2,3-Anhydrosugars in glycoside bond synthesis. Application to the preparation of C-2 functionalized α-D-arabinofuranosides

Article abstract of DOI:10.1016/j.tet.2003.12.022

A novel two-step route has been developed for the synthesis of a panel of oligosaccharides (9-17) containing C-2 functionalized α-D- arabinofuranosyl residues. The first step in this route consists of a highly stereocontrolled glycosylation reaction using

Full text of DOI:10.1016/j.tet.2003.12.022

Tetrahedron 60 (2004) 1481–1489
2,3-Anhydrosugars in glycoside bond synthesis. Application to the
preparation of C-2 functionalized a-D-arabinofuranosides
†
,
*
Oana M. Cociorva and Todd L. Lowary
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH 43210, USA
Received 17 November 2003; revised 9 December 2003; accepted 9 December 2003
Abstract—A novel two-step route has been developed for the synthesis of a panel of oligosaccharides (9–17) containing C-2 functionalized
a-D-arabinofuranosyl residues. The first step in this route consists of a highly stereocontrolled glycosylation reaction using a 2,3-
anhydrosugar thioglycoside (6). In the second step, the epoxide ring in the 2,3-anhydrosugar glycoside is regioselectively opened at C-2 with
sodium methoxide and sodium azide thus providing products with the a-D-arabinofuranosyl stereochemistry. This approach to these targets
circumvents the potential stereocontrol problems inherent in glycosylations with arabinofuranosyl donors possessing non-participating
groups at C-2. The route is also highly convergent, allowing the preparation of a range of C-20 and C-200 modified oligosaccharides upon
reaction of epoxy glycosides 27–29 with nucleophiles.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
Over the past few years we have reported1 syntheses of
arabinofuranosyl-containing oligosaccharides that are
fragments of two polysaccharides (arabinogalactan and
lipoarabinomannan) found in the cell wall of mycobacteria,
including the human pathogens Mycobacterium tuberculosis
and Mycobacterium leprae.2 These synthetic investigations
were carried out with the goal of developing routes that
would efficiently provide multi-milligram quantities of
material for subsequent biochemical studies, including the
identification of inhibitors of the enzymes that assemble
these cell wall polysaccharides. To date, we have prepared a
number of oligosaccharides, the largest of which is
hexasaccharide 1 (Chart 1). The glycan portion of 1 is a
key structural motif in both mycobacterial arabinogalactan
and lipoarabinomannan.1,2 These synthetic glycans have
found application in studies directed towards probing the
substrate specificity of mycobacterial arabinosyltransferases
(AraT’s)3 as well as in investigations dedicated to mapping
the specificities of antibodies that are generated against
mycobacterial cell wall polysaccharides.4
As part of these investigations, we needed to synthesize di-
and trisaccharide analogs in which the C-2 hydroxyl group
Keywords: Oligosaccharides; Arabinofuranosides; Anhydrosugars;
Glycosylation methodology.
*
Corresponding author. Tel.: þ1-7804921861; fax: þ1-7804927705;
e-mail address: tlowary@ualberta.ca
Present address: Department of Chemistry and Alberta Ingenuity Centre
†
for Carbohydrate Science, Gunning-Lemieux Chemistry Centre,
University of Alberta, Edmonton, Alta, Canada T6G 2G2.
Chart 1.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.12.022

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O. M. Cociorva, T. L. Lowary / Tetrahedron 60 (2004) 1481–1489
in the non-reducing sugar residues (positions C-20 and C-200)
was replaced with various other functionalities such as
amino or methoxy groups (e.g., 2, Chart 1). We envisioned
that such compounds would be potential inhibitors of the
AraT’s responsible for the installation of the b-(1!2)-
linked residues present in hexasaccharide 1, due to the
absence of the reactive hydroxyl group(s) that would serve
as the attachment point of the b-arabinofuranosyl residues
(rings E and F). We also envisioned, however, that their
stereocontrolled preparation by standard methods used in
oligosaccharide synthesis would be problematic. For
example, using conventional synthetic methodology, the
most straightforward approach to 2 would likely involve the
preparation of a 2-methoxy glycosyl donor (e.g., 3, Fig. 1),
which could be coupled with the appropriate acceptor
species, 4. A significant problem with this route is that
thioglycoside 2 has a non-participating group at C-2 and
thus the glycosylation will not benefit from the formation of
an acyloxonium ion intermediate that would ensure good
1,2-trans selectivity. The product (5) will almost certainly
be formed as a mixture of four chromatographically similar
diastereomers. Although in pyranose systems it is some-
times possible to obtain good 1,2-trans stereoselectivity in
the absence of a C-2 participating group in the donor
(usually in the preparation of a-mannopyranosides),5 our
experience with arabinofuranosides suggests that these
reactions will give a/b mixtures of products, which are
generally difficult to separate.1d,6 While it is not difficult to
imagine ways to circumvent this problem using conven-
tional synthetic methods, these approaches would be less
efficient. For example, a donor that would allow methylation
following the glycosylation could be used, or an a-ribo-
furanoside could be synthesized and then the stereo-
chemistry at C-20 and C-200 inverted.
We have discovered recently that 2,3-anhydrosugars
thioglycosides and glycosyl sulfoxides are efficient glyco-
sylating agents, providing glycosides with extremely high
stereocontrol.7 The major product formed from these
reactions is the one in which the newly formed glycosidic
bond is cis to the epoxide ring. Thus, glycosylation of
alcohols by thioglycoside 67b (Fig. 2) affords the a-glyco-
side 7 as the major product. We have further demonstrated
that the products of these glycosylations undergo regio-
selective nucleophilic ring opening of the epoxide at C-2,
affording products with the a-D-arabino stereochemistry (8,
Fig. 2).8 Based on these previous results, it appeared to us
that this methodology was ideally suited for the synthesis of
C-2 modified a-D-arabinofuranosides. In this paper, we
describe the synthesis of oligosaccharides 9–17 (Chart 2)
using our 2,3-anhydrosugar methodology. Oligosaccharide
analogs in which specific hydroxyl groups have been
modified through substitution with various functional
groups (e.g., O-methyl, amino, fluoro, or azido) have
Figure 1. Stereocontrol problem in the synthesis of 5 via the use of a 2-O-methylated thioglycoside, 3.
Figure 2. Use of 2,3-anhydrosugar thioglycoside 6 in the synthesis of a-arabinofuranosides (8).
Chart 2.

O. M. Cociorva, T. L. Lowary / Tetrahedron 60 (2004) 1481–1489
1483
previously been demonstrated to be inhibitors of glycosyl-
transferases from mammalian systems9 as well as those
from mycobacteria.10
range of C-20 and C-200 modified arabinofuranosyl oligo-
saccharides through reaction with appropriate nucleophiles.
2.1. Synthesis of monosaccharide building blocks
Thioglycoside 6 was synthesized in eight steps from
D-xylose as previously described.7b The acceptors 20, 22,
and 23 were prepared without incident from octyl a-D-
arabinofuranoside 1811 as illustrated in Scheme 1. Treat-
ment of 18 with triphenylmethyl chloride and pyridine in
dichloromethane followed by benzoyl chloride gave 19 in
97% yield. Removal of the trityl group with p-toluene-
sulfonic acid in methanol/dichloromethane proceeded in
94% yield to afford 20. Alternatively, reaction of 18 with
1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in pyridine,
followed by the addition of benozyl chloride provided the
fully protected arabinofuranoside 21 in 89% yield.
Subsequent cleavage of the siloxane protecting group with
n-Bu4NF was achieved in 92% yield to provide diol 22. The
2. Results and discussion
Shown in Figure 3 is the retrosynthetic analysis of the
targets. We envisioned that all of the desired compounds
could be obtained from one of three anhydrosugar-contain-
ing oligosaccharides (27–29), which in turn could be
prepared from four monosaccharide building blocks: 6, 20,
22, and 23. In addition to circumventing the previously
mentioned stereocontrol problems, another advantage of
this approach over more conventional ones (e.g., the
preparation of a series of C-2 modified monosaccharide
donors) is that it is highly convergent. Anhydrosugar
glycosides 27–29 could be used as precursors to a wide
Figure 3. Retrosynthetic analysis of 9–17.
Scheme 1. (a) TrCl, pyridine, CH2Cl2, rt, then BzCl, rt 97% (two steps, one pot). (b) p-TsOH, CH2Cl2, CH3OH, rt, 94%. (c) 1,3-Dichloro-1,1,3,3-
tetraisopropyldisiloxane, pyridine, rt, then BzCl, rt 89% (two steps, one pot). (d) n-Bu4NF, THF, rt, 92%. (e) BzOH, Ph3P, DEAD, THF, rt, 93%.

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O. M. Cociorva, T. L. Lowary / Tetrahedron 60 (2004) 1481–1489
Scheme 2. (a) 6, N-iodosuccinimide, AgOSO2CF3, CH2Cl2, 240 8C, 84% (for 20), 89% (for 23) 75% (for 22). (b) NaOCH3, CH3OH, rt, 92% (for 24), 98% (for
25), 89% (for 26).
1
remaining acceptor, 23, was obtained in one step and 93%
yield from 22 upon Mitsunobu reaction with benzoic acid.
appeared in the H NMR spectrum as a singlet or small
doublet (3JH1,H2,2.2 Hz), while the anomeric carbon of
these residues appeared in the 13C NMR spectrum between
105 and 109 ppm. These data are consistent with the
a-arabino stereochemistry in the products.14 Attack of
the nucleophile at C-3 would have led to products with the
a-xylo stereochemistry, in which the anomeric hydrogens
would have appeared in the 1H NMR spectrum as a doublet
2.2. Glycosylation reactions and deprotection
With the four monosaccharides in hand, thioglycoside 6 was
used to glycosylate alcohols 20, 22, and 23 (Scheme 2).
These reactions were carried out using our standard
protocol,7b which involves the coupling of the thioglycoside
and acceptor in dichloromethane at 240 8C using activation
by N-iodosuccinimide and silver triflate.12 The products 24,
25 and 26 were obtained in 84, 89, and 75% yield,
respectively. The anomeric stereochemistry in the 2,3-
anhydrosugar residues was determined by measuring the
3
with JH1,H2.4 Hz and the anomeric carbon resonance
would have appeared in the 13C NMR spectrum between
100 and 104 ppm.14 We also explored the use of NOE
spectroscopy to provide further support for the identity of
the ring-opened products. However, as might be expected
given the inherent flexibility of five-membered rings, only
weak intra-residue NOE’s were observed. For example, for
9, a very weak NOE was observed between H-20 and H-40
and0somewhat larger NOE was seen between H-30 and the
H-5 s. These NOE’s were consistent with the structures
determined using other NMR parameters, but their small
magnitudes provided little additional insight into the
product structures.
magnitude of 1JC-1,H-1 13 We have previously demonstrated
.
that this parameter is the only reliable method for
establishing anomeric stereochemistry in these 2,3-anhydro-
sugar derivatives.13 In none of the glycosylations did we
isolate any products with the b-stereochemistry and the
substrates required for the ring opening reactions, 27–29,
were obtained in 89–98% yield by treatment of 24–26 with
sodium methoxide.
In those reactions for which the yields are modest, we saw
no evidence of formation of products with the a-xylo
stereochemistry. Instead, the remainder of the mass balance
was unreacted starting material. We found that at prolonged
reaction times that some substrate decomposition began to
occur and therefore it was advantageous to stop the reaction
before all of the starting material was gone. The final
targets, the amino oligosaccharides 15–17, were obtained in
63–81% yield upon reduction of 12–14 with triphenyl-
phosphine and water.
2.3. Epoxide ring opening reactions
Introduction of the functionality at the C-20 and C-200
positions was achieved by heating each of 27–29 in the
presence of a nucleophile (Scheme 3). Similar to other 2,3-
anhydrosugars,7b,8 the epoxide moiety in these molecules is
quite robust and vigorous conditions are required for the
reactions to proceed at reasonable rates. Reaction of 27–29
with sodium methoxide in methanol at reflux afforded the
2-methoxy derivatives 9–11 in yields of 60–82%.
Similarly, the azido group was introduced upon heating a
solution of the epoxide at reflux in a 3:2 mixture of ethanol
and water containing sodium azide and ammonium chloride.
Under these conditions, 27–29 provided the corresponding
C-20 and C-200 azidosugar-containing oligosaccharides
12–14 in 54–60% yield.
3. Conclusions
In conclusion, we describe here efficient syntheses of
oligosaccharides containing C-2 modified a-arabino-
furanosyl residues (9–17). The method we have used for
the synthesis of these glycans involves a two-step process
that combines a highly stereocontrolled glycosylation
reaction of a 2,3-anhydrosugar thioglycoside (6) with a
highly regioselective epoxide ring opening reaction. This
In all cases, the structures of the products could be easily
confirmed by 1H and 13C NMR spectroscopy. For all
products the anomeric hydrogen in the ring-opened residues

O. M. Cociorva, T. L. Lowary / Tetrahedron 60 (2004) 1481–1489
1485
Scheme 3. (a) NaOCH3, CH3OH, reflux, 82% (for 27), 71% (for 28), 60% (for 29). (b) NaN3, NH4CL, EtOH, H2O, reflux, 60% (for 27), 54% (for 28), 56% (for
29). (c) Ph3P, H2O, THF, rt, 70% (for 12), 63% (for 13), 81% (for 14).
1
approach circumvents the potential stereocontrol problems
inherent in glycosylations with arabinofuranose donors with
non-participating groups at C-2.1d,6 Furthermore, this route
is highly convergent, allowing the preparation of a range of
C-20 and C-200 modified oligosaccharides upon reaction of
27–29 with any given nucleophile. In its present form, the
method is somewhat limited by the vigorous conditions
required to open the epoxide moieties and we are currently
investigating methods by which these reactions can be made
to proceed at lower temperatures. The testing of 27–29 as
inhibitors of mycobacterial AraT’s is in progress and will be
reported separately.
measured at 22^2 8C. H NMR spectra were recorded at
400 or 500 MHz and chemical shifts are referenced to either
TMS (0.0, CDCl3) or HOD (4.78, D2O). 13C NMR spectra
were recorded at 100 or 125 MHz and 13C chemical shifts
were referenced to internal CDCl3 (77.23, CDCl3) or
external dioxane (67.40, D2O). Electrospray mass spectra
were recorded on samples suspended in mixtures of THF
and CH3OH with added NaCl.
4.1.1. Octyl 5-O-(2-O-methyl-a-D-arabinofuranosyl)-a-
D-arabinofuranoside (9). To a solution of 27 (60 mg,
0.15 mmol) in dry CH3OH (10 mL), was added a 1 M
solution of NaOCH3 in CH3OH (3 mL, 3 mmol). The
reaction mixture was heated at reflux for 24 h, then cooled
and neutralized with acetic acid (0.2 mL). The solution was
concentrated and purified by chromatography (CH2Cl2/
CH3OH, 10:1) to give 9 (50 mg, 82%) as a colorless oil: Rf
0.67 (CH2Cl2/CH3OH, 6:1); [a]D þ71.9 (c 0.9, CH3OH); 1H
NMR (400 MHz, D2O, dH) 5.12 (s, 1H), 4.96 (s, 1H), 4.26
(s, 1H), 4.13–4.09 (m, 2H), 4.07–4.02 (m, 2H), 3.87–3.83
(m, 2H), 3.79–3.70 (m, 3H), 3.55–3.47 (m, 2H), 3.48 (s,
3H), 1.67–1.65 (m, 2H), 1.35–1.33 (m, 10H), 0.89–0.87
(m, 3H); 13C NMR (100 MHz, D2O, dC) 107.4, 105.5, 87.4,
83.7, 82.2, 81.8, 78.8, 77.2, 68.6, 66.7, 61.1, 57.9, 33.2, 29.8
(2), 29.7, 26.3, 22.9, 14.2; HR-ESI-MS calcd for
[C19H36O9]Naþ 431.2251, found 431.2261.
4. Experimental
4.1. General methods
Solvents were distilled from appropriate drying agents
before use. Unless stated otherwise, all reactions were
carried out at room temperature and under a positive
pressure of argon and were monitored by TLC on silica gel
60 F254. Spots were detected under UV light or by charring
with 10% H2SO4, in EtOH. Unless otherwise indicated, all
column chromatography was performed on silica gel 60
(40–60 mM). Iatrobeads refers to a beaded silica gel 6RS-
8060, which is manufactured by Iatron Laboratories
(Tokyo). The ratio between silica gel and crude product
ranged from 100 to 50:1 (w/w). Optical rotations were
4.1.2. Octyl 3-O-(2-O-methyl-a-D-arabinofuranosyl)-a-
D-arabinofuranoside (10). Epoxide 28 (35 mg, 0.09 mmol)

1486
O. M. Cociorva, T. L. Lowary / Tetrahedron 60 (2004) 1481–1489
was dissolved in CH3OH (10 mL) and treated with a 1 M
solution of NaOCH3 in CH3OH (3 mL, 0.3 mmol) as
described for the preparation of 9. The product was purified
by chromatography (CH2Cl2/CH3OH, 10:1) to give 10
(25 mg, 71%) as a colorless oil: Rf 0.81 (CH2Cl2/CH3OH,
6:1); [a]D þ92.5 (c 0.8, CH3OH); 1H NMR (500 MHz, D2O,
dH) 5.17 (d, 1H, J¼1.4 Hz), 4.94 (s, 1H), 4.15 (s, 1H), 4.06–
4.02 (m, 2H), 3.96–3.92 (m, 2H), 3.81–3.77 (m, 2H), 3.74–
3.72 (m, 2H), 3.71–3.62 (m, 3H), 3.41 (s, 3H), 1.56–1.52
(m, 2H), 1.27–1.26 (m, 10H), 0.86–0.83 (m, 3H); 13C NMR
(125 MHz, D2O, dC) 108.1, 105.0, 91.8, 83.3, 83.2, 83.0,
82.1, 80.1, 74.9, 68.1, 61.2, 57.8, 32.2, 29.7 (2), 29.6, 26.3,
22.9, 14.2; HR-ESI-MS calcd for [C19H36O9]Naþ 431.2251,
found 431.2233.
1.59–1.54 (m, 2H), 1.29–1.27 (m, 10H), 0.90–0.86 (m,
3H); 13C NMR (100 MHz, CDCl3, dC) 108.0, 104.9, 84.5,
82.7, 82.5, 79.9, 75.2, 71.4, 68.0, 61.6, 61.1, 31.9, 29.5,
29.4, 29.3, 26.1, 22.7, 14.1; HR-ESI-MS calcd for
[C18H33O8N3]Naþ 442.2160, found 442.2166.
4.1.6. Octyl 3,5-di-O-(2-azido-2-deoxy-a-D-arabino-
furanosyl)-a-D-arabinofuranoside (14). Epoxide 29
(33 mg, 0.06 mmol) was treated as described for the
preparation of 12 with NaN3 (330 mg, 6.5 mmol) and
NH4Cl (350 mg, 6.5 mmol) in ethanol (15 mL) and water
(10 mL). The product was purified by chromatography
(CH2Cl2/CH3OH, 10:1) to give 14 (20 mg, 56%) as a
colorless oil: Rf 0.35 (CH2Cl2/CH3OH, 10:1); [a]D þ75.6 (c
1
0.8, CH3OH); H NMR (400 MHz, D2O, dH) 5.13 (d, 1H,
4.1.3. Octyl 3,5-di-O-(2-O-methyl-a-D-arabinofurano-
syl)-a-D-arabinofuranoside (11). Epoxide 29 (32 mg,
0.06 mmol) was dissolved in CH3OH (10 mL) and treated
with a 1 M solution of NaOCH3 in CH3OH (3 mL,
0.3 mmol) as described for the preparation of 9. The
product was purified by chromatography (CH2Cl2/CH3OH,
10:1) to give 11 (20 mg, 60%) as a colorless oil: Rf 0.65
J¼1.9 Hz), 5.07 (d, 1H, J¼2.1 Hz), 4.97 (s, 1H), 4.23–4.20
(m, 2H), 4.17–4.14 (m, 1H), 4.08–4.04 (m, 4H), 3.91–3.89
(m, 1H), 3.83–3.79 (m, 4H), 3.71–3.63 (m, 4H), 3.34–3.33
(m, 1H), 1.53–1.50 (m, 2H), 1.15–1.11 (m, 10H), 0.83–
0.80 (m, 3H); 13C NMR (100 MHz, D2O, dC) 108.5, 105.2,
104.9, 84.0, 83.7, 81.9, 81.6, 81.4, 78.7, 69.3, 67.8, 67.5,
65.5, 61.6, 61.1, 33.3, 31.2, 31.0, 30.9, 30.8, 27.5, 24.1,
15.6; HR-ESI-MS calcd for [C23H40O11N6]Naþ 599.2647,
found 599.2689.
1
(CH2Cl2/CH3OH, 6:1); [a]D þ91.4 (c 0.7, CH3OH); H
NMR (500 MHz, D2O, dH) 5.16 (d, 1H, J¼1.0 Hz), 5.08 (s,
1H), 4.96 (s, 1H), 4.19–4.16 (m, 1H), 4.05–4.01 (m, 2H),
3.96–3.92 (m, 3H), 3.89–3.86 (m, 1H), 3.79–3.76 (m, 4H),
3.68–3.63 (m, 3H), 3.47–3.45 (m, 1H), 3.40 (s, 3H), 3.40
(s, 3H), 1.56–1.50 (m, 2H), 1.14–1.11 (m, 10H), 0.86–0.81
(m, 3H); 13C NMR (125 MHz, CDCl3, dC) 108.6, 105.5,
105.3, 91.6, 90.5, 86.4, 85.4, 82.9, 81.9, 80.2, 76.2, 75.2,
68.2, 66.3, 65.7, 63.3, 58.2, 58.0, 32.3, 29.9, 29.8, 29.7,
26.1, 23.1, 14.6; HR-ESI-MS calcd for [C25H46O13]Naþ
577.2831, found 577.2814.
4.1.7. Octyl 5-O-(2-amino-2-deoxy-a-D-arabinofurano-
syl)-a-D-arabinofuranoside (15). A solution of 12 (25 mg,
0.06 mmol) and triphenylphosphine (24 mg, 0.09 mmol) in
THF (5 mL) and few drops of water was stirred for 24 h at rt.
The solvent was concentrated and the residue purified by
chromatography (CHCl3/CH3OH, 2:1 with 2% Et3N) to
give 15 (15 mg, 70%) as a white solid: Rf 0.14 (CHCl3/
CH3OH, 2:1); [a]D þ91.2 (c 0.8, CH3OH); 1H NMR
(400 MHz, D2O, d) 5.09 (d, 1H, J¼1.8 Hz), 4.98 (s, 1H),
4.20–4.16 (m, 2H), 4.14–4.09 (m, 1H), 4.04 (dd, 1H,
J¼5.4, 11.6 Hz), 3.98–3.94 (m, 2H), 3.89–3.85 (m, 2H),
3.58–3.48 (m, 3H), 3.37–3.29 (m, 1H), 1.57–1.53 (m, 2H),
1.25–1.21 (m, 10H), 0.82–0.79 (m, 3H); 13C NMR
(100 MHz, D2O, d) 13C NMR (100 MHz, D2O, dC) 108.2,
105.7, 84.8, 81.2, 80.8, 79.7, 75.5, 72.0, 68.7, 62.0, 60.0,
59.7, 31.5, 29.0, 28.7, 25.6, 22.4, 13.8; HR-ESI-MS calcd
for [C18H35O8N]Naþ 416.2255, found 416.2259.
4.1.4. Octyl 5-O-(2-azido-2-deoxy-a-D-arabinofurano-
A solution of 27
syl)-a-D-arabinofuranoside (12).
(45 mg, 0.12 mmol), NaN3 (150 mg, 2.16 mmol) and
NH4Cl (140 mg, 2.45 mmol) in ethanol (15 mL) and water
(10 mL) was heated at reflux for 24 h. The reaction mixture
was cooled, concentrated, and the residue was purified by
chromatography (CH2Cl2/CH3OH, 10:1) to give 12 (30 mg,
60%) as a colorless oil: Rf 0.38 (CH2Cl2/CH3OH, 10:1);
1
[a]D þ84.3 (c 0.8, CH3OH); H NMR (400 MHz, CDCl3,
dH) 5.08 (d, 1H, J¼2.1 Hz), 4.98 (s, 1H), 4.18–4.16 (m,
2H), 4.10–4.08 (m, 1H), 4.05 (s, 1H), 3.98–3.95 (m, 2H),
3.91–3.86 (m, 2H), 3.77–3.70 (m, 3H), 3.46–3.41 (m, 1H),
1.61–1.59 (m, 2H), 1.25–1.23 (m, 10H), 0.89–0.86 (m,
3H); 13C NMR (100 MHz, CDCl3, dC) 108.6, 105.0, 85.4,
83.1, 81.8, 79.6, 75.2, 71.1, 68.4, 65.5, 61.9, 32.0, 29.7,
29.5, 29.4, 26.3, 22.8, 14.3; HR-ESI-MS calcd for
[C18H33O8N3]Naþ 442.2160, found 442.2168.
4.1.8. Octyl 3-O-(2-amino-2-deoxy-a-D-arabinofurano-
syl)-a-D-arabinofuranoside (16). Azide 13 (20 mg,
0.05 mmol) was converted to 16 as described for the
preparation of 15 with triphenylphosphine (24 mg,
0.09 mmol) in THF (5 mL) and few drops of water.
Purification of the product by chromatography (CHCl3/
CH3OH, 2:1 with 2% Et3N) gave 16 (10 mg, 63%) as a
white solid: Rf 0.14 (CHCl3/CH3OH, 2:1); [a]D þ83.2 (c
1
0.7, CH3OH); H NMR (400 MHz, D2O, dH) 5.07 (d, 1H,
4.1.5. Octyl 3-O-(2-azido-2-deoxy-a-D-arabinofurano-
syl)-a-D-arabinofuranoside (13). Epoxide 28 (30 mg,
0.08 mmol) was treated as described for the preparation of
12 with NaN3 (140 mg, 2.15 mmol) and NH4Cl (130 mg,
2.43 mmol) in ethanol (15 mL) and water (10 mL). The
product was purified by chromatography (CH2Cl2/CH3OH,
10:1) to give 13 (18 mg, 54%) as a colorless oil: Rf 0.42
J¼2.1 Hz), 4.84 (s, 1H), 4.06 (m, 1H), 4.05–3.96 (m, 4H),
3.87–3.78 (m, 3H), 3.73–3.64 (m, 2H), 3.44–3.38 (m, 1H),
3.01–2.99 (m, 1H),1.59–1.54 (m, 2H), 1.34–1.29 (m,
10H), 0.90–0.86 (m, 3H); 13C NMR (100 MHz, D2O, dC)
108.2, 105.0, 84.5, 83.7, 82.5, 82.6, 69.2, 68.4, 64.0, 60.6,
59.1, 31.9, 29.6, 29.4, 29.3, 26.1, 22.6, 14.1; HR-ESI-MS
calcd for [C18H35O8N]Naþ 416.2255, found 416.2252.
1
(CH2Cl2/CH3OH, 10:1); [a]D þ81.3 (c 0.8, CH3OH); H
NMR (400 MHz, CDCl3, dH) 5.17 (d, 1H, J¼1.9 Hz), 4.94
(s, 1H), 4.16 (s, 1H), 4.11 (m, 1H), 4.05–3.96 (m, 3H),
3.87–3.78 (m, 5H), 3.73–3.64 (m, 1H), 3.44–3.38 (m, 1H),
4.1.9. Octyl 3,5-di-O-(2-amino-2-deoxy-a-D-arabino-
furanosyl)-a-D-arabinofuranoside (17). Azide 14
(15 mg, 0.03 mmol) was converted to 17 as described for

O. M. Cociorva, T. L. Lowary / Tetrahedron 60 (2004) 1481–1489
1487
the preparation of 16 with triphenylphosphine (17 mg,
0.05 mmol) in THF (5 mL) and few drops of water.
Purification of the product by chromatography (CHCl3/
CH3OH, 2:1 with 2% Et3N) gave 17 (11 mg, 81%) as a
white solid: Rf 0.12 (CHCl3/CH3OH, 2:1); [a]D þ106.7 (c
isopropyldisiloxane (890 mg, 2.8 mmol) dropwise. The
reaction mixture was warmed at rt and stirred for 12 h
before benzoyl chloride (0.12 mL, 1.14 mmol) was added
dropwise. The reaction mixture was stirred at rt overnight,
then diluted with CH2Cl2 (25 mL) and washed successively
with 0.1 M HCl (50 mL), water (25 mL), and brine (25 mL).
After drying (Na2SO4), the solution was filtered, concen-
trated, and the residue was purified by chromatography
(hexanes/EtOAc, 6:1) to give 21 (1.07 g, 89%) as a colorless
oil: Rf 0.7 (hexanes/EtOAc, 6:1); [a]D 232.6 (c 2.1,
1
0.7, CH3OH); H NMR (400 MHz, D2O, dH) 5.10 (d, 1H,
J¼1.8 Hz), 5.07 (d, 1H, J¼2.1 Hz), 4.89 (s, 1H), 4.19–4.16
(m, 1H), 4.17–4.15 (m, 1H), 4.01–3.98 (m, 1H), 3.94–3.93
(m, 3H), 3.89–3.84 (m, 2H), 3.81–3.77 (m, 3H), 3.72–3.67
(m, 3H), 3.55–3.49 (m, 1H), 3.07–3.03 (m, 2H),1.56–1.52
(m, 2H), 1.26–1.17 (m, 10H), 0.82–0.79 (m, 3H); 13C NMR
(100 MHz, D2O, dC) 107.9, 107.8, 107.7, 85.7, 85.2, 84.0,
82.2, 81.8, 81.4, 79.4, 68.4, 66.6, 62.1, 62.0, 59.6 (2), 31.5,
29.0, 28.8, 28.6, 25.6, 22.4, 13.8; HR-ESI-MS calcd for
[C23H44O11N2]Naþ 547.2837, found 547.2836.
1
CHCl3); H NMR (400 MHz, CDCl3, dH) 8.06–8.03 (m,
2H), 7.59–7.57 (m, 1H), 7.45–7.43 (m, 2H), 5.43 (dd, 1H,
J¼1.5, 4.7 Hz), 5.00 (d, 1H, J¼1.5 Hz), 4.50 (dd, 1H,
J¼2.3, 5.1 Hz), 4.11–4.06 (m, 2H), 4.01–3.97 (m, 1H),
3.74–3.68 (m, 1H), 3.58–3.43 (m, 1H), 1.63–1.58 (m, 2H),
1.28–1.26 (m, 10H), 1.15–0.98 (m, 28H), 0.88–0.86 (m,
3H); 13C NMR (100 MHz, CDCl3, dC) 165.8, 133.4, 129.9,
129.8, 128.6 (2), 105.5, 84.7, 81.5, 76.7, 68.2, 62.3, 32.1,
29.8, 29.6, 29.5, 26.3, 22.9, 17.7, 17.6 (3), 17.2 (3), 14.3,
13.7, 13.5, 13.1, 12.8; HR-ESI-MS calcd for [C32H56O7-
Si2]Naþ 631.3457, found 631.3470.
4.1.10. Octyl 2,3-di-O-benzoyl-5-O-triphenylmethyl-a-D-
arabinofuranoside (19). To a solution of 1811 (500 mg,
1.91 mmol) in dry pyridine (10 mL) and dry CH2Cl2 (3 mL)
was added dropwise triphenylmethyl chloride (837 mg,
3.0 mmol) and DMAP (90 mg, 0.7 mmol). The reaction
mixture was stirred at rt overnight before benzoyl chloride
(1.5 mL, 11 mmol) was added dropwise. The solution was
again stirred at rt overnight, then diluted with CH2Cl2
(20 mL) and washed successively with 0.1 M HCl (30 mL),
water (15 mL), and brine (15 mL). After drying (Na2SO4),
the solution was filtered and concentrated to give 19 (1.2 g,
97%) as a light yellow oil: Rf 0.53 (hexanes/EtOAc, 4:1);
[a]D þ81.9 (c 0.9, CHCl3); 1H NMR (400 MHz, CDCl3, dH)
8.21–8.19 (m, 7H), 8.12–8.09 (m, 3H), 8.02–8.00 (m, 2H),
7.72–7.44 (m, 7H), 7.37–7.33 (m, 2H), 7.30–7.12 (m, 3H),
5.61 (d, 1H, J¼1.9 Hz), 5.48 (s, 1H), 5.28 (s, 1H), 4.49 (dd,
1H, J¼4.9, 9.9 Hz), 3.97 (s, 1H), 3.86–3.77 (m, 1H), 3.61–
3.50 (m, 2H), 3.12 (s, 1H), 1.73–1.68 (m, 2H), 1.48–1.32
(m, 10H), 0.94–0.86 (m, 3H); 13C NMR (100 MHz, CDCl3,
dC) 166.0, 165.8, 144.2, 135.0, 134.2, 133.7, 131.0, 130.6,
130.3, 130.0, 129.8, 129.3, 129.2, 128.9 (2), 128.8, 128.2
(2), 127.4, 127.3, 106.2, 87.3, 82.4, 78.4, 68.0, 64.1, 32.3,
30.0, 29.9, 29.7, 26.6, 23.1, 14.5; HR-ESI-MS calcd for
[C46H48O7]Naþ 735.3292, found 735.3303.
4.1.13. Octyl 2-O-benzoyl-a-D-arabinofuranoside (22).
To a solution of 21 (375 mg, 0.62 mmol) in dry THF
(15 mL) was added a solution of 1 M n-Bu4NF in THF
(1.55 mL, 1.55 mmol). The reaction mixture was stirred at rt
for 2 h and then CH2Cl2 (50 mL) and a saturated aqueous
solution of NaHCO3 (40 mL) were added. The organic layer
was dried (Na2SO4) then filtered and concentrated. The
residue was purified by chromatography (hexanes/EtOAc,
3:1) to give 22 (209 mg, 92%) as colorless oil: Rf 0.42
1
(hexanes/EtOAc, 1:1); [a]D 89.7 (c 0.9, CHCl3); H NMR
(400 MHz, CDCl3, dH) 8.03–8.01 (m, 2H), 7.61–7.58 (m,
1H), 7.47–7.44 (m, 2H), 5.25 (s, 1H), 5.08 (d, 1H,
J¼2.1 Hz), 4.22–4.15 (m, 2H), 3.95–3.92 (m, 1H), 3.80–
3.74 (m, 1H), 3.51–3.45 (m, 1H), 3.26 (d, 1H, J¼5.3 Hz),
1.63–1.61 (m, 2H), 1.34–1.27 (m, 10H), 0.89–0.87 (m,
3H); 13C NMR (100 MHz, CDCl3, dC) 167.1, 134.0, 130.2,
129.5, 128.9, 105.7, 86.4, 84.5, 76.8, 68.4, 62.4, 32.2, 29.9,
29.8, 29.6, 26.5, 23.0, 14.5; HR-ESI-MS calcd for
[C20H30O6]Naþ 389.1935, found 389.1935.
4.1.11. Octyl 2,3-di-O-benzoyl-a-D-arabinofuranoside
(20). To a solution of 19 (2.9 g, 4.07 mmol) in CH2Cl2/
CH3OH (20 mL, 3:1) was added p-TsOH acid (362 mg,
1.9 mmol) at rt and the mixture was stirred for 12 h, before
Et3N (0.1 mL) was added. The solution concentrated and the
residue was purified by chromatography (hexanes/EtOAc,
6:1) to give 20 (1.8 g, 94%) as a colorless oil: Rf 0.51
(hexanes/EtOAc, 2:1); [a]D þ91.5 (c 0.7, CHCl3); 1H NMR
(400 MHz, CDCl3, dH) 8.09–8.04 (m, 4H), 7.61–7.56 (m,
2H), 7.47–7.43 (m, 4H), 5.52 (d, 1H, J¼1.3 Hz), 5.42 (dd,
1H, J¼0.7, 4.7 Hz), 5.23 (s, 1H), 4.33–4.29 (m, 1H), 4.04–
3.95 (m, 2H), 3.78–3.73 (m, 1H), 3.55–3.49 (m, 1H), 1.66–
1.59 (m, 2H), 1.41–1.23 (m, 10H), 0.87–0.84 (m, 3H); 13C
NMR (100 MHz, CDCl3, dC) 166.6, 165.8, 133.9, 130.3 (2),
129.7, 129.6, 128.9 (2), 105.9, 84.0, 82.2, 78.3, 68.0, 62.9,
32.2, 30.0, 29.8, 29.7, 26.6, 23.0, 14.5; HR-ESI-MS calcd
for [C27H34O7]Naþ 493.2197, found 493.2189.
4.1.14. Octyl 2,5-di-O-benzoyl-a-D-arabinofuranoside
(23). To a solution of 22 (143 mg, 0.39 mmol) in dry THF
(5 mL), was added Ph3P (152 mg, 0.58 mmol) and the
mixture was stirred at rt for 15 min. Then, DEAD (0.1 mL,
0.58 mmol) and benzoic acid (71 mg, 0.58 mmol) were
added. After 1 h, the reaction mixture was concentrated a
syrup before ether (25 mL) was added to precipitate the
triphenylphosphine oxide. The two-phase mixture was kept
at 4 8C overnight then filtered and the precipitate washed
with cold ether. The filtrate was concentrated and, after
repeating the precipitation, purified by chromatography
(hexanes/EtOAc, 8:1) to give 23 (171 mg, 93%) as a white
solid: Rf 0.28 (hexanes/EtOAc, 8:1); [a]D þ78.9 (c 0.8,
1
CHCl3); H NMR (400 MHz, CDCl3, dH) 8.05–8.01 (m,
4H), 7.61–7.57 (m, 1H), 7.54–7.50 (m, 1H), 7.46–7.42 (m,
2H), 7.37–7.33 (m, 2H), 5.29 (s, 1H), 5.16 (d, 1H,
J¼1.8 Hz), 4.64 (dd, 1H, J¼4.0, 11.8 Hz), 4.55–4.51 (m,
1H), 4.47–4.44 (m, 1H), 4.25–4.23 (m, 1H), 3.84–3.78 (m,
1H), 3.55–3.49 (m 1H), 3.44 (d, 1H, J¼5.9 Hz), 1.66–1.61
(m, 2H), 1.39–1.28 (m, 10H), 0.90–0.87 (m, 3H); 13C NMR
(100 MHz, CDCl3, dC) 166.7, 166.5, 133.8, 133.2, 130.0 (2),
4.1.12. Octyl 2-O-benzoyl-3,5-O-(1,1,3,3-tetraisopropyl-
siloxane-1,3-diyl)-a-D-arabinofuranoside (21). To
a
solution of 1811 (500 mg, 1.90 mmol) in dry pyridine
(40 mL), at 0 8C, was added 1,3-dichloro-1,1,3,3-tetra-

1488
O. M. Cociorva, T. L. Lowary / Tetrahedron 60 (2004) 1481–1489
129.9, 129.2, 128.7, 128.5, 105.5, 85.6, 82.1, 77.5, 68.2,
64.1, 32.0, 29.7, 29.5, 29.4, 26.2, 22.8, 14.2; HR-ESI-MS
calcd for [C27H34O7]Naþ 493.2197, found 493.2208.
described for the synthesis of 24 using N-iodosuccinimide
(153 mg, 0.68 mmol) and silver triflate (44 mg, 0.17 mmol).
Purification of the product by chromatography (hexanes/
EtOAc, 4:1) gave 26 (165 mg, 75%) as a colorless oil: Rf
1
4.1.15. Octyl 5-O-(2,3-anhydro-5-O-benzoyl-a-D-ribo-
furanosyl)-2,3-di-O-benzoyl-a-D-arabinofuranoside
(24). A solution of acceptor 20 (92 mg, 0.19 mmol), donor
67b (80 mg, 0.23 mmol) and powdered molecular sieves
0.14 (hexanes/EtOAc, 2:1); [a]D þ91.2 (c 0.8, CHCl3); H
NMR (400 MHz, CDCl3, dH) 8.00–7.90 (m, 6H), 7.60–7.52
(m, 3H), 7.46–7.38 (m, 6H), 5.58 (s, 1H), 5.45 (s, 1H), 5.33
(s, 1H), 5.15 (s, 1H), 4.53–4.52 (m, 2H), 4.46 (dd, 2H,
J¼2.9, 12.1 Hz), 4.39–4.28 (m, 4H), 4.12 (dd, 1H, J¼4.1,
11.7 Hz), 4.02–3.99 (m, 1H), 3.91 (d, 1H, J¼2.3 Hz), 3.75–
3.69 (m, 4H), 3.47–3.42 (m, 1H), 1.62–1.58 (m, 2H), 1.33–
1.27 (m, 10H), 0.89–0.86 (m, 3H); 13C NMR (100 MHz,
CDCl3, dC) 166.5, 166.4, 166.0, 133.8, 133.7, 130.2, 130.1,
130.0, 129.9, 129.8, 129.0, 128.4, 106.1, 102.4, 102.2, 83.7,
83.5, 82.1, 76.6, 76.4, 68.0, 67.7, 65.1, 65.0, 56.5 (2), 56.2
˚
(4 A, 150 mg) in dry CH2Cl2 (10 mL) was stirred at 240 8C
for 10 min. Then, N-iodosuccinimide (52 mg, 0.23 mmol)
and silver triflate (10 mg, 0.04 mmol) were added. After
stirring for 10 min at 240 8C, Et3N (0.1 mL) was added.
The reaction mixture was then diluted with CH2Cl2 (10 mL)
and filtered through Celite. The filtrate was washed
successively with a saturated aqueous solution of Na2S2O3
(15 mL), water (15 mL), and brine (15 mL). After drying
(Na2SO4), the organic phase was filtered and concentrated.
The residue was purified by chromatography (hexanes/
EtOAc, 3:1) to give 24 (110 mg, 84%) as a colorless oil: Rf
0.51 (hexanes/EtOAc, 2:1); [a]D þ89.1 (c 0.7, CHCl3); 1H
NMR (400 MHz, CDCl3, dH) 8.11–8.05 (m, 4H), 8.00–7.98
(m, 2H) 7.60–7.53 (m, 3H), 7.46–7.40 (m, 6H), 5.52 (d, 1H,
J¼4.7 Hz), 5.47 (s, 1H), 5.45 (d, 1H, J¼1.0 Hz), 5.23 (s,
1H), 4.58 (dd, 1H, J¼3.9, 3.9 Hz), 4.48 (dd, 1H, J¼3.2,
12.0 Hz), 4.46–4.38 (m, 2H), 4.20 (dd, 1H, J¼4.9,
11.1 Hz), 4.07 (dd, 1H, J¼3.7, 11.1 Hz), 3.80–3.73 (m,
3H), 3.54–3.48 (m, 1H), 1.65–1.58 (m, 2H), 1.47–1.24 (m,
10H), 0.88–0.84 (m, 3H); 13C NMR (100 MHz, CDCl3, dC)
166.5, 166.1, 165.9, 133.8, 133.7, 130.4, 130.3, 130.0,
129.9, 129.7, 129.0, 128.8, 128.8, 106.1, 102.3, 82.5, 82.2,
78.3, 76.5, 68.4, 67.9, 65.1, 56.3, 56.2, 32.2, 30.0, 29.8,
29.7, 26.6, 23.1, 14.5; 1JC1,H1¼167.2 Hz; HR-ESI-MS calcd
for [C39H44O11]Naþ 711.2776, found 711.2718.
1
(2), 32.2, 29.8, 29.8, 29.6, 26.4, 23.1, 14.5; JC1,H1¼168.4,
167.9; HR-ESI-MS calcd for [C44H50O14]Naþ 825.3093,
found 825.3161.
4.1.18. Octyl 5-O-(2,3-anhydro-a-D-ribofuranosyl)-a-D-
arabinofuranoside (27). To a solution of 24 (90 mg,
0.13 mmol) in dry CH3OH (10 mL), was added a 0.1 M
solution of NaOCH3 in CH3OH until the pH of the solution
was 11. The reaction mixture was stirred at rt overnight and
then neutralized with few drops of acetic acid. The solution
was concentrated and the residue was purified by chroma-
tography (CH2Cl2/CH3OH, 8:1) to give 27 (45 mg, 92%) as
a colorless oil: Rf 0.65 (CH2Cl2/CH3OH, 6:1); [a]D þ97.6 (c
0.7, CH3OH); 1H NMR (400 MHz, CDCl3, dH) 5.34 (s, 1H),
5.01 (s, 1H), 4.35 (dd, 1H, J¼3.8, 3.8 Hz), 4.19 (d, 1H,
J¼2.1 Hz), 4.05 (d, 1H, J¼10.5 Hz), 4.00–3.96 (m, 1H),
3.89 (dd, 1H, J¼2.5, 10.7 Hz), 3.85–3.83 (m, 2H), 3.75–
3.64 (m, 3H), 3.46–3.40 (m, 1H), 3.11 (d, 1H, J¼10.8 Hz),
1.58–1.55 (m, 2H), 1.28–1.27 (m, 10H), 0.89–0.86 (m,
3H); 13C NMR (100 MHz, CDCl3, dC) 108.7, 101.7, 86.3,
79.9, 79.7, 78.7, 68.4, 68.1, 63.3, 58.0, 57.1, 32.2, 29.9,
29.7, 29.6, 26.5, 23.0, 14.5; HR-ESI-MS calcd for
[C18H32O8]Naþ 399.1989, found 399.2004.
4.1.16. Octyl 3-O-(2,3-anhydro-5-O-benzoyl-a-D-ribo-
furanosyl)-2,5-di-O-benzoyl-a-D-arabinofuranoside
(25). Disaccharide 25 was prepared from 23 (47 mg,
0.1 mmol) and 67b (40 mg, 0.12 mmol) and powdered
˚
molecular sieves (4 A, 100 mg) in dry CH2Cl2 (10 mL) as
described for the synthesis of 24 using N-iodosuccinimide
(27 mg, 0.12 mmol) and silver triflate (10 mg, 0.04 mmol).
Purification of the product by chromatography (hexanes/
EtOAc, 4:1) gave 25 (130 mg, 89%) as a colorless oil: Rf
0.19 (hexanes/EtOAc, 2:1); [a]D þ97.6 (c 0.8, CHCl3); 1H
NMR (400 MHz, CDCl3, dH) 8.05–7.96 (m, 6H), 7.59–7.55
(m, 2H), 7.49–7.37 (m, 5H), 7.27–7.23 (m, 2H), 5.66 (s,
1H), 5.35 (d, 1H, J¼1.3 Hz), 5.23 (s, 1H), 4.72 (dd, 1H,
J¼2.8, 11.4 Hz), 4.60–4.51 (m, 3H), 4.44 (dd, 1H, J¼3.2,
11.6 Hz), 4.37 (d, 1H, J¼5.7 Hz), 4.29 (dd, 1H, J¼4.2,
12.0 Hz), 3.93 (dd, 1H, J¼0.4, 2.7 Hz), 3.79–3.73 (m, 2H),
3.53–3.47 (m, 1H), 1.66–1.60 (m, 2H), 1.38–1.27 (m,
10H), 0.89–0.86 (m, 3H); 13C NMR (100 MHz, CDCl3, dC)
166.7, 166.5, 166.0, 133.9, 133.7, 133.4, 130.3, 130.2, 130.1
(2), 129.9, 129.8, 129.0, 128.9, 128.7, 106.1, 102.0, 83.9,
83.8, 80.8, 76.8, 68.1, 65.0, 63.8, 56.6 (2), 32.3, 29.8 (2),
29.6, 26.5, 23.1, 14.5; 1JC1,H1¼166.9 Hz; HR-ESI-MS calcd
for [C39H44O11]Naþ 711.2776, found 711.2723.
4.1.19. Octyl 3-O-(2,3-anhydro-a-D-ribofuranosyl)-a-D-
arabinofuranoside (28). Disaccharide 25 (130 mg,
0.19 mmol) dissolved in dry CH3OH (20 mL) was
debenzoylated with a 0.1 M solution of NaOCH3 in
CH3OH as described for the synthesis of 27. The product
was purified by chromatography (CH2Cl2/CH3OH, 10:1) to
give 28 (70 mg, 98%) as a colorless oil: Rf 0.67 (CH2Cl2/
CH3OH, 6:1); [a]D þ100.2 (c 0.6, CH3OH); 1H NMR
(400 MHz, CDCl3, dH) 5.51 (s, 1H), 4.92 (s, 1H), 4.32 (m,
1H), 4.20–4.10 (m, 3H), 3.86–3.85 (m, 3H), 3.75 (m, 1H),
3.68 (d, 1H, J¼2.7 Hz), 3.67–3.63 (m, 2H), 3.41–3.38 (m,
1H), 1.59–1.55 (m, 2H), 1.28–1.27 (m, 10H), 0.89–0.86
(m, 3H); 13C NMR (100 MHz, CDCl3, dC) 108.1, 101.9,
84.0, 82.3, 81.1, 79.8, 68.2, 63.1, 61.0, 56.8 (2), 32.2, 29.9,
29.8, 29.7, 26.5, 23.0, 14.5; HR-ESI-MS calcd for
C18H32O8]Naþ 399.1989, found 399.1980.
4.1.20. Octyl 3,5-di-O-(2,3-anhydro-a-D-ribofuranosyl)-
a-D-arabinofuranoside (29). Trisaccharide 26 (70 mg,
0.08 mmol) dissolved in dry CH3OH (10 mL) was
debenzoylated with a 0.1 M solution of NaOCH3 in
CH3OH as described for the synthesis of 27. The product
was purified by chromatography (CH2Cl2/CH3OH, 6:1) to
give 29 (35 mg, 89%) as a colorless oil: Rf 0.60 (CH2Cl2/
4.1.17. Octyl 3,5-di-O-(2,3-anhydro-5-O-benzoyl-a-D-
ribofuranosyl)-2-O-benzoyl-a-D-arabinofuranoside
(26). Trisaccharide 26 was prepared from 22 (100 mg,
0.27 mmol) and 67b (233 mg, 0.68 mmol) and powdered
˚
molecular sieves (4 A, 100 mg) in dry CH2Cl2 (15 mL) as

O. M. Cociorva, T. L. Lowary / Tetrahedron 60 (2004) 1481–1489
1489
CH3OH, 6:1); [a]D þ68.9 (c 1.0, CH3OH); 1H NMR
(400 MHz, CDCl3, dH) 5.46 (s, 1H), 5.37 (s, 1H), 4.95 (s,
1H), 4.34–4.31 (m, 2H), 4.22–4.17 (m, 3H), 4.11–4.08 (m,
1H), 3.91–3.85 (m, 3H), 3.75–3.62 (m, 6H), 3.43–3.37 (m,
1H), 1.58–1.55 (m, 2H), 1.28–1.26 (m, 10H), 0.89–0.86
(m, 3H); 13C NMR (100 MHz, CDCl3, dC) 108.4, 102.4,
102.0, 84.7, 81.8, 80.8, 79.8, 79.6, 68.3 (2), 63.2 (2), 57.5,
57.1, 56.7 (2), 32.2, 29.9, 29.8, 29.7, 26.4, 23.1, 14.5; HR-
ESI-MS calcd for [C23H38O11]Naþ 513.2306, found
513.2289.
5. (a) Boons, G.-J. Glycosides as donors. In Glycoscience:
chemistry and chemical biology; Fraser-Reid, B., Tatsuta, K.,
Thiem, J., Eds.; Springer: Berlin, 2001; pp 551–581. (b) Davis,
B. G. J. Chem. Soc., Perkin Trans. 1 2000, 2137. (c) Ley, S. V.;
Priepke, H. W. M. Angew. Chem. Intl. Ed. Engl. 1994, 33,
2292. (d) Fraser-Reid, B.; Wu, Z.; Andrews, C. W.;
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Acknowledgements
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This work was supported by The National Institutes of
Health (AI44045-01). We thank Christopher S. Callam and
Jeong-Seok Han for technical assistance.
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