3.58 (dd, 1 H, H-4), 3.42 (dd, 1 H, J 12,13a ) 5.0, J 12,13b ) 8.5 Hz,
H-12), 1.48, 1.44, 1.42, and 1.33 (4 s, 12 H, 4 CH3), 1.08 (s, 9
H, t-Bu). Anal. Calcd for C56H66O10Si (927.23): C, 72.54; H,
7.17. Found: C, 72.41; H, 7.25.
(E,Z)-8,12-An h yd r o-9,10,11-t r i-O-b en zyl-6,7-d id eoxy-
1,2:3,4-di-O-isopr opyliden e-r-D-glycer o-L-ma n n o-D-ga la cto-
tr id ec-6-en o-1,5-p yr a n od ia ld ose (11). A solution of 10 (0.63
g, 0.68 mmol) and n-Bu4NF.3H2O (0.32 g, 1.02 mmol) in
distilled THF (14 mL) was kept at rt for 3 h, then diluted with
1 M phosphate buffer at pH 7 (20 mL), and extracted with
Et2O (2 × 100 mL). The combined organic layers were dried
(Na2SO4) and concentrated. The residue was eluted from a
column of silica gel with 2:1 cyclohexane-AcOEt to give (E,Z)-
8,12-anhydro-9,10,11-tri-O-benzyl-6,7-dideoxy-1,2:3,4-di-O-iso-
propylidene-R-D-glycero-L-manno-D-galacto-tridec-6-eno-1,5-
pyranose (0.42 g) as a syrup. 1H NMR (300 MHz) selected data
for the Z-isomer: δ 7.38-7.26 (m, 15 H, 3 Ph), 5.84 (dd, 1 H,
J 5,6 ) 8.0, J 6,7 ) 11.4 Hz, H-6), 5.76 (dd, 1 H, J 7,8 ) 7.6 Hz,
H-7), 5.51 (d, 1 H, J 1,2 ) 5.1 Hz, H-1), 4.97 and 4.68 (2 d, 2 H,
J ) 11.8 Hz, PhCH2), 4.93 and 4.66 (2 d, 2 H, J ) 11.2 Hz,
PhCH2), 4.78 and 4.74 (2 d, 2 H, J ) 11.8 Hz, PhCH2), 4.33
(dd, 1 H, J 2,3 ) 2.4, J 3,4 ) 7.9 Hz, H-3), 4.24 (dd, 1 H, H-2),
4.07 (dd, 1 H, J 8,9 ) 9.3 Hz, H-8), 3.59 (dd, 1 H, J 9,10 ) 9.3,
J 10,11 ) 2.8 Hz, H-10), 1.54, 1.44, 1.33, and 1.17 (4 s, 12 H, 4
CH3). To a vigorously stirred mixture of this alcohol, activated
4 Å powdered molecular sieves (1.2 g), and anhydrous CH2Cl2
(12 mL) was added pyridinium chlorochromate (0.40 g, 1.83
H-14), 5.46 (d, 1 H, J 1,2 ) 4.8 Hz, H-1), 4.05 (dd, 1 H, J 7,8
7.1, J 8,9 ) 9.4 Hz, H-8), 3.53 (dd, 1 H, J 9,10 ) 9.7, J 10,11 ) 2.9
Hz, H-10), 3.43 (ddd, 1 H, J 18,19 ) 0.6, J 19,20a ) 5.1, J 19,20b
)
)
8.6 Hz, H-19), 1.51, 1.41, 1.30, and 1.28 (4 s, 12 H, 4 CH3),
1.07 (s, 9 H, t-Bu). MALDI-TOF MS (1355.76): m/z 1379.4 (M
+ Na), 1395.4 (M + K). Anal. Calcd for C84H94O14Si: C, 74.42;
H, 6.99. Found: C, 74.23; H, 7.15.
Tr isa cch a r id e 13. Trisaccharide 12 (203 mg, 0.15 mmol)
was desilylated and oxidized as described for the preparation
of 11 to give syrupy 13 (119 mg, 71%) ca. 95% pure by 1H NMR
analysis. 1H NMR (300 MHz) selected data for the 13E-
isomer: δ 9.59 (s, 1 H, H-20), 7.49-7.13 (m, 30 H, 5 Ph), 6.00
(dd, 1 H, J 12,13 ) 7.0, J 13,14 ) 16.0 Hz, H-13), 5.48 (d, 1 H, J 1,2
) 5.0 Hz, H-1), 1.45, 1.41, 1.32, and 1.09 (4 s, 12 H, 4 CH3).
MALDI-TOF MS (1115.34): m/z 1138.5 (M + Na), 1154.8 (M
+ K).
Tetr a sa cch a r id e 14. Aldehyde 13 (112 mg, 0.10 mmol) was
treated with 8 (161 mg, 0.15 mmol) as described for the
preparation of 10. The crude product was eluted from a column
of silica gel with 4:1 cyclohexane-AcOEt (containing 0.3%
triethylamine) to give first 14a (47 mg, 28%) as a syrup. 1H
NMR (300 MHz) selected data: δ 6.00 (dd, 1 H, J ) 6.3, 16.0
Hz), 5.76 (dd, 1 H, J ) 7.8, 11.0 Hz), 5.56 (dd, 1 H, J ) 8.8,
12.0 Hz), 5.44 (d, 1 H, J 1,2 ) 4.9 Hz, H-1), 5.17 (d, 1 H, J 17,18
) 2.7 Hz, H-18). MALDI-TOF MS (1676.15): m/z 1699.2 (M
+ Na), 1715.6 (M + K). Eluted second was 14 (20 mg, 11%)
slightly contaminated by 14a . An analytical sample was
obtained by preparative thin-layer chromatography on silica
gel (6:3:1 pentane-CH2Cl2-Et2O). 1H NMR (300 MHz) selected
data: δ 7.66-7.61, 7.53-7.11, and 7.05-6.99 (3 m, 55 H, 11
Ph), 5.47 (d, 1 H, J 1,2 ) 4.6 Hz, H-1), 1.56, 1.41, 1.34, and 1.27
(4 s, 12 H, 4 CH3), 1.07 (s, 9 H, t-Bu). MALDI-TOF MS
(1784.29): 1808.0 (M + Na), 1824.0 (M + K). Anal. Calcd. for
C
112H122O18Si: C, 75.39; H, 6.89. Found: C, 75.56; H, 7.01.
9,10,11,13-Tetr a -O-a cetyl-8,12-a n h yd r o-6,7-d id eoxy-1,2:
3,4-d i-O-isop r op ylid en e-r-D-glycer o-L-m a n n o-D-ga la cto-
tr id eco-1,5-p yr a n ose (15Ac). Disaccharide 10 (139 mg, 0.15
mmol) was desilylated as described for the preparation of 11.
A vigorously stirred mixture of the resulting alcohol, 20%
palladium hydroxide on carbon (60 mg), and 1:1 CH3OH-
AcOEt (10 mL) was degassed under a vacuum and saturated
with hydrogen (by a H2-filled balloon) three times. The
suspension was stirred at rt for 6 h under a positive pressure
of hydrogen (4 bar), then filtered through a plug of cotton, and
concentrated. A solution of crude 15 in pyridine (2 mL) and

Synthesis of Oligoglucoses and Oligogalactoses
J . Org. Chem., Vol. 67, No. 12, 2002 4195
acetic anhydride (2 mL) was kept at rt for 4 h, and then
concentrated. The residue was eluted from a column of silica
gel with 2:1 cyclohexane-AcOEt to give 15Ac (62 mg, 70%)
2.05, 2.04, 1.98, and 1.97 (8 s, 30 H, 10 Ac), 1.87-1.79 (m, 2
H, 2 H-6), 1.73-1.60 (m, 6 H, 2 H-7, 2 H-14, 2 H-21), 1.52-
1.43 (m, 4 H, 2 H-13, 2 H-20), 1.51, 1.48, 1.35, and 1.33 (4 s,
12 H, 4 CH3). MALDI-TOF MS (1161.19): m/z 1184.8 (M +
Na), 1201.3 (M + K). Anal. Calcd for C53H76O28: C, 54.82; H,
6.60. Found: C, 55.01; H, 6.65.
1
as a syrup. [R]D ) -32.1 (c 1.9, CHCl3). H NMR (300 MHz):
δ 5.51 (d, 1 H, J 1,2 ) 5.1 Hz, H-1), 5.41 (dd, 1 H, J 10,11 ) 3.3,
J 11,12 ) 1.1 Hz, H-11), 5.09 (dd, 1 H, J 8,9 ) 9.7, J 9,10 ) 10.0 Hz,
H-9), 4.99 (dd, 1 H, H-10), 4.58 (dd, 1 H, J 2,3 ) 2.3, J 3,4 ) 6.9
Hz, H-3), 4.29 (dd, 1 H, H-2), 4.14 (dd, 1 H, J 12,13a ) 6.6, J 13a,13b
) 11.5 Hz, H-13a), 4.12 (dd, 1 H, J 4,5 ) 1.8 Hz, H-4), 4.07 (dd,
1 H, J 12,13b ) 6.8, H-13b), 3.84 (dd, 1 H, H-12), 3.69 (ddd, 1 H,
(Meth yl 2,3,4-tr i-O-ben zyl-6-d eoxy-D-ga la ctop yr a n o-
sid -6-yl)tr ip h en ylp h osp h on iu m Iod id e (20). A mixture of
iodide 18 (2.64 g, 4.60 mmol) and triphenylphosphine (12.05
g, 46.00 mmol) was stirred at 120 °C under a nitrogen
atmosphere for 4 h, and then cooled to room temperature. A
solution of the residue in CH2Cl2 (20 mL) was added dropwise
to a stirred volume of Et2O (ca. 1.2 L), and the white solid
was filtered, washed with Et2O, and dried to give 20 (3.42 g,
89%). Mp 93-94 °C. [R]D ) +50.5 (c 0.7, CHCl3). 1H NMR (300
MHz): δ 7.81-7.23 (m, 30 H, 6 Ph), 5.14 and 4.89 (2 d, 2 H,
J ) 11.2 Hz, PhCH2), 5.09 (ddd, 1 H, J 5,6a ) 3.0, J 6a,6b ) J 6a,P
) 16.0 Hz, H-6a), 4.96 (ddd, 1 H, J 3,4 ) 2.6, J 4,5 ) J 4,P ) 1.0
Hz, H-4), 4.92 and 4.82 (2 d, 2 H, J ) 11.5 Hz, PhCH2), 4.85
and 4.67 (2 d, 2 H, J ) 12.3 Hz, PhCH2), 4.45 (dddd, 1 H, J 5,6b
) 10.7, J 5,P ) 10.0 Hz, H-5), 4.39 (d, 1 H, J 1,2 ) 3.6 Hz, H-1),
4.07 (dd, 1 H, J 2,3 ) 10.3 Hz, H-3), 3.98 (dd, 1 H, H-2), 3.50
(ddd, 1 H, J 6b,P ) 10.3 Hz, H-6b), 2.48 (s, 3 H, CH3). 31P NMR
(121 MHz): δ 24.9. Anal. Calcd for C46H46IO5P (836.75): C,
66.03, H, 5.54. Found: C, 66.21, H, 5.59.
J 4,5 ) J 5,6a ) 2.0, J 5,6b ) 8.4 Hz, H-5), 3.44 (ddd, 1 H, J 7a,8
)
2.0, J 7b,8 ) 9.5 Hz, H-8), 2.17, 2.06, 2.05, and 1.99 (4 s, 12 H,
4 Ac), 1.88-1.76, 1.77-1.65, and 1.50-1.44 (3 m, 4 H, 2 H-6,
2 H-7), 1.52, 1.48, 1.36, and 1.34 (4 s, 12 H, 4 CH3). Anal. Calcd
for C27H40O14 (588.62): C, 55.09; H, 6.85. Found: C, 54.94; H
6.97.
P er a cetyla ted Tr isa cch a r id e 16Ac. Trisaccharide 12 (68
mg, 0.05 mmol) was desilylated as described for the prepara-
tion of 13. A vigorously stirred mixture of the resulting alcohol,
20% palladium hydroxide on carbon (30 mg), and 1:1 CH3OH-
AcOEt (5 mL) was degassed under a vacuum and saturated
with hydrogen (by a H2-filled balloon) three times. The
suspension was stirred at rt for 9 h under a positive pressure
of hydrogen (4 bar), then filtered through a plug of cotton, and
concentrated to give 16. 1H NMR (CD3OD, 300 MHz) selected
data: δ 5.44 (d, 1 H, J 1,2 ) 4.9 Hz, H-1), 4.59 (dd, 1 H, J 2,3
)
(Meth yl 2,3,4-tr i-O-ben zyl-6-d eoxy-D-glu cop yr a n osid -
6-yl)tr ip h en ylp h osp h on iu m Iod id e (21). Iodide 19 (5.00 g,
8.70 mmol) was treated with triphenylphosphine (22.82 g,
87.00 mmol) as described for the preparation of 20 to give 21
(6.34 g, 87%) identical in all respects to the product that we
prepared using different reaction conditions.5a
2.2, J 3,4 ) 7.8 Hz, H-3), 4.30 (dd, 1 H, H-2), 4.16 (dd, 1 H, J 4,5
) 0.8 Hz, H-4), 1.48, 1.38, 1.33, and 1.32 (4 s, 12 H, 4 CH3). A
solution of crude 16 in pyridine (2 mL) and acetic anhydride
(2 mL) was kept at rt for 8 h, and then concentrated. The
residue was eluted from a column of silica gel with 1.5:1
cyclohexane-AcOEt to give 16Ac (26 mg, 59%) as a syrup.
Meth yl 8,12-An h yd r o-2,3,4,9,10,11-h exa -O-ben zyl-13-O-
ter t-bu tyld ip h en ylsilyl-6,7-d id eoxy-r-D-glycer o-L-m a n n o-
D-ga la cto-tr id ec-6-(Z)-en o-1,5-p yr a n osid e (22). To a cooled
(-20 °C), stirred mixture of aldehyde 7 (1.05 g, 1.50 mmol),
iodide 20 (0.84 g, 1.00 mmol), activated 4 Å powdered molec-
ular sieves (1.5 g), anhydrous THF (12 mL), and anhydrous
HMPA (4 mL) was added n-BuLi (0.62 mL, 1.00 mmol, of a
1.6 M solution in hexane) by a syringe-pump apparatus over
4 h. After that period the reaction mixture was diluted with
Et2O (150 mL), filtered through a pad of Celite, washed with
1 M phosphate buffer (30 mL), dried (Na2SO4), and concen-
trated. The residue was eluted from a column of silica gel with
15:1 cyclohexane-AcOEt to give 22 (1.28 g, 81%) as a syrup.
1
[R]D ) -20.2 (c 0.6, CHCl3). H NMR (300 MHz): δ 5.51 (d, 1
H, J 1,2 ) 5.1 Hz, H-1), 5.40 (dd, 1 H, J 17,18 ) 3.2, J 18,19 ) 1.0
Hz, H-18), 5.29 (dd, 1 H, J 10,11 ) 3.2, J 11,12 ) 0.7 Hz, H-11),
5.08 (dd, 1 H, J 8,9 ) 9.8, J 9,10 ) 10.0 Hz, H-9), 5.07 (dd, 1 H,
J 15,16 ) 9.8, J 16,17 ) 10.0 Hz, H-16), 4.98 (dd, 1 H, H-17), 4.97
(dd, 1 H, H-10), 4.58 (dd, 1 H, J 2,3 ) 2.2, J 3,4 ) 7.1 Hz, H-3),
4.28 (dd, 1 H, J 2,3 ) 2.2 Hz, H-2), 4.18-4.03 (m, 3 H, H-4, 2
H-20), 3.85 (dd, 1 H, J 19,20a ) 5.8, J 19,20b ) 6.8 Hz, H-19), 3.70-
3.66 (m, 1 H, H-5), 3.52-3.48 (m, 1 H, H-12), 3.43-3.32 (m, 2
H, H-8, H-15), 2.18, 2.16, 2.05, 2.04, and 1.97 (5 s, 21 H, 7
Ac), 1.86-1.78 (m, 2 H, 2 H-6), 1.72-1.60 (m, 4 H, 2 H-7, 2
H-14), 1.47-1.42 (m, 2 H, 2 H-13), 1.50, 1.46, 1.35, 1.32 (4 s,
12 H, 4 CH3). 13C NMR (75.1 MHz): δ 20.7, 20.8, 24.3, 25.0,
26.1, 16.0, 26.4, 27.2, 28.4, 61.7, 67.7, 68.6, 69.7, 69.7, 70.5,
70.9, 72.2, 72.9, 73.0, 74.0, 76.9, 77.2, 77.7, 78.3, 96.5, 108.3,
109.1, 169.8, 169.9, 170.2, 170.3, 170.5, 170.7. MALDI-TOF
MS (874.90): m/z 898.2 (M + Na), 914.6 (M + K). Anal. Calcd
for C40H58O21: C, 54.91; H, 6.68. Found: C, 55.20; H, 6.52.
P er a cetyla ted Tetr a sa cch a r id e 17Ac. Tetrasaccharide
14 (89 mg, 0.05 mmol) was desilylated as described for the
preparation of 13. A vigorously stirred mixture of the resulting
alcohol, 20% palladium hydroxide on carbon (30 mg), and 1:1
CH3OH-AcOEt (5 mL) was degassed under a vacuum and
saturated with hydrogen (by a H2-filled balloon) three times.
The suspension was stirred at rt for 9 h under a positive
pressure of hydrogen (4 bar), then filtered through a plug of
cotton, and concentrated to give 17. 1H NMR (CD3OD, 300
MHz) selected data: δ 5.48 (d, 1 H, J 1,2 ) 5.1 Hz, H-1), 4.59
(dd, 1 H, J 2,3 ) 2.2, J 3,4 ) 8.0 Hz, H-3), 4.31 (dd, 1 H, H-2),
4.18 (dd, 1 H, J 4,5 ) 1.3 Hz, H-4), 1.49, 1.40, 1.32, and 1.29 (4
s, 12 H, 4 CH3). A solution of crude 17 in pyridine (2 mL) and
acetic anhydride (2 mL) was kept at rt for 16 h, and then
concentrated. The residue was eluted from a column of silica
gel with 1:2 cyclohexane-AcOEt to give 17Ac (35 mg, 61%)
1
[R]D ) +5.7 (c 1.5, CHCl3). H NMR (300 MHz) selected data:
δ 7.68-7.56 (m, 4 H, Ar), 7.48-7.15 (m, 36 H, Ar), 5.87 (dd, 1
H, J 5,6 ) 9.0, J 6,7 ) 11.2 Hz, H-6), 5.65 (dd, 1 H, J 7,8 ) 8.3 Hz,
H-7), 4.66 (d, 1 H, J 1,2 ) 3.5 Hz, H-1), 4.59 (dd, 1 H, J 4,5 ) 0.6
Hz, H-5), 4.10 (dd, 1 H, J 10,11 ) 2.9, J 11,12 ) 0.6 Hz, H-11),
3.99 (dd, 1 H, J 2,3 ) 10.0 Hz, H-2), 3.97 (dd, 1 H, J 8,9 ) 9.6 Hz,
H-8), 3.84 (dd, 1 H, J 12,13a ) 8.0, J 13a,13b ) 9.6 Hz, H-13a), 3.83
(dd, 1 H, J 3,4 ) 2.4 Hz, H-3), 3.76 (dd, 1 H, J 9,10 ) 9.3 Hz,
H-9), 3.72 (dd, 1 H, J 12,13b ) 5.6 Hz, H-13b), 3.64 (dd, 1 H,
H-10), 3.60 (dd, 1 H, H-4), 3.40 (ddd, 1 H, H-12), 3.27 (s, 3 H,
OCH3), 1.05 (s, 9 H, t-Bu). MALDI-TOF MS (1131.50): m/z
1154.8 (M + Na), 1170.6 (M + K). Anal. Calcd for C72H78O10
Si: C, 76.43; H, 6.95. Found: C, 76.30; H, 7.07.
-
When the reaction was performed using an excess of
phosphonium iodide 20 (1.2 equiv), the C-disaccharide 22 was
isolated in 61% yield.
(Meth yl 8,12-a n h yd r o-2,3,4,9,10,11-h exa -O-ben zyl-6,7,-
13-t r id eoxy-r-D-glycer o-L-m a n n o-D-ga la cto-t r id ec-6-(Z)-
en o-1,5-p yr a n osid -13-yl)t r ip h en ylp h osp h on iu m Iod id e
(23). A solution of 22 (1.13 g, 1.00 mmol) and n-Bu4NF.3H2O
(0.95 g, 3.00 mmol) in distilled THF (20 mL) was refluxed for
2 h, then cooled to rt, diluted with 1 M phosphate buffer at
pH 7 (40 mL), and extracted with Et2O (2 × 100 mL). The
combined organic layers were dried (Na2SO4) and concen-
trated. The residue was eluted from a column of silica gel with
cyclohexane-AcOEt (from 2:1 to 1:1) to give methyl 8,12-
anhydro-2,3,4,9,10,11-hexa-O-benzyl-6,7-dideoxy-R-D-glycero-
L-manno-D-galacto-tridec-6-(Z)-eno-1,5-pyranoside (0.86 g). 1H
NMR (300 MHz) selected data: δ 5.90 (dd, 1 H, J 5,6 ) 8.8, J 6,7
) 11.2 Hz, H-6), 5.73 (dd, 1 H, J 7,8 ) 8.0 Hz, H-7), 3.36 (s, 3
H, CH3). To a vigorously stirred solution of the alcohol,
1
as a syrup. [R]D ) -12.0 (c 0.2, CHCl3). H NMR (300 MHz)
selected data: δ 5.51 (d, 1 H, J 1,2 ) 4.9 Hz, H-1), 5.40 (dd, 1
H, J 24,25 ) 3.3, J 25,26 ) 0.6 Hz, H-25), 5.28 (dd, 1 H, J 17,18
3.2, J 18,19 ) 0.5 Hz, H-18), 5.28 (dd, 1 H, J 10,11 ) 3.2, J 11,12
)
)
0.5 Hz, H-11), 5.09 (dd, 1 H, J 22,23 ) J 23,24 ) 9.8 Hz, H-23),
5.07 (dd, 1 H, J 15,16 ) J 16,17 ) 9.8 Hz, H-16), 5.04 (dd, 1 H, J 8,9
) J 9,10 ) 9.8 Hz, H-9), 4.58 (dd, 1 H, J 2,3 ) 2.2, J 3,4 ) 7.8 Hz,
H-3), 4.29 (dd, 1 H, H-2), 3.84 (ddd, 1 H, J 26,27a ) 5.6, J 26,27b
7.3 Hz, H-26), 3.69-3.66 (m, 1 H, H-5), 2.19, 2.18, 2.16, 2.06,
)

4196 J . Org. Chem., Vol. 67, No. 12, 2002
Dondoni et al.
triphenylphosphine (0.50 g, 1.92 mmol), and imidazole (0.26
g, 3.83 mmol) in anhydrous toluene (20 mL) was added iodine
(0.49 g, 1.92 mmol). The mixture was refluxed for 1 h, then
cooled to rt, filtered through a pad of Celite, and concentrated.
A solution of the residue in CH2Cl2 (100 mL) was washed with
5% aqueous Na2S2O3 (2 × 30 mL), dried (Na2SO4), and
concentrated. Column chromatography of the residue (2:1
CH2Cl2-cyclohexane, and then 9:1 cyclohexane-AcOEt) gave
methyl 8,12-anhydro-2,3,4,9,10,11-hexa-O-benzyl-6,7,13-tri-
deoxy-13-iodo-R-D-glycero-L-manno-D-galacto-tridec-6-(Z)-eno-
slightly contaminated by triphenylphosphine. 1H NMR (300
MHz) selected data: δ 5.91 (dd, 1 H, J ) 8.8, 11.5 Hz), 5.75
(dd, 1 H, J ) 9.0, 11.3 Hz), 5.73 (dd, 1 H, J ) 7.6, 11.5 Hz),
5.02 (dd, 1 H, J ) 8.5, 11.3 Hz), 3.29 (s, 3 H, CH3). 31P NMR
(121 MHz): δ 24.7.
Tetr a sa cch a r id e 26. The aldehyde 7 (273 mg, 0.39 mmol)
was treated with 25 (508 mg, 0.30 mmol) as described for the
preparation of 22 to give 26 (554 mg, 93%) as a syrup. [R]D
)
-11.3 (c 1.2, CHCl3). 1H NMR (300 MHz) selected data: δ 5.83
(dd, 1 H, J ) 9.0, 11.6 Hz), 5.81-5.66 (4 dd, 4 H, 2 CHdCH),
5.63 (dd, 1 H, J ) 7.5, 11.4 Hz), 3.21 (s, 3 H, CH3). MALDI-
TOF MS (1988.56): m/z 2012.3 (M + Na), 2027.6 (M + K).
Anal. Calcd for C128H134O18Si: C, 77.31; H, 6.79. Found: C,
77.40; H, 6.88.
1
1,5-pyranoside (0.94 g). H NMR (300 MHz) selected data: δ
7.40-7.20 (m, 30 H, 6 Ph), 5.88 (dd, 1 H, J 5,6 ) 8.8, J 6,7 ) 11.7
Hz, H-6), 5.70 (dd, 1 H, J 7,8 ) 7.2 Hz, H-7), 4.69 (d, 1 H, J 1,2
)
3.2 Hz, H-1), 4.15 (dd, 1 H, J 10,11 ) 2.4, J 11,12 ) 0.5 Hz, H-11),
4.02 (dd, 1 H, J 2,3 ) 10.0 Hz, H-2), 4.01 (dd, 1 H, J 8,9 ) 9.3 Hz,
Tetr a sa cch a r id e 27. The tetrasaccharide 26 (398 mg, 0.20
mmol) was treated as described for the preparation of 25 to
give 27 (322 mg, 76%) slightly contaminated by triphenylphos-
phine. 1H NMR (300 MHz) selected data: δ 6.00 (dd, 1 H, J )
9.0, 12.0 Hz), 3.24 (s, 3 H, CH3). 31P NMR (121 MHz): δ 24.4.
P en ta sa cch a r id e 28. To a cooled (-20 °C), stirred mixture
of aldehyde 7 (91 mg, 0.13 mmol), iodide 27 (212 mg, 0.10
mmol), activated 4 Å powdered molecular sieves (130 mg),
anhydrous THF (3 mL), and anhydrous HMPA (1 mL) was
added a solution of n-BuLi (63 µL, 0.10 mmol, of a 1.6 M
solution in hexane) in anhydrous THF (0.3 mL) by a syringe-
pump apparatus over 4 h. After that period the reaction
mixture was diluted with Et2O (100 mL), filtered through a
pad of Celite, washed with 1 M phosphate buffer at pH 7 (20
mL), dried (Na2SO4), and concentrated. The residue was eluted
from a column of silica gel with 9:1 cyclohexane-AcOEt to give
H-8), 3.89 (dd, 1 H, J 3,4 ) 2.8 Hz, H-3), 3.77 (dd, 1 H, J 9,10
)
9.2 Hz, H-9), 3.71 (dd, 1 H, J 4,5 ) 0.5 Hz, H-4), 3.64 (dd, 1 H,
H-10), 3.54 (ddd, 1 H, J 12,13a ) 6.0, J 12,13b ) 7.2 Hz, H-12), 3.34
(s, 3 H, CH3), 3.18 (dd, 1 H, J 13a,13b ) 10.0 Hz, H-13a), 3.14
(dd, 1 H, H-13b). The iodide was treated with triphenylphos-
phine (2.46 g, 9.37 mmol) as described for the preparation of
20 to give 23 (1.11 g, 88%) as a white solid. Mp 213-214 °C
dec (CH3OH). [R]D ) +66.1 (c 0.6, CHCl3). 1H NMR (300 MHz)
selected data: δ 7.78-7.50 and 7.43-7.10 (2 m, 45 H, 9 Ph),
5.57 (dd, 1 H, J 5,6 ) 8.1, J 6,7 ) 11.5 Hz, H-6), 5.01 (dd, 1 H,
J 7,8 ) 8.5 Hz, H-7), 4.50 (d, 1 H, J 1,2 ) 3.5 Hz, H-1), 4.29 (dd,
1 H, J 4,5 ) 0.6 Hz, H-5), 3.92 (dd, 1 H, J 2,3 ) 10.0 Hz, H-2),
3.80 (dd, 1 H, J 8,9 ) 9.4 Hz, H-8), 3.76 (dd, 1 H, J 9,10 ) 9.1,
J 10,11 ) 1.6 Hz, H-10), 3.64 (dd, 1 H, J 3,4 ) 2.7 Hz, H-3), 3.56
(dd, 1 H, H-9), 3.29 (dd, 1 H, H-4), 3.08 (s, 3 H, CH3). 31P NMR
(121 MHz): δ 24.9. Anal. Calcd for C74H74IO9P (1265.28): C,
70.25; H, 5.90. Found: C, 70.42; H, 5.99.
1
28 (222 mg, 92%) as a syrup. [R]D ) -21.1 (c 1.1, CHCl3). H
NMR (300 MHz) selected data: δ 5.82 (dd, 2 H, J ) 8.8, 11.5
Hz), 5.75-5.61 (6 dd, 6 H, 3 CHdCH), 5.10 and 4.67 (2 d, 2 H,
J ) 11.5 Hz, PhCH2), 3.19 (s, 3 H, CH3), 1.04 (s, 9 H, t-Bu).
MALDI-TOF MS (2417.10): m/z 2439.8 (M + Na), 2456.2 (M
+ K). Anal. Calcd for C156H162O22Si: C, 77.52; H, 6.76. Found:
C, 77.76; H, 6.83.
Tr isa cch a r id e 24. The aldehyde 7 (420 mg, 0.60 mmol) was
treated with 23 (633 mg, 0.50 mmol) as described for the
preparation of 22 to give syrupy 24 (679 mg, 87%) slightly
contaminated by the Z,E-isomer. 1H NMR (300 MHz) selected
data: δ 5.86 (dd, 1 H, J 5,6 ) 8.3, J 6,7 ) 11.5 Hz, H-6), 5.83 (dd,
1 H, J 12,13 ) 8.4, J 13,14 ) 11.6 Hz, H-13), 5.71 (dd, 1 H, J 7,8
)
Meth yl 2,3,4,9,10,11,13-Hep ta -O-a cetyl-8,12-a n h yd r o-
6,7-d id eoxy-r-D-glycer o-L-m a n n o-D-ga la cto-t r id eco-1,5-
p yr a n osid e (29Ac). The disaccharide 22 (90 mg, 0.08 mmol)
was desilylated, hydrogenated, and acetylated as described for
the preparation of 15Ac to give, after column chromatography
(1:1 AcOEt-cyclohexane), 29Ac (43 mg, 82%) as a syrup. [R]D
) +58.5 (c 1.1, CHCl3). 1H NMR (C6D6, 300 MHz): δ 5.72 (dd,
1 H, J 2,3 ) 10.8, J 3,4 ) 3.3 Hz, H-3), 5.54 (dd, 1 H, J 1,2 ) 3.7
Hz, H-2), 5.53 (dd, 1 H, J 4,5 ) 1.0 Hz, H-4), 5.50 (dd, 1 H, J 10,11
7.5 Hz, H-7), 5.65 (dd, 1 H, J 14,15 ) 7.5 Hz, H-14), 4.73 (dd, 1
H, J 4,5 ) 0.5 Hz, H-5), 4.68 (d, 1 H, J 1,2 ) 3.6 Hz, H-1), 4.31
(dd, 1 H, J 11,12 ) 0.5 Hz, H-12), 4.00 (dd, 1 H, J 2,3 ) 10.1 Hz,
H-2), 3.98 (dd, 1 H, J 8,9 ) 9.5 Hz, H-8), 3.28 (s, 3 H, CH3).
MALDI-TOF MS (1560.03): m/z 1582.8 (M + Na), 1599.0 (M
+ K). Anal. Calcd for C100H106IO14Si: C, 76.99; H, 6.85.
Found: C, 76.81; H, 6.98.
Tr isa cch a r id e 25. A solution of 24 (624 mg, 0.40 mmol)
and n-Bu4NF.3H2O (310 mg, 1.20 mmol) in distilled THF (16
mL) was refluxed for 2 h, then cooled to rt, diluted with 1 M
phosphate buffer at pH 7 (20 mL), and extracted with Et2O (2
× 80 mL). The combined organic layers were dried (Na2SO4)
and concentrated. The residue was eluted from a column of
silica gel with cyclohexane-AcOEt (from 3:1 to 1:1.5) to give
the corresponding alcohol (510 mg) as the pure Z,Z-isomer.
[R]D ) +11.3 (c 0.9, CHCl3). 1H NMR (300 MHz) selected
data: δ 5.90 (dd, 1 H, J ) 8.5, 11.3 Hz), 5.88 (dd, 1 H, J ) 9.0,
12.0 Hz), 5.73 (dd, J ) 7.6, 11.3 Hz), 5.72 (dd, 1 H, J ) 7.8,
12.0 Hz), 3.33 (s, 3 H, CH3). To a vigorously stirred solution of
the alcohol, triphenylphosphine (203 mg, 0.78 mmol), and
imidazole (106 mg, 1.55 mmol) in anhydrous toluene (8 mL)
was added iodine (197 mg, 0.78 mmol). The mixture was
refluxed for 1 h, then cooled to rt, filtered through a pad of
Celite, and concentrated. A solution of the residue in CH2Cl2
(100 mL) was washed with 5% aqueous Na2S2O3 (2 × 30 mL),
dried (Na2SO4), and concentrated. Column chromatography of
the residue (2:1 CH2Cl2-cyclohexane, and then 6:1 cyclohex-
ane-AcOEt) gave the corresponding iodide (510 mg). 1H NMR
(300 MHz) selected data: δ 5.88 (dd, 2 H, J ) 8.9, 11.0 Hz),
5.73 (dd, 1 H, J ) 7.4, 11.0 Hz), 5.69 (dd, 1 H, J ) 7.3, 11.0
Hz), 3.33 (s, 3 H, CH3). A mixture of iodide and triphenylphos-
phine (0.94 g, 3.57 mmol) was stirred at 120 °C under a
nitrogen atmosphere for 4 h, and then cooled to room temper-
ature. The solid was triturated at rt with 4:1 cyclohexane-
Et2O (20 mL), and then cooled to 0 °C. After 15 min the
solution was removed, and the formed syrup was dried under
a vacuum to give 25 (557 mg, 82%) as an amorphous solid
) 3.3, J 11,12 ) 1.2 Hz, H-11), 5.42 (dd, 1 H, J 8,9 ) 9.6, J 9,10
10.2 Hz, H-9), 5.12 (dd, 1 H, H-10), 5.09 (d, 1 H, H-1), 4.08 (d,
2 H, J 12,13 ) 6.7 Hz, 2 H-13), 3.61 (ddd, 1 H, J 5,6a ) 4.5, J 5,6b
)
)
8.3 Hz, H-5), 3.32 (dt, 1 H, H-12), 3.13 (ddd, 1 H, J 7a,8 ) 2.5,
J 7b,8 ) 7.8 Hz, H-8), 3.00 (s, 3 H, OCH3), 1.73, 1.71, 1.69, 1.64,
and 1.59 (5 s, 21 H, 7 Ac). Anal. Calcd for C28H40O17 (648.63):
C, 51.85; H, 6.22. Found: C, 51.60; H, 6.41.
Tr isa cch a r id e 30Ac. The trisaccharide 24 (109 mg, 0.07
mmol) was desilylated, hydrogenated, and acetylated as
described for the preparation of 15Ac to give, after column
chromatography (2:1 AcOEt-cyclohexane), 30Ac (52 mg, 80%)
1
as a syrup. [R]D ) +15.5 (c 0.7, CHCl3). H NMR (300 MHz)
selected data: δ 5.42 (dd, 1 H, J ) 0.8, 3.0 Hz), 5.31 (dd, 2 H,
J
) 0.7, 3.2 Hz), 3.40 (s, 3 H, OCH3). MALDI-TOF MS
(934.91): m/z 958.2 (M + Na), 973.9 (M + K). Anal. Calcd for
C
41H58O24: C, 52.67; H, 6.25. Found: C, 52.58; H, 6.32.
Tetr a sa cch a r id e 31Ac. A solution of 26 (100 mg, 0.05
mmol) and n-Bu4NF.3H2O (47 mg, 0.15 mmol) in distilled THF
(5 mL) was refluxed for 2 h, then cooled to rt, diluted with 1
M phosphate buffer at pH 7 (10 mL), and extracted with Et2O
(2 × 50 mL). The combined organic layers were dried
(Na2SO4) and concentrated. The residue was eluted from a
column of silica gel with cyclohexane-AcOEt (from 3:1 to 2:1)
to give the corresponding alcohol. A vigorously stirred mixture
of this alcohol, 10% palladium on carbon (80 mg), and 1:1 CH3-
OH-AcOEt (5 mL) was degassed under
a vacuum and
saturated with hydrogen (by a H2-filled balloon) three times.
The suspension was stirred at rt for 6 h under a positive
pressure of hydrogen (7 bar), then filtered through a plug of

Synthesis of Oligoglucoses and Oligogalactoses
J . Org. Chem., Vol. 67, No. 12, 2002 4197
H-3), 4.11 (dd, 1 H, J 4,5 ) 9.0 Hz, H-4), 3.92 (dd, 1 H, J 5,6a
cotton, washed with distilled DMF, and concentrated to give
31. A solution of crude 31 in pyridine (2 mL) and acetic
anhydride (2 mL) was kept at rt for 8 h, and then concentrated.
The residue was eluted from a column of silica gel with 2:1
AcOEt-cyclohexane to give 31Ac (55 mg, 90%) as an amor-
)
3.2, J 6a,6b) 11.8 Hz, H-6a), 3.87-3.78 (m, 2 H, H-5, H-6b), 3.68
(d, 1 H, H-2), 2.25 (s, 3 H, Ac). Anal. Calcd for C43H41NO7S
(715.87): C, 72.15; H, 5.77; N, 1.96. Found: C, 72.24; H, 5.71;
N, 1.91. To a stirred mixture of acetate (5.73 g, 8.00 mmol),
activated 4 Å powdered molecular sieves (8.0 g), and trieth-
ylsilane (12.8 mL, 80.0 mmol) in anhydrous CH2Cl2 (65 mL)
was added TMSOTf (2.17 mL, 12.00 mmol). The mixture was
stirred at rt for 1.5 h, then diluted with triethylamine (3 mL)
and CH2Cl2 (100 mL), and filtered through Celite. The solution
was washed with H2O (30 mL), dried (Na2SO4), and concen-
trated to afford a ca. 1.5:1 mixture of 34 and its R-anomer.
The residue was triturated with cyclohexane (2 × 20 mL) to
give pure 34 (3.16 g, 60%) as a white solid. The mother liquor
was concentrated, and the residue was treated with a 0.2 M
solution of CH3ONa in CH3OH (50 mL). After 24 h at rt the
reaction mixture was neutralized with acetic acid, concen-
trated, diluted with CH2Cl2 (100 mL), washed with H2O (20
mL), dried (Na2SO4), and concentrated. The residue was
triturated with cyclohexane (2 × 10 mL) to give 34 (1.05 g,
20%) as a white solid. Mp 137-139 °C. [R]D ) -10.6 (c 0.8,
CHCl3). 1H NMR (300 MHz): δ 8.06-8.03 and 7.98-7.95 (2
m, 2 H, BTh), 7.58-7.00 (m, 22 H, 4 Ph, BTh), 4.98 and 4.92
(2 d, 2 H, J ) 11.0 Hz, PhCH2), 4.88 and 4.65 (2 d, 2 H, J )
10.8 Hz, PhCH2), 4.79 (d, 1 H, J 1,2 ) 9.2 Hz, H-1), 4.67 and
4.59 (2 d, 2 H, J ) 12.2 Hz, PhCH2), 4.56 and 4.26 (2 d, 2 H,
J ) 10.5 Hz, PhCH2), 3.94-3.76 (m, 5 H), 3.70 (ddd, 1 H, J 4,5
1
phous solid. [R]D ) +39.9 (c 1.0, CHCl3). H NMR (300 MHz)
selected data: δ 5.41 (dd, 1 H, J ) 0.6, 3.0 Hz), 3.38 (s, 3 H,
OCH3). MALDI-TOF MS (1221.20): m/z 1244.6 (M + Na),
1260.2 (M + K). Anal. Calcd for C54H76O31: C, 53.11; H, 6.27.
Found: C, 53.22; H, 6.30.
P en ta sa cch a r id e 32Ac. The pentasaccharide 28 (48 mg,
0.20 mmol) was desilylated, hydrogenated, and acetylated as
described for the preparation of 31Ac. The crude product was
eluted from a column of silica gel with AcOEt-cyclohexane
(from 2:1 to 4:1) to give 32Ac (26 mg, 86%) as an amorphous
solid. [R]D ) +32.8 (c 0.6, CHCl3). 1H NMR (500 MHz): δ 5.40
(dd, 1 H, J 3,4 ) 3.5, J 4,5 ) 1.1 Hz, H-4E), 5.34 (dd, 1 H, J 3,4
)
3.5, J 4,5 ) 0.7 Hz, H-4A), 5.31 (dd, 1 H, J 2,3 ) 10.8 Hz, H-3A),
5.28 (dd, 3 H, J 3,4 ) 3.5, J 4,5 ) 0.7 Hz, H-4B, H-4C, H-4D),
5.13 (dd, 1 H, J 1,2 ) 3.7, J 2,3 ) 10.6 Hz, H-2A), 5.06, 5.04, and
5.03 (3 dd, 4 H, J 1,2 ) 9.3, J 2,3 ) 10.3 Hz, H-2B, H-2C, H-2D,
H-2E), 4.99 (dd, 1 H, H-3E), 4.96, 4.95, and 4.94 (3 dd, 3 H,
H-3B, H-3C, H-3D), 4.96 (d, 1 H, H-1A), 4.11 (dd, 1 H, J 5,6a
)
6.8, J 6a,6b ) 11.4 Hz, H-6aE), 4.06 (dd, 1 H, J 5,6b ) 6.5 Hz,
H-6bE), 3.91 (ddd, 1 H, J 5,6a ) 6.0, J 5,6b ) 8.0 Hz, H-5A), 3.84
(ddd, 1 H, J 5,6a ) J 5,6b ) 6.5 Hz, H-5E), 3.52-3.48 (m, 3 H,
H-5B, H-5C, H-5D), 3.38 (s, 3 H, OCH3), 3.38 (ddd, 1 H, J )
2.0, 8.2, 9.3 Hz, H-1E), 3.32 and 3.30 (2 ddd, 3 H, J ) 2.0, 8.2,
9.3 Hz, H-1B, H-1C, H-1D), 2.18-1.96 (9 s, 48 H, 16 Ac), 1.72-
1.58 and 1.48-1.40 (2 m, 16 H, 4 CH2CH2). MALDI-TOF MS
(1507.49): m/z 1530.9 (M + Na), 1547.4 (M + K). Anal. Calcd
for C67H94O38: C, 53.38; H, 6.28. Found: C, 53.44; H, 6.35.
2-(2,3,4,6-Tetr a -O-ben zyl-â-D-glu cop yr a n osyl)ben zoth i-
a zole (34). To a cooled (-65 °C), stirred solution of n-BuLi
(22.1 mL, 35.35 mmol, of a 1.6 M solution in hexane) in
anhydrous Et2O (80 mL) was added dropwise a solution of
freshly distilled 2-benzothiazole (4.78 g, 35.35 mmol) in
anhydrous Et2O (40 mL) over a 30 min period. The yellow
solution was stirred at -65 °C for 30 min, and then a solution
of gluconolactone 33 (13.60 g, 25.25 mmol) in anhydrous Et2O
(80 mL) was added slowly (30 min). After an additional 1 h at
-65 °C the mixture was allowed to warm to -50 °C in 30 min,
then diluted with Et2O (200 mL), and poured into 200 mL of
a 1 M phosphate buffer at pH 7. The layers were separated,
and the organic phase was filtered to collect the benzothiaz-
olylketose which crystallized during the extraction. The white
solid was washed with H2O and Et2O (10 mL) and dried to
give pure 2,3,4,6-tetra-O-benzyl-1-C-(2-benzothiazolyl)-R-D-
glucopyranose (9.87 g, 58%). The combined organic layers were
dried (Na2SO4) and concentrated. The residue was eluted from
a column of silica gel with cyclohexane-AcOEt (from 4:1 to
3:1) to give the benzothiazolylketose (3.40 g, 20%) as a white
) 10.5, J 5,6a ) J 5,6b ) 3.2 Hz, H-5). Anal. Calcd for C41H39
-
NO5S (657.83): C, 74.86; H, 5.98; N, 2.13. Found: C, 74.92;
H, 5.95; N, 2.08.
2-(2,3,4-Tr i-O-b en zyl-6-O-ter t-b u t yld ip h en ylsilyl-â-D-
glu cop yr a n osyl)ben zoth ia zole (35). To a solution of 34
(4.60 g, 7.00 mmol) in acetic anhydride (50 mL) was added a
solution of 96% H2SO4 (0.7 mL) in acetic acid (24 mL). The
reaction mixture was kept at rt for 1.5 h, then diluted with
AcOEt (300 mL), washed with H2O (3 × 100 mL) and saturated
aqueous Na2CO3 (2 × 100 mL), dried (Na2SO4), and concen-
trated. The crude 6-O-acetylated derivative was treated with
a freshly prepared ∼0.1 M solution of CH3ONa in CH3OH (50
mL) at rt for 3 h, then neutralized with acetic acid, and
concentrated. The residue was eluted from a column of silica
gel with 2.5:1 cyclohexane-AcOEt to give 2-(2,3,4-tri-O-benzyl-
â-D-glucopyranosyl)benzothiazole (2.94 g) as a white solid. Mp
131-132 °C (Et2O). [R]D ) -23.4 (c 0.7, CHCl3). 1H NMR (300
MHz): δ 8.13-8.07 and 7.94-7.88 (2 m, 2 H, BTh), 7.65-6.90
(m, 17 H, 3 Ph, BTh), 5.00 and 4.94 (2 d, 2 H, J ) 10.5 Hz,
PhCH2), 4.83-4.77 (m, 1 H, H-1), 4.88 and 4.73 (2 d, 2 H, J )
10.5 Hz, PhCH2), 4.59 and 4.27 (2 d, 2 H, J ) 11.0 Hz, PhCH2),
3.98-3.72 (m, 5 H), 3.61 (ddd, 1 H, J 4,5 ) 10.0, J 5,6a ) 2.5,
J 5,6b ) 1.5 Hz, H-5). Anal. Calcd for C34H33NO5S (567.71): C,
71.93; H, 5.86; N, 2.47. Found: C, 72.02; H, 5.80; N, 2.36. To
a stirred solution of this alcohol in pyridine (50 mL) was added
tert-butylchlorodiphenylsilane (2.02 mL, 7.77 mmol). Stirring
was continued for an additional 16 h, and then the reaction
mixture was diluted with CH3OH (2 mL) and concentrated. A
solution of the residue in CH2Cl2 (200 mL) was washed with
1 M phosphate buffer at pH 7 (50 mL), dried (Na2SO4), and
concentrated. The residue was triturated with CH3CN (2 ×
10 mL) to give 35 (3.00 g, 53% from 34) as a white solid. The
mother liquor was concentrated and eluted from a column of
silica gel with 10:1 cyclohexane-AcOEt (containing 0.3%
triethylamine) to give 35 (0.67 g, 12% from 34) as a white solid.
Mp 125-126 °C (cyclohexane). [R]D ) +32.6 (c 0.9, CHCl3).
1H NMR (300 MHz): δ 8.13-8.07 and 7.94-7.88 (2 m, 2 H,
BTh), 7.85-7.00 (m, 27 H, 5 Ph, BTh), 4.99 and 4.82 (2 d, 2
H, J ) 11.0 Hz, PhCH2), 4.98 and 4.94 (2 d, 2 H, J ) 11.0 Hz,
PhCH2), 4.83 (d, 1 H, J 1,2 ) 9.5 Hz, H-1), 4.59 and 4.24 (2 d,
2 H, J ) 10.5 Hz, PhCH2), 4.07 (dd, 1 H, J 3,4 ) 9.3, J 4,5 ) 9.5
Hz, H-4), 4.04 (dd, 1 H, J 5,6a ) 2.8, J 6a,6b ) 11.5 Hz, H-6a),
3.99 (dd, 1 H, J 5,6b ) 2.0 Hz, H-6b), 3.92 (dd, 1 H, J 2,3 ) 9.0
Hz, H-3), 3.81 (dd, 1 H, H-2), 3.57 (ddd, 1 H, H-5), 1.11 (s, 9
H, t-Bu). Anal. Calcd for C50H51NO5SSi (806.11): C, 74.50; H,
6.38; N, 1.74. Found: C, 74.46; H, 6.57; N, 1.86.
1
solid. Mp 115-117 °C (Et2O). [R]D ) -19.7 (c 0.4, CHCl3). H
NMR (300 MHz): δ 8.16-8.05 and 7.92-7.86 (2 m, 2 H, BTh),
7.60-6.95 (m, 22 H, 4 Ph, BTh), 4.94 (s, 2 H, PhCH2), 4.71 (s,
1 H, OH), 4.89 and 4.67 (2 d, 2 H, J ) 11.0 Hz, PhCH2), 4.66
and 4.54 (2 d, 2 H, J ) 12.5 Hz, PhCH2), 4.61 and 4.31 (2 d, 2
H, J ) 11.0 Hz, PhCH2), 4.21 (ddd, 1 H, J 4,5 ) 1.8, J 5,6a ) 11.0,
J 5,6b ) 4.0 Hz, H-5), 4.07 (dd, 1 H, J 2,3 ) 10.5, J 3,4 ) 8.0 Hz,
H-3), 4.03 (d, 1 H, H-2), 3.86 (dd, 1 H, H-4), 3.83 (dd, 1 H,
J 6a,6b ) 11.5 Hz, H-6a), 3.66 (dd, 1 H, H-6b). Anal. Calcd for
C
41H39NO6S (673.83): C, 73.08; H, 5.83; N, 2.08. Found: C,
73.01; H, 5.90; N, 2.01. To a solution of the benzothiazolylke-
tose (5.60 g, 8.31 mmol) in anhydrous CH2Cl2 (50 mL) were
added at rt distilled triethylamine (15 mL) and acetic anhy-
dride (15 mL). The solution was kept at rt for 24 h, and then
concentrated. The residue was triturated with Et2O (2 × 20
mL) to give pure 1-O-acetyl-2,3,4,6-tetra-O-benzyl-1-C-(2-
benzothiazolyl)-R-D-glucopyranose (5.23 g, 88%). Mp 136-137
°C (cyclohexane). [R]D ) +27.0 (c 1.1, CHCl3). 1H NMR (300
MHz): δ 8.11-8.05 and 7.92-7.86 (2 m, 2 H, BTh), 7.55-7.00
(m, 22 H, 4 Ph, BTh), 4.99 and 4.93 (2 d, 2 H, J ) 11.0 Hz,
PhCH2), 4.90 and 4.68 (2 d, 2 H, J ) 10.5 Hz, PhCH2), 4.78
and 4.65 (2 d, 2 H, J ) 12.0 Hz, PhCH2), 4.51 and 4.28 (2 d, 2
H, J ) 11.0 Hz, PhCH2), 4.22 (dd, 1 H, J 2,3 ) J 3,4 ) 9.5 Hz,
2,6-An h yd r o-3,4,5-tr i-O-ben zyl-7-O-ter t-bu tyld ip h en yl-
silyl-a ld eh yd o-D-glycer o-D-gu lo-h ep top yr a n ose (36). Ben-

4198 J . Org. Chem., Vol. 67, No. 12, 2002
Dondoni et al.
zothiazolyl C-glucoside 35 (2.42 g, 3.00 mmol) was treated as
described for the preparation of 7. After a similar workup the
residue was eluted from a short column (3 × 10 cm, diameter
× height) of silica gel with 5:1 cyclohexane-AcOEt to afford
8,12-anhydro-2,3,4,9,10,11-hexa-O-benzyl-6,7,13-trideoxy-13-
iodo-R-D-glycero-D-gulo-D-gluco-tridec-6-(Z,E)-eno-1,5-pyrano-
side (537 mg). 1H NMR (300 MHz) selected data for the
Z-isomer: δ 5.72-5.67 (m, 2 H, H-6, H-7), 4.56 (d, 1 H, J 1,2
)
1
syrupy 36 (1.94 g, 92%) ca. 95% pure by H NMR analysis. 1H
3.5 Hz, H-1), 4.01 (dd, 1 H, J 2,3 ) 10.0, J 3,4 ) 8.5 Hz, H-3),
3.53 (dd, 1 H, H-2), 3.43 (s, 3 H, CH3). MALDI-TOF MS
(1002.99): m/z 1026.9 (M + Na), 1043.1 (M + K). A mixture
of iodide and triphenylphosphine (1.40 g, 53.50 mmol) was
stirred at 120 °C under a nitrogen atmosphere for 4 h, cooled
to rt, triturated with toluene (10 mL) and then Et2O (3 × 10
NMR (300 MHz): δ 9.62 (d, 1 H, J 1,2 ) 1.5 Hz, H-1), 7.55-
7.15 (m, 25 H, 5 Ph), 4.95 (s, 2 H, PhCH2), 4.94 and 4.81 (2 d,
2 H, J ) 11.0 Hz, PhCH2), 4.86 and 4.70 (2 d, 2 H, J ) 10.5
Hz, PhCH2), 4.02-3.97 (m, 2 H, 2 H-7), 3.89 (dd, 1 H, J 3,4
)
8.2, J 4,5 ) 9.0 Hz, H-4), 3.83 (dd, 1 H, J 2,3 ) 10.0 Hz, H-2),
3.81 (dd, 1 H, J 5,6 ) 9.5 Hz, H-5), 3.70 (dd, 1 H, H-3), 3.42
(ddd, 1 H, J 6,7a ) J 6,7b ) 2.0 Hz, H-6), 1.11 (s, 9 H, t-Bu).
Meth yl 8,12-An h yd r o-2,3,4,9,10,11-h exa -O-ben zyl-13-O-
ter t-bu tyld ip h en ylsilyl-6,7-d id eoxy-r-D-glycer o-D-gu lo-D-
glu co-tr id ec-6-(Z,E)-en o-1,5-p yr a n osid e (37). The aldehyde
36 (1.05 g, 1.50 mmol) was treated with 21 (0.84 g, 1.00 mmol)
as described for the preparation of 22 to give, after column
chromatography on silica gel (10:1 cyclohexane-AcOEt), syr-
upy 37 as a ca. 7:1 mixture of Z,E-isomers (0.95 g, 84%).
Analytical samples of (Z)-37 and (E)-37 were obtained by
column chromatography on silica gel (15:1 cyclohexane-
AcOEt). Eluted first was (Z)-37. [R]D ) +0.7 (c 1.5, CHCl3).
1H NMR (C6D6, 300 MHz): δ 8.05-6.95 (m, 40 H, 8 Ph), 5.80
1
mL), and dried to give 38 (570 mg, 56%) as a white solid. H
NMR (300 MHz) selected data for the Z-isomer: δ 5.47 (dd, 1
H, J 5,6 ) 5.0, J 6,7 ) 11.5 Hz, H-6), 5.12 (dd, 1 H, J 7,8 ) 5.5 Hz,
H-7), 4.57 (d, 1 H, J 1,2 ) 3.5 Hz, H-1), 3.86 (dd, 1 H, J 2,3 ) 9.5,
J 3,4 ) 9.0 Hz, H-3), 3.45 (dd, 1 H, H-2), 3.17 (dd, 1 H, J 4,5
)
10.0 Hz, H-4), 3.10 (s, 3 H, CH3). Anal. Calcd for C74H74IO9P
(1265.28): C, 70.25; H, 5.90. Found: C, 70.51; H, 6.04.
Tr isa cch a r id e 39. The aldehyde 36 (182 mg, 0.26 mmol)
was treated with 38 (253 mg, 0.20 mmol) as described for the
preparation of 22 to give, after column chromatography on
silica gel (6:1 cyclohexane-AcOEt), syrupy 39 as a ca. 1.5:1
mixture of Z,E-isomers (219 mg, 70%). 1H NMR (300 MHz)
selected data for the 6Z,13Z-isomer: δ 5.85 (dd, 1 H, J 5,6
)
(dd, 1 H, J 5,6 ) 7.0, J 6,7 ) 11.0 Hz, H-6), 5.72 (dd, 1 H, J 7,8
)
5.0, J 6,7 ) 11.0 Hz, H-6), 5.79 (dd, 1 H, J 7,8 ) 4.5 Hz, H-7),
5.78-5.71 (m, 2 H, H-13, H-14), 3.35 (s, 3 H, OCH3), 1.23 (s,
7.2 Hz, H-7), 5.11 and 4.95 (2 d, 2 H, J ) 11.5 Hz, PhCH2),
5.01 and 4.82 (2 d, 2 H, J ) 11.5 Hz, PhCH2), 4.94 (s, 2 H,
PhCH2), 4.80 (dd, 1 H, J 4,5 ) 10.0 Hz, H-5), 4.78 and 4.71 (2 d,
2 H, J ) 11.0 Hz, PhCH2), 4.75 and 4.64 (2 d, 2 H, J ) 11.5
Hz, PhCH2), 4.68 (d, 1 H, J 1,2 ) 3.5 Hz, H-1), 4.56 and 4.48 (2
d, 2 H, J ) 12.0 Hz, PhCH2), 4.50 (dd, 1 H, J 8,9 ) 9.0 Hz, H-8),
4.27 (dd, 1 H, J 2,3 ) 9.8, J 3,4 ) 8.8 Hz, H-3), 4.04 (dd, 1 H,
J 10,11 ) J 11,12 ) 9.5 Hz, H-11), 4.03 (dd, 1 H, J 12,13a ) 1.0, J 13a,13b
) 12.0 Hz, H-13a), 3.92 (dd, 1 H, J 12,13b ) 1.5 Hz, H-13b), 3.71
(dd, 1 H, J 9,10 ) 9.5 Hz, H-10), 3.57 (dd, 1 H, H-2), 3.47 (dd, 1
H, H-9), 3.41 (dd, 1 H, H-4), 3.20 (ddd, 1 H, H-12), 3.13 (s, 3
H, OCH3), 1.20 (s, 9 H, t-Bu). Anal. Calcd for C72H78O10Si
(1131.50): C, 76.43; H, 6.95. Found: C, 76.61; H, 7.04. Eluted
second was (E)-37. [R]D ) +5.0 (c 1.5, CHCl3). 1H NMR (C6D6,
300 MHz) selected data: δ 6.32 (dd, 1 H, J 6,7 ) 15.5, J 7,8 ) 5.5
1
9 H, t-Bu). H NMR (300 MHz) selected data for the 6Z,13E-
isomer: δ 6.31 (dd, 1 H, J ) 6.0, 16.0 Hz), 6.21 (dd, 1 H, J )
4.8, 16.0 Hz), 5.85 (dd, 1 H, J 5,6 ) 5.0, J 6,7 ) 11.0 Hz, H-6),
5.79 (dd, 1 H, J 7,8 ) 4.5 Hz, H-7), 3.40 (s, 3 H, CH3), 1.20 (s, 9
H, t-Bu). MALDI-TOF MS (1560.03): m/z 1582.8 (M + Na),
1599.4 (M + K). Anal. Calcd for C100H106IO14Si: C, 76.99; H,
6.85. Found: C, 77.36; H, 7.12.
Tr isa cch a r id e 40. The trisaccharide 39 (780 mg, 0.50
mmol) was treated as described for the preparation of 38. The
crude product was eluted from a column of silica gel with 1:1
CH2Cl2-acetone to give 40 (618 mg, 73%) as an amorphous
solid ca. 95% pure by TLC and NMR analysis.
Tetr a sa cch a r id e 41. The aldehyde 36 (363 mg, 0.52 mmol)
was treated with 40 (677 mg, 0.40 mmol) as described for the
preparation of 22 to give, after column chromatography on
silica gel (9:1 cyclohexane-AcOEt), 41 as a syrup (596 mg,
75%). MALDI-TOF MS (1988.56): m/z 2012.3 (M + Na), 2027.6
(M + K). Anal. Calcd for C128H134O18Si: C, 77.31; H, 6.79.
Found: C, 77.09; H, 6.90.
Tetr a sa cch a r id e 42. The tetrasaccharide 41 (595 mg, 0.30
mmol) was treated as described for the preparation of 38. The
crude product was eluted from a column of silica gel with 1:1
CH2Cl2-acetone to give 42 (396 mg, 62%) as an amorphous
solid ca. 95% pure by TLC and NMR analysis.
Hz, H-7), 6.24 (dd, 1 H, J 5,6 ) 4.5 Hz, H-6), 4.69 (d, 1 H, J 1,2
)
3.5 Hz, H-1), 4.43 (dd, 1 H, J 8,9 ) 9.3 Hz, H-8), 4.30 (dd, 1 H,
J 2,3 ) 9.5, J 3,4 ) 9.2 Hz, H-3), 4.04 (d, 2 H, J 12,13 ) 2.0 Hz, 2
H-13), 3.97 (dd, 1 H, J 10,11 ) 8.7, J 11,12 ) 9.0 Hz, H-11), 3.80
(dd, 1 H, J 4,5 ) 9.2 Hz, H-5), 3.69 (dd, 1 H, J 9,10 ) 9.3 Hz,
H-10), 3.62 (dd, 1 H, H-2), 3.42 (dd, 1 H, H-4), 3.37 (dd, 1 H,
H-9), 3.28 (dt, 1 H, H-12), 3.18 (s, 3 H, OCH3), 1.20 (s, 9 H,
t-Bu). MALDI-TOF MS (1131.50): m/z 1154.5 (M + Na), 1170.6
(M + K). Anal. Calcd for C72H78O10Si: C, 76.43; H, 6.95.
Found: C, 76.68; H, 7.06.
(Meth yl 8,12-a n h yd r o-2,3,4,9,10,11-h exa -O-ben zyl-6,7,-
13-tr id eoxy-r-D-glycer o-D-gu lo-D-glu co-tr id ec-6-(Z,E)-en o-
1,5-p yr a n osid -13-yl)tr ip h en ylp h osp h on iu m Iod id e (38).
A solution of 37 (905 mg, 0.80 mmol) and n-Bu4NF.3H2O (757
mg, 2.40 mmol) in distilled THF (16 mL) was refluxed for 2 h,
then cooled to rt, diluted with 1 M phosphate buffer at pH 7
(30 mL), and extracted with Et2O (2 × 100 mL). The combined
organic layers were dried (Na2SO4) and concentrated. The
residue was eluted from a column of silica gel with 2:1
cyclohexane-AcOEt to give methyl 8,12-anhydro-2,3,4,9,10,-
11-hexa-O-benzyl-6,7-dideoxy-R-D-glycero-D-gulo-D-gluco-tridec-
6-(Z,E)-eno-1,5-pyranoside (543 mg). 1H NMR (300 MHz)
selected data for the Z-isomer: δ 5.79 (dd, 1 H, J 5,6 ) 6.5, J 6,7
) 11.5 Hz, H-6), 5.61 (dd, 1 H, J 7,8 ) 8.5 Hz, H-7), 4.54 (d, 1
H, J 1,2 ) 3.5 Hz, H-1), 4.16 (dd, 1 H, J 4,5 ) 9.5 Hz, H-5), 3.41
(s, 3 H, CH3), 2.54 (dd, 1 H, J 13a,OH ) J 13b,OH ) 6.9 Hz, OH).
MALDI-TOF MS (893.10): m/z 915.5 (M + Na), 931.6 (M +
K). To a vigorously stirred solution of the alcohol, triphen-
ylphosphine (320 mg, 1.22 mmol), and imidazole (166 mg, 2.43
mmol) in anhydrous toluene (12 mL) was added iodine (310
mg, 1.22 mmol). The mixture was refluxed for 1 h, then cooled
to rt, filtered through a pad of Celite, and concentrated. A
solution of the residue in CH2Cl2 (100 mL) was washed with
5% aqueous Na2S2O3 (2 × 30 mL), dried (Na2SO4), and
concentrated. The residue was eluted from a column of silica
gel with CH2Cl2-cyclohexane (from 2:1 to 10:1) to give methyl
P en ta sa cch a r id e 43. The aldehyde 36 (91 mg, 0.13 mmol)
was treated with 42 (212 mg, 0.10 mmol) as described for the
preparation of 28 to give, after column chromatography on
silica gel (9:1 cyclohexane-AcOEt), 43 as a syrup (180 mg,
75%). MALDI-TOF MS (2417.10): m/z 2439.8 (M + Na), 2455.6
(M + K). Anal. Calcd for C156H162O22Si: C, 77.52; H, 6.76.
Found: C, 77.79; H, 6.88.
Meth yl 2,3,4,9,10,11,13-Hep ta -O-a cetyl-8,12-a n h yd r o-
6,7-d id eoxy-r-D-glycer o-D-gu lo-D-glu co-tr id eco-1,5-p yr a -
n osid e (44Ac). The disaccharide 37 (113 mg, 0.10 mmol) was
desilylated as described for the preparation of 38 to give, after
column chromatography (2:1 cyclohexane-AcOEt), methyl 8,-
12-anhydro-2,3,4,9,10,11-hexa-O-benzyl-6,7-dideoxy-R-D-glyc-
ero-D-gulo-D-gluco-tridec-6-(Z,E)-eno-1,5-pyranoside. A mixture
of this alcohol, 20% palladium hydroxide on carbon (100 mg),
and 1:1 CH3OH-AcOEt (5 mL) was degassed under a vacuum
and saturated with hydrogen (by a H2-filled balloon) three
times. The suspension was stirred at rt for 6 h under a positive
pressure of hydrogen (7 bar), then filtered through a plug of
cotton, washed with CH3OH and H2O, and concentrated to
give 44. [R]D ) +56.0 (c 0.8, CH3OH) (lit.5a [R]D ) +61 (c 0.6,
CH3OH); lit.27 [R]D ) +88 (c 1, CH3OH)). A solution of 44 and
(27) Rouzaud, D.; Sinay¨, P. J . Chem. Soc., Chem. Commun. 1983,
1353-1354.

Synthesis of Oligoglucoses and Oligogalactoses
J . Org. Chem., Vol. 67, No. 12, 2002 4199
4-(dimethylamino)pyridine (5 mg) in pyridine (2 mL) and acetic
anhydride (2 mL) was kept at rt for 8 h, and then concentrated.
The residue was eluted from a column of silica gel with 1:1
cyclohexane-AcOEt to give 44Ac (57 mg, 88%) as a white
solid. Mp 175-176 °C (AcOEt-cyclohexane). [R]D ) +69.5 (c
0.9, CHCl3) (lit.27 mp 172 °C). [R]D ) +55 (c 1, CHCl3) (lit.5m
mp 166-168 °C). [R]D ) +15.3 (c 0.6, CHCl3) (lit.5h [R]D ) +65
mL) was kept at rt for 12 h, and then concentrated. The residue
was eluted from a column of silica gel with 1:1 cyclohexane-
AcOEt to give 46Ac (34 mg, 69%) as a white solid. Mp 86-90
1
°C (AcOEt-cyclohexane). [R]D ) +30 (c 0.3, CHCl3). H NMR
(300 MHz) selected data: δ 5.45 (dd, 1 H, J 2,3 ) J 3,4 ) 9.5 Hz,
H-3), 4.22 (dd, 1 H, J 26,27a ) 2.5, J 27a,27b ) 12.0 Hz, H-27a),
4,10 (dd, 1 H, J 26,27b ) 5.5 Hz, H-27b), 3.74-3.71 (m, 1 H, H-5),
3.65 (ddd, 1 H, H-26), 2.13-1.99 (13 s, 39 H, 13 Ac). MALDI-
TOF MS (1221.20): m/z 1244.0 (M + Na), 1260.3 (M + K).
Anal. Calcd for C54H76O31: C, 53.11; H, 6.27. Found: C, 53.34;
H, 6.38.
1
(c 0.5, CHCl3); lit.5a [R]D ) +63 (c 0.7, CHCl3)). H NMR (300
MHz): δ 5.42 (dd, 1 H, J 2,3 )J 3,4 ) 9.8 Hz, H-3), 5.16 (dd, 1 H,
J 9,10 ) J 10,11 ) 9.5 Hz, H-10), 5.02 (dd, 1 H, J 11,12 ) 9.7 Hz,
H-11), 4.90-4.79 (m, 4 H), 4.23 (dd, 1 H, J 12,13a ) 5.5, J 13a,13b
) 12.5 Hz, H-13a), 4.07 (dd, 1 H, J 12,13b ) 2.0 Hz, H-13b), 3,73
(ddd, 1 H, J 4,5 ) 9.5, J 5,6a ) 7.0, J 5,6b ) 1.5 Hz, H-5), 3.61 (ddd,
1 H, H-12), 3.38 (ddd, 1 H, J 7a,8 ) 10.0, J 7b,8 ) 1.0, J 8,9 ) 9.0
Hz, H-8), 3.35 (s, 3 H, OCH3), 2.10-1.99 (7 s, 21 H, 7 Ac), 1.84-
1.74 and 1.46-1.38 (2 m, 4 H, 2 H-6, 2 H-7). Anal. Calcd for
C28H40O17 (648.63): C, 51.85; H, 6.22. Found: C, 51.72; H, 6.20.
Tr isa cch a r id e 45Ac. The trisaccharide 39 (78 mg, 0.05
mmol) was desilylated as described for the preparation of 40.
A mixture of the resulting alcohol, 20% palladium hydroxide
on carbon (70 mg), and 1:1 CH3OH-AcOEt (5 mL) was
degassed under a vacuum and saturated with hydrogen (by a
H2-filled balloon) three times. The suspension was stirred at
rt for 8 h under a positive pressure of hydrogen (7 bar), then
filtered through a plug of cotton, washed with distilled DMF
and H2O, and concentrated to give 45 as an amorphous solid.
[R]D ) +40.5 (c 0.4, H2O). A solution of 45 and 4-(dimeth-
ylamino)pyridine (5 mg) in pyridine (2 mL) and acetic anhy-
dride (2 mL) was kept at rt for 12 h, and then concentrated.
The residue was eluted from a column of silica gel with
cyclohexane-AcOEt (from 1:1 to 1:2) to give 45Ac (38 mg, 81%)
as a white solid. Mp 168-169 °C (AcOEt-cyclohexane). [R]D
P en ta sa cch a r id e 47Ac. The pentasaccharide 43 (73 mg,
0.03 mmol) was desilylated and hydrogenated as described for
the preparation of 45 to give 47 as an amorphous solid. [R]D
)
+6.3 (c 0.3, H2O). A solution of 47 and 4-(dimethylamino)-
pyridine (5 mg) in pyridine (1 mL) and acetic anhydride (1
mL) was kept at rt for 16 h, and then concentrated. The residue
was eluted from a column of silica gel with 2:1 AcOEt-
cyclohexane to give 47Ac (28 mg, 60%) as a white solid. Mp
196-198 °C (CH3OH). [R]D ) +24.4 (c 0.4, CHCl3). 1H NMR
(500 MHz) selected data: δ 5.43 (dd, 1 H, J 2,3 ) 9.9, J 3,4 ) 9.4
Hz, H-3A), 5.17 (dd, 1 H, J 2,3 ) J 3,4 ) 9.4 Hz, H-3E), 5.11 and
5.10 (2 dd, 3 H, J 2,3 ) J 3,4 ) 9.4 Hz, H-3B, H-3C, H-3D), 5.03
(dd, 1 H, J 4,5 ) 10.1 Hz, H-4E), 4.89 (d, 1 H, J 1,2 ) 3.7 Hz,
H-1A), 4.88 (dd, 1 H, J 1,2 ) 9.9 Hz, H-2E), 4.87 (dd, 1 H, J 4,5
) 9.6 Hz, H-4A), 4.86 (dd, 1 H, H-2A), 4.83, 4.82, 4.81, and
4.80 (4 dd, 6 H, J ) 9.5, 9.5 Hz, H-2B, H-2C, H-2D, H-4B,
H-4C, H-4D), 4.20 (dd, 1 H, J 5,6a ) 5.6, J 6a,6b ) 12.2 Hz, H-6aE),
4.10 (dd, 1 H, J 5,6b ) 2.3 Hz, H-6bE), 3.71 (ddd, 1 H, J 5,6a
)
2.0, J 5,6b ) 8.5 Hz, H-5A), 3.64 (ddd, 1 H, H-5E), 3.37 (s, 3 H,
OCH3), 2.10-1.99 (14 s, 48 H, 16 Ac). MALDI-TOF MS
(1507.49): m/z 1530.4 (M + Na), 1547.1 (M + K). Anal. Calcd
for C67H94O38: C, 53.38; H, 6.28. Found: C, 53.50; H, 6.33.
1
) +37.1 (c 1.1, CHCl3). H NMR (300 MHz) selected data: δ
5.45 (dd, 1 H, J 2,3 ) 10.0, J 3,4 ) 10.5 Hz, H-3), 5.06 (dd, 1 H,
J 17,18 ) 9.0, J 18,19 ) 10.5 Hz, H-18), 4.84 (dd, 1 H, J 1,2 ) 5.5
Hz, H-2), 4.24 (dd, 1 H, J 19,20a ) 5.0, J 20a,20b ) 12.5 Hz, H-20a),
4.12 (dd, 1 H, J 19,20b ) 2.5 Hz, H-20b), 3.65 (ddd, 1 H, H-19),
3.37 (s, 3 H, OCH3), 2.13-1.99 (10 s, 30 H, 10 Ac). MALDI-
TOF MS (934.91): m/z 958.0 (M + Na), 974.4 (M + K). Anal.
Calcd for C41H58O24: C, 52.67; H, 6.25. Found: C, 52.79; H,
6.30.
Ack n ow led gm en t. Generous financial support from
MURST-COFIN-2000 (Italy) is gratefully acknowledged.
We thank Mr. Paolo Formaglio (University of Ferrara)
for assistance in the NMR measurements and Dr. Carla
Marchiorro (GlaxoWellcome Medicines Research Labo-
ratory, Verona, Italy) for the 500 MHz NMR experi-
ments. Thanks are due to Dr. M. Kleban and Dr. H. M.
Zuurmond for exploratory work on route A, and to Ms.
M. Bovolenta for some experiments on route B.
Tet r a sa cch a r id e 46Ac. The tetrasaccharide 41 (80 mg,
0.04 mmol) was desilylated and hydrogenated as described for
the preparation of 45 to give 46 as an amorphous solid. [R]D
)
+32 (c 0.5, H2O). A solution of 46 and 4-(dimethylamino)-
pyridine (10 mg) in pyridine (2 mL) and acetic anhydride (2
J O011142U