Probing the effect of acylation on arabinofuranose ring conformation in di- and trisaccharide fragments of mycobacterial arabinogalactan

Article abstract of DOI:10.1021/jo100575a

(Figure presented) A major component of the cell wall of mycobacteria is the mycolyl-arabinogalactan (mAG) complex. The arabinose and galactose residues in mAG are found solely in the furanose form, and it has been suggested that the flexibility of these five-membered rings allows for the tight packing of mycolic acids. In order to probe the flexible scaffold hypothesis , we designed and synthesized glycolipids 3-6 and 8-11 as simple models of the terminal portion of mAG. A set of donors and acceptors were explored for preparing the key β-(1→2) linkage in 2-6, and the best selectivity and yield can be obtained by using the electron-rich thioglycoside donor 14 and the O-5 p-methoxybenzyl-protected acceptor 17. Both α-linkages in the trisaccharides 7-11 were formed in a one-pot reaction. The conformations of compounds 2-11 were studied using solution-state NMR spectroscopy, but little change was observed in the coupling constants for the ring protons between 2 and 3-6 or between 7 and 8-11. However, the rotamer populations about the C-4-C-5 bond for the β-linked ring in disaccharide 2 did change upon acylation at O-5.

Full text of DOI:10.1021/jo100575a

pubs.acs.org/joc
Probing the Effect of Acylation on Arabinofuranose Ring Conformation in
Di- and Trisaccharide Fragments of Mycobacterial Arabinogalactan
Chunjuan Liu, Michele R. Richards, and Todd L. Lowary*
Alberta Ingenuity Centre for Carbohydrate Science and Department of Chemistry, The University of Alberta,
Gunning-Lemieux Chemistry Centre, Edmonton, Alberta, T6G 2G2 Canada
tlowary@ualberta.ca
Received March 25, 2010
A major component of the cell wall of mycobacteria is the mycolyl-arabinogalactan (mAG)
complex. The arabinose and galactose residues in mAG are found solely in the furanose form, and
it has been suggested that the flexibility of these five-membered rings allows for the tight packing of
mycolic acids. In order to probe the “flexible scaffold hypothesis”, we designed and synthesized
glycolipids 3-6 and 8-11 as simple models of the terminal portion of mAG. A set of donors and
acceptors were explored for preparing the key β-(1f2) linkage in 2-6, and the best selectivity and
yield can be obtained by using the electron-rich thioglycoside donor 14 and the O-5 p-methoxybenzyl-
protected acceptor 17. Both R-linkages in the trisaccharides 7-11 were formed in a one-pot reaction.
The conformations of compounds 2-11 were studied using solution-state NMR spectroscopy, but
little change was observed in the coupling constants for the ring protons between 2 and 3-6 or
between 7 and 8-11. However, the rotamer populations about the C-4-C-5 bond for the β-linked
ring in disaccharide 2 did change upon acylation at O-5.
Introduction
located outside of the plasma membrane,3,4 and this bilayer
is made up of the unique mycolyl-arabinogalactan (mAG)
complex attached to peptidoglycan, as well as various lipids,
including trehalose mycolates, phospholipids, and phenolic
glycolipids.2 The mAG complex is essential for the viability
of M. tuberculosis;5 in fact, two of the front line drugs used to
treat tuberculosis inhibit the biosynthesis of mAG.6 The mAG
is linked to peptidoglycan through a phosphodiester bond
to a linker disaccharide of R-D-GlcpNAc-(1f3)-R-L-Rhap.7
Tuberculosis remains a major health concern worldwide,
with 9.3 million new cases and 1.8 million deaths in 2007.1
The disease is caused by the bacterium Mycobacterium
tuberculosis, which produces an unusual cell wall compared
to other Gram-positive bacteria.2 A second lipid bilayer is
(1) Global Tuberculosis Control 2009: Epidemiology, Strategy, Financing;
World Health Organization: Geneva, March 24, 2009.
(2) Bhamidi, S.; Scherman, M. S.; McNeil, M. R. Mycobacterial Cell
Wall Arabinogalactan: A Detailed Perspective on Structure, Biosynthesis,
Functions and Drug Targeting. In Bacterial Polysaccharides: Current Inno-
vations and Future Trends; Ullrich, M., Ed.; Caister Academic Press: Norfolk,
UK, 2009; pp 39-65.
(5) Pan, F.; Jackson, M.; Ma, Y. F.; McNeil, M. J. Bacteriol. 2001, 183,
3991–3998.
(6) Janin, Y. L. Bioorg. Med. Chem. 2007, 15, 2479–2513.
(7) Mahapatra, S.; Basu, J.; Brennan, P. J.; Crick, D. C. Structure,
Biosynthesis, and Genetics of the Mycolic Acid-Arabinogalactan-Peptido-
glycan Complex. In Tuberculosis and the Tubercle Bacillus; Cole, S. T.,
Eisenback, K. D., McMurray, D. N., Jacobs, W. R., Jr., Eds.; ASM Press:
Washington, D.C., 2005; pp 275-285.
(3) Zuber, B.; Chami, M.; Houssin, C.; Dubochet, J.; Griffiths, G.; Daffe,
M. J. Bacteriol. 2008, 190, 5672–5680.
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4992 J. Org. Chem. 2010, 75, 4992–5007
Published on Web 07/14/2010
DOI: 10.1021/jo100575a
r
2010 American Chemical Society

Liu et al.
JOCArticle
FIGURE 1. (Left) Hexasaccharide motif, 1, found at the nonreducing end of mycobacterial arabinogalactan (AG). (Right) Three represen-
tative examples of mycolic acids found in M. tuberculosis.
A linear chain of 30 galactofuranose with alternating β-(1f5)
and β-(1f6) linkages is attached to this disaccharide, and at
residues 8, 10, and 12 are attached arabinan chains.8 These
arabinose moieties are also in the furanose form, and the
31 monosaccharide residues are linked in a combination of
R-(1f5), R-(1f3), and β-(1f2) linkages.7,9,10 The arabinan
chain is capped at the nonreducing end with the branched
hexasaccharide shown in Figure 1 and esterified at O-5 of
residues C, D, E, and F with mycolic acids, which are R-alkyl,
β-hydroxy lipids with 60-90 carbon atoms.11,12
NMR spectroscopy. These relatively simple analogues were
chosen as the first targets as this provided us with the oppor-
tunity to develop the methodology that could be used to pre-
pare and study more complicated analogues that bear closer
resemblance to the natural polymeric glycolipid. Moreover,
such investigations were necessary in the interest of carrying
out a systematic study, in which a variety of structural fea-
tures (e.g., the size of the carbohydrate moiety and the length,
branching, and functionalization of the lipid portion) were to
be explored.
An interesting feature of the mAG complex is the presence
of only furanose sugars, aside from the pyranose residues of
the linker disaccharide. Their unusual configuration has led
to the proposal that the significant flexibility of the furanose
rings facilitates the tight packing of the mycolic acids, the
so-called “flexible scaffold hypothesis”.13,14 The tight packing
of these mycolic acids, in turn, provides a dense, low perme-
ability lipid barrier to the passage of antibiotics into the
organism, which facilitates its survival. This is an intriguing
hypothesis, but there is little experimental support for it. We
reasoned that one approach for testing the flexible scaffold
hypothesis would be to compare the conformation of the
furanose rings in fragments of mycobacterial arabinan with
analogues in which O-5 of the terminal residues had been
acylated with lipid chains of varying lengths. It could be
expected that, if this hypothesis is correct, conformational
differences between the acylated and unacylated compounds
would be observed. Thus, we describe here the synthesis of a
series of di- and trisaccharide glycolipids (Chart 1) and sub-
sequent conformational analysis of these compounds using
Results and Discussion
The first challenge to be faced was to select a method for
the synthesis of the disaccharide targets 2-6, which contain
a 1,2-cis-arabinofuranoside (β-arabinofuranoside) linkage.
A number of choices exist for the preparation of 1,2-cis-
arabinofuranosides. For example, previous work15,16 from
our group has led to the development of an indirect method
for preparing β-arabinofuranosides by employing 2,3-anhydro-
furanosyl donors, which stereroselectively give the β-glyco-
side. Another indirect method, the intramolecular aglycon
delivery approach, has also been reported to be effective for
the preparation of β-arabinofuranosides.17-21 A direct method
developed by Kim and co-workers22 relies on 2-carboxybenzyl
donors. Glycosylations with acceptors having benzoyl groups
or hindered secondary alcohols afforded excellent yields
of the β-glycosides, whereas benzyl-protected alcohols or
primary alcohols gave a mixture of R- and β-arabinofurano-
sides with no significant stereoselectivity. Recently, donors
(15) Gadikota, R. R.; Callam, C. S.; Lowary, T. L. Org. Lett. 2001, 3,
607–610.
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T. L. J. Am. Chem. Soc. 2003, 125, 4155–4165.
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P. G.; Morris, H. R.; Dell, A.; Sahm, H.; Eggeling, L.; Besra, G. S. J. Biol.
Chem. 2005, 280, 32362–32371.
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2007, 129, 9885–9901.
(10) Bhamidi, S.; Scherman, M. S.; Rithner, C. D.; Prenni, J. E.; Chatterjee,
D.; Khoo, K.-H.; McNeil, M. R. J. Biol. Chem. 2008, 283, 12992–13000.
(11) Bhowruth, V.; Alderwick, L. J.; Brown, A. K.; Bhatt, A.; Besra, G. S.
Biochem. Soc. Trans. 2008, 36, 555–565.
(12) Takayama, K.; Wang, C.; Besra, G. S. Clin. Microbiol. Rev. 2005, 18,
81–101.
(13) Nikaido, H.; Kim, S.-H.; Rosenberg, E. Y. Mol. Microbiol. 1993, 8,
1025–1030.
(14) Brennan, P. J.; Nikaido, H. Annu. Rev. Biochem. 1995, 64, 29–63.
659–660.
(19) Sanchez, S.; Bamhaoud, T.; Prandi, J. Tetrahedron Lett. 2000, 41,
7447–7452.
(20) Marotte, K.; Sanchez, S.; Bamhaoud, T.; Prandi, J. Eur. J. Org.
Chem. 2003, 3587–3598.
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4250–4263.
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2005, 7, 3263–3266.
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CHART 1. Target Di- and Trisaccharides (The Rings Have Been
Labeled To Facilitate Comparison with 1)
CHART 2. Donors (12-15) and Acceptors (16 and 17) Used in
β-Arabinofuranosylation Reactions
withdrawing protecting groups on O-5 can be envisioned.
We describe here the development and optimization of this
methodology with various donors (12-15) and acceptors
(16 and 17, Chart 2) and its application to the synthesis of
a panel of disaccharide targets. With this panel of com-
pounds, it was possible to probe the effect of the protecting
group on O-5 of the donor and acceptor on reaction stereo-
selectivity.
Preparation of Thioglycoside Donors 12-15. The thio-
glycoside donors 12 and 13 were synthesized according to
the literature.28-30 Donors 14 and 15 were synthesized
from known compound 1816,29 (Scheme 1). The free O-5
hydroxyl group in 18 was reacted with sodium hydride and
allyl bromide to give donor 14 in excellent (91%) yield.
Reaction of the same hydroxyl group with tert-butyldi-
methylsilyl chloride (TBDMSCl) and imidazole gave donor
15 in 75% yield.
Preparation of Acceptors 16 and 17. With the synthesis of
the donors finished, we explored the synthesis of acceptors
starting from methyl R-D-arabinofuranoside 19 (Scheme 2).
By employing Mitsunobu conditions,31 the epoxide ring was
introduced by reaction of 19 with diisopropyl azodicarboxy-
late (DIAD) and triphenylphosphine, which gave exclusively
the desired product 20 in 90% yield.
We optimized the method for the introduction of the
benzyl group at O-3, which involved opening of the epoxide
ring with sodium benzylate. The best results were obtained
when 20 was reacted with 2 equiv of sodium benzylate at high
concentration at 100 °C overnight. Under these conditions,
the reaction gave diol 21 in 80% yield. The regioselectivity
was confirmed by the proton chemical shift of the corres-
ponding acylated derivative of 21, which has a significant
downfield shift of H-2. By controlling the reaction tempera-
ture at -10 °C and the amount of benzoyl chloride, selective
protection of 21 at the primary position of the diol gave accep-
tor 16, which was obtained in 87% yield.
containing a cyclic protecting group have been used to in-
crease the β-stereoselectivity in the preparation of arabino-
furanosides. Boons and co-workers23-25 and later Crich24
and Zhu26,27 have used a di-tert-butyl silane (DTBS) acetal
to protect the O-3 and O-5 positions in a thioglycoside
donor. By rigidifying the flexible furanose ring, the resulting
oxocarbenium ion is locked in a conformation that shields
the R-face from attack. The β-face, on the other hand, is less
hindered; hence, the glycosylation gives excellent β-selecti-
vities with a range of acceptors having either primary or secon-
dary alcohols. In related work, Ito and co-workers28 used a
1,3-(1,1,3,3)-tetraisopropyldisiloxanylidene protecting group
to protect the O-3 and O-5 positions of a thioglycoside donor
to enhance the β-selectivity.
However, the need to install base-sensitive ester linkages
on both of the primary hydroxy groups in the disacchari-
des made many of these approaches impractical (e.g., the 2,3-
anhydrosugar method, or the use of 2-carboxybenzyl donors,
which provides high selectivity only when acylated acceptors
are used) or cumbersome (e.g., the use of DTBS-protected
donors, which would require a series of postglycosylation
protection-deprotection steps). Therefore, other approaches
were explored.
For the design of the donors, it is desirable to install a
group that can be readily removed in the presence of other
protecting groups because the O-5 position will be acylated
in the final products. In addition, O-2 should be protected
with nonparticipating benzyl ether, and to maximize the
reactivity of the donor, an electron-rich benzyl group should
also be used to protect O-3. With regard to the acceptor, the
O-3 position should be protected with benzyl ether as its
electron-donating nature will increase the nucleophilicity of
hydroxyl group at C-2, and O-5 should be protected with
groups that could be removed in the presence of benzyl
groups. Keeping in mind these criteria, a number of potential
donor and acceptor pairs with different electron-donating/
To synthesize acceptor 17, epoxide 20 was treated with
sodium hydride and p-methoxybenzyl chloride (PMBCl) to
afford the protected epoxide 22 in 80% yield. As before, ring
opening of the epoxide in 23 with sodium benzylate gave the
desired compound 17 in 77% yield.
Glycosylation of Donors 12-15 and Acceptors 16 and 17.
For determining optimal conditions to use in the glycosyla-
tions reactions, we studied the reaction of 13 and 16 (Table 1).
We first evaluated the effect of temperature (entries 1-5) using
(23) Zhu, X.; Kawatkar, S.; Rao, Y.; Boons, G.-J. J. Am. Chem. Soc.
2006, 128, 11948–11957.
(24) Rao, Y.; Boons, G.-J. Angew. Chem., Int. Ed. 2007, 46, 6148–6151.
(25) Rao, Y.; Buskas, T.; Albert, A.; O’Neill, M. A.; Hahn, M. G.; Boons,
G.-J. ChemBioChem 2008, 9, 381–388.
(26) Crich, D.; Pedersen, C. M.; Bowers, A. A.; Wink, D. J. J. Org. Chem.
2007, 72, 1553–1565.
(27) Wang, Y.; Maguire-Boyle, S.; Dere, R. T.; Zhu, X. Carbohydr. Res.
2008, 343, 3100–3106.
(28) Ishiwata, A.; Akao, H.; Ito, Y. Org. Lett. 2006, 8, 5525–5528.
(29) Ishiwata, A.; Akao, H.; Ito, Y.; Sunagawa, M.; Kusunose, N.;
Kashiwazaki, Y. Bioorg. Med. Chem. 2006, 14, 3049–3061.
(30) Yin, H.; Lowary, T. L. Tetrahedron Lett. 2001, 42, 5829–5832.
(31) Mitsunobu, O. Synthesis 1981, 1–28.
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SCHEME 1. Synthesis of Thioglycoside Donors 14 and 15
SCHEME 2. Synthesis of Acceptors 16 and 17
TABLE 1. Optimization of β-Arabinofuranosylation Using Thioglycoside 13 and Acceptor 16
entry
solvent
temperature
time (h)
acceptor concentration (M)
activator
yield (R/β)d
1
2
3
4
5
6
7
8
9
10
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
-78 °C f rt
4
6
4
0.5
1
1
1.5
2
0.5
6
0.08
0.08
0.08
0.08
0.08
1.00
0.05
0.01
0.01
0.01
b
NIS-AgOTfa
NIS-AgOTfa
NIS-AgOTfa
NIS-AgOTfa
NIS-AgOTfa
NIS-AgOTfa
NIS-AgOTfa
NIS-AgOTfa
NIS-TMSOTfb
Ph2SO-TTBP-Tf2Oc
81% (3.1:1)
85% (3:1)
91% (3.4:1)
74% (4.6:1)
89% (4.2:1)
84% (4.3:1)
85% (4:1)
93% (3:1)
78% (5:1)
63% (4:1)
-78 °C
-60 °C
-40 °C
-60 °C f -40 °C
-60 °C f -40 °C
-60 °C f -40 °C
-60 °C f -40 °C
-60 °C f -40 °C
-60 °C f -40 °C
aAcceptor 16 (1 equiv), donor 13 (1.2 equiv), NIS (1.2 equiv), AgOTf (0.1 equiv). Acceptor 16 (1 equiv), donor 13 (1.2 equiv), NIS (1.2 equiv),
TMSOTf (0.1 equiv). Acceptor 16 (1 equiv), donor 13 (1.2 equiv), Ph2SO (3 equiv), TTBP (6 equiv), Tf2O (1.1 equiv). dRatio was determined by
c
1H NMR spectroscopy.
the standard N-iodosuccinimide and silver trifluoromethane-
sulfonate (NIS-AgOTf) promoter system32 and dichloro-
methane as the solvent. When the glycosylations were carried out
at -78 °C, the reactions were very slow and usually took 5-6hto
finish. Performing the reaction -60 °C led to reduced reaction
times (3-4 h). We then found that at -40 °C the reaction pro-
ceeded very quickly but that the yield decreased. Thus, we deve-
loped an approach where the reaction was started at -60 °C and
then slowly warmed to -40 °C over 2 h. Under these condi-
tions, the reaction gave improved yield and stereoselectivity.
The effect of concentration was also studied (entries 6-8)
and was shown not to have a dramatic effect on the yield,
although at the lowest concentration investigated (0.01 M),
the β-selectivity was sowewhat increased. In addition, other
glycoslyaton promoters, such as NIS-trimethylsilyl trifluoro-
methanesulfonate (TMSOTf)33,34 and diphenyl sulfoxide, 2,4,6-
tri-tert-butylpyrimidine, and trifluoromethanesulfonic anhydride
(Ph2SO-TTBP-Tf2O),35 were investigated (entires 9 and 10).
However, with these promoters, the yield of the product was
reduced as was the β-selectivity. Finally, we studied the use of
acetonitrile, diethyl ether, toluene, and dioxane as the solvent.
€
€
(33) van Well, R. M.; Karkkainen, T. S.; Kartha, K. P. R.; Field, R. A.
Carbohydr. Res. 2006, 341, 1391–1397.
(34) Boons, G.-J.; Bowers, S.; Coe, D. M. Tetrahedron Lett. 1997, 38,
3773–3776.
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J. Org. Chem. Vol. 75, No. 15, 2010 4995

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SCHEME 3. Glycosylation of Donors 12-15 with Acceptors 16 and 17
TABLE 2. Glycosylation with Thioglycosides 12-15
donor 15 gave poor β-selectivity. One result that remained
unclear was why the more electron-rich, “armed” donors 12
and 14 gave better β-selectivity than the less electron-rich,
“disarmed” one, 13. Armed donors37 are more reactive; thus,
the glycosylation should proceed faster and prefer an oxocarbe-
nium ion intermediate resulting in the formation of R/β mix-
tures. However, in our case, the combination of the most active
donor 12 and acceptor 17 gave the best β/R ratio. This find-
ing is consistent with earlier work both from the Ito labo-
ratory28,29 as well as from our laboratory.38,39
entry
acceptor
donor
product
yield (%)
R/β ratioa
1
2
3
4
5
6
7
16
16
16
17
17
17
17
12
13
14
12
13
14
15
b
23
24
25
26
27
28
96
93
96
89
93
93
91
1:3
3:1
1:2.5
1:7.7
1:4.4
1:6.3
1:2
aRatio determined by weight of the isolated pure compounds. The
R/β ratio of products could not be separated; ratio was determined by
1H NMR spectroscopy.
b
Synthesis of Disaccharide Targets 2 and 30. Once the opti-
mization of the β-arabinofuranosyl reaction was complete,
we then synthesized the target disaccharides. As indicated in
Table 2, treatment of acceptor 17 with donor 12 yielded the
best R/β ratio, 1:7.7. However, the separation of the isomers
was difficult; therefore, the combination of acceptor 17 and
donor 14 was chosen to synthesize the disaccharides. Although
the reaction was a bit less stereoselective, 1:6.3 R/β, the
R- and β-isomers were easily separated after the removal of
the allyl group (Scheme 4). With a route to the pure β-isomer
29 in place, reaction with trifluoroacetic acid cleaved the
p-methoxybenzyl ether affording 30, which was ready for
acylation. Alternatively, hydrogenolysis of 29 with 20%
palladium hydroxide on carbon gave the fully deprotected
disaccharide 2 in 85% yield.
Preparation of Trisaccharides 7 and 34. In comparison with
the synthesis of the β-linked disaccharide, the target trisaccha-
rides had two R-glycosidic linkages, which can be readily con-
structed by the use of donors with participating acyl groups on
O-2. In designing the synthetic approach to the trisaccharides, we
chose an efficient and convergent route, in which the target was
assembled by the coupling of a diol acceptor and a single donor
to add both R-arabinofuranosyl residues in a single reaction.
With this consideration in mind, trisaccharide 7 was synthe-
sized according to the literature.40 Similarly, the O-5-depro-
tected trisaccharide 34 was assembled from known building
blocks 3140 and 3238 in a straightforward way by glycosylation
at 0°CusingNIS-AgOTfasthepromoter(Scheme5).Reaction
However, when performed in any of these solvents, the reactions
required extended reaction times and gave poor selectivity
compared to those carried out in dichloromethane.
The investigations described above allowed us to identify a set
of optimized conditions for coupling donors 12-15 with accep-
tors 16 and 17 (Scheme 3). All reactions were carried out at
an acceptor concentration of 0.01 M by cooling the donor
(1.2 equiv) and acceptor (1 equiv) in dichloromethane at -60 °C,
then NIS and AgOTf were added and the reaction was warmed to
-40 °C over 90-120 min. Following workup, the reaction mix-
ture was purified by chromatography, and the isolated anomeric
glycosides were characterized. Distinction between R- and β-
isomers was achieved by using δC-1 and 3JH-1,H-2 values.36 For the
3
β-isomer, δC-1 = 97-103 ppm, JH-1,H-2 = 3-5 Hz, whereas
for the R-isomer, δC-1 =104-111 ppm, 3JH-1,H-2 =0-2 Hz. As
Table 2 indicates, the yields of these reactions were very good
overall, but the R/βratios changed significantly, depending on the
different substituents on the donors and acceptors.
The treatment of the O-5 benzoyl-protected acceptor 16
with any of the donors gave poor to moderate β-selectivity.
However, when the p-methoxybenzyl-protected acceptor 17
was used, the β/R ratios were enhanced and moderate to good
β-selectivity was observed. In other words, the more electron-
rich acceptor favored the formation of the β-glycoside.
As expected, the structure of the donor also greatly influ-
enced the selectivity. For instance, the ester-protected donor
13 gave poor to moderate selectivity, whereas the two ether-
protected species (12 and 14) gave better β-selectivity; the
p-methoxybenzyl ether, 12, provides slightly more of the
β-anomer than the allyl ether, 14. Finally, the silyl-substituted
(37) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B.
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(38) Yin, H.; D’Souza, F. W.; Lowary, T. L. J. Org. Chem. 2002, 67,
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SCHEME 4. Synthesis of Disaccharides 2 and 30
SCHEME 5. Synthesis of Trisaccharide 34
of an excess donor 31 with diol 32 afforded the desired
trisaccharide 33 in 88% yield. Conversion of 33 to the target
diol 34 was carried out by subsequent removal of the benzoyl
groups, benzylation, and cleavage of the silyl ethers, in 74%
over three steps. Confirmation of the stereochemistry was
again possible by using 1H and 13C NMR spectroscopy. For
methanol, and a mixture of methanol and ethyl acetate, were
also tested. However, only the dichloromethane-methanol
system gave a good product yield in a reasonable reaction
time, usually overnight, at room temperature. Also, to avoid
the possible formation of micelles of the partially deprotec-
ted compounds, which we anticipated would slow the hetero-
geneous debenzylation reaction, the concentration of the
substrate was kept low, below 0.01 M.
NMR Analysis for the Measurement of Coupling Constants.
While compounds 2 and 7 are fully soluble in D2O, none of
the glycolipids 3-6 and 8-11 are, which limited the choice
of solvents available for conformational analysis. Thus, in all
experiments, NMR spectra were acquired using a solution of
the target compound in CD3OD or 1:1 CDCl3-CD3OD. As
outlined below, the choice of solvent had negligible effect
on conformation and, in turn, coupling constant values. The
assignment process is summarized below.
For the assignment of resonances in the spectra of the oligo-
saccharides, we followed the “structural reporter group”
concept developed by Vliegenthart and co-workers.41 The
R- and β-arabinofuranosides have distinct and well-resolved
signals in this region of the spectrum, and the stereochemistry
of glycosidic linkages can be determined from their 3JH-1,H-2
values, as described above. These proton resonances are
correlated with carbon signals (110-90 ppm) by using 2D
HMQC or HSQC experiments. The remainder of the ring
protons were assigned by means of 2D COSY and TOCSY
experiments. In addition, all of the 1D 1H NMR spectra were
simulated using the program WinDNMR42 to extract accurate
1
instance, in 34, the three anomeric signals in the H NMR
spectrum, 5.17 ppm (singlet), 5.13 ppm (doublet, J=1.5 Hz),
4.96 ppm (doublet, JH-1,H-2=1.5 Hz), indicated the presence
of three R-arabinofuranosyl linkages. In the 13C NMR spec-
trum of 34, these signals are correlated to resonances at
106.9, 106.2, and 105.9 ppm, respectively, by HMQC, which
are also indicative of the R-stereochemistry.
Synthesis of Target Glycolipids. Having the sugar moieties
of the glycolipid targets in hand, we next explored their coup-
ling with fatty acid counterparts to obtain the target glyco-
lipids. Three carboxylic acid chlorides and one carboxylic
acid were chosen to carry out the reactions: butyryl chloride,
decanoyl chloride, palmitoyl chloride, and behenic acid.
The choice of acyl chloride versus carboxylic acid was made
based on commercial availability. The difference between each
member of this homologous series of lipids is six carbon atoms.
As expected, the coupling reactions were carried out with-
out problem through the reaction of the disaccharide or
trisaccharide diol with the carboxylic acid chloride in pyridine
or with the carboxylic acid in the presence of N,N0-dicyclohexyl-
carbodiimide (DCC). The acylated compounds were next
debenzylated using palladium hydroxide on carbon under a
hydrogen atmosphere to give the target molecules in 68-93%
over the two steps, as shown in Scheme 6.
(41) Vliegenthart, J. F. G.; Dorland, L.; Vanhalbeek, H. Adv. Carbohydr.
Chem. Biochem. 1983, 41, 209–374.
(42) Reich, H. J. WinDNMR: Dynamic NMR Spectra for Windows;
Journal of Chemical Education Software, 3D2: Madison, WI, 1996.
The solvent system used in the debenzylation reactions
was a 1:1 mixture of dichloromethane and methanol. Other
solvent systems, such as methanol, a mixture of THF and
J. Org. Chem. Vol. 75, No. 15, 2010 4997

Liu et al.
JOCArticle
SCHEME 6. Synthesis of Disaccharide Glycolipids 3-6 and Trisaccharide Glycolipids 8-11
2JH,H, 3JH,H, or 4JH,H values. The coupling constants for the
disaccharides are shown in Table 3, and those for the tri-
saccharides are given in Table 4. The chemical shifts can be
found in the Supporting Information, along with representa-
tive examples of the simulated spectra. Assignment of H-5R
and H-5S was based on comparison with previous literature,43,44
and the 2JH-5R,H-5S values are assumed to be negative.45 At
the concentrations used to measure the coupling constants,
no broadening of signals was observed, suggesting that the
compounds are not aggregating.
TABLE 3. 2JH,H, 3JH,H, and 4JH,H (Hz) Values for Disaccharide 2 and
Disaccharide Glycolipids 3-6
ring
coupling
2a
3a
3b
4b
5b
6b
C
3JH-1,H-2
4JH-1,H-3
3JH-2,H-3
3JH-3,H-4
3JH-4,H-5R
3JH-4,H-5S
2.2
2.1
2.1
2.1
2.1
2.1
0.7
5.0
7.6
5.0
2.8
0.0
4.6
7.5
6.3
3.1
0.0
4.6
7.5
6.3
3.1
0.0
4.6
7.5
6.4
3.1
0.5
4.7
7.5
6.3
3.1
0.0
4.6
7.4
6.4
3.1
2JH-5R,H-5S -12.1 -12.0 -11.9 -12.0 -12.0 -11.9
E
3JH-1,H-2
4JH-1,H-3
3JH-2,H-3
3JH-3,H-4
3JH-4,H-5R
3JH-4,H-5S
4.4
0.0
8.0
6.8
6.2
3.1
4.5
0.0
7.8
7.2
7.2
3.8
4.5
0.0
7.8
7.2
6.3
4.5
4.5
0.0
7.7
7.2
6.3
4.9
4.4
0.0
7.4
7.3
7.5
3.3
4.5
0.0
7.4
7.3
6.7
3.8
The data above demonstrate that acylation has no signi-
ficant effect on ring conformation as the values for 3JH-1,H-2
,
3JH-2,H-3, 3JH-3,H-4, and 4JH-1,H-3 do not change between com-
pound 2 and 3-6 or between 7 and 8-11. Unsurprisingly,
when the coupling constants are analyzed in a standard pro-
gram for determining furanose ring conformation, PSEUROT,46
the same ring conformations and populations are predicted
for 2 as for 3-6, as well as for 7 and 8-11 (data not shown).
Additionally, changing the NMR solvent from CD3OD to
1:1 CD3OD-CDCl3 for 3 and 10 appears to have no
significant effect on ring conformation. Because the chemical
shifts for the ring protons do not change upon acylation of
O-5, we assume that rotation about the glycosidic linkages
also remains the same for all of the compounds.
2JH-5R,H-5S -12.1 -11.8 -12.0 -12.0 -11.7 -11.8
aCD3OD as solvent. bCD3OD-CDCl3 (1:1) as solvent.
C-4-C-5 bond of ring B in the trisaccharides is expected to
remain unchanged between 7 and 8-11. Using methods
described previously,43,44,47 we calculated rotamer popula-
tions about the C-4-C-5 bond for the terminal rings in
compounds 2-6 and 7-11. Equations 1 and 2, Karplus
relationships48 derived specifically for the arabinofuranose
ring,49 were used for the parent saccharides 2 and 7.
The values for 3JH-4,H-5R and 3JH-4,H-5S appear to change
more significantly upon acylation, and thus we decided
to investigate the rotamer populations about the C-4-C-5
bond in more detail. We focused on rings C, D, and E, which
have free 5-OH groups in 2 or 7; the conformation about the
3JH-4;H-5R ¼ 5:23 þ 0:02cosðφ þ 15:1°Þ
þ 4:67cosð2φ þ 30:2°Þ
ð1Þ
ð2Þ
3JH-4;H-5S ¼ 4:95 - 0:42cosðφÞ þ 4:03cosð2φÞ
(43) Serianni, A. S.; Barker, R. Can. J. Chem. 1979, 57, 3160–3167.
(44) Wu, G. D.; Serianni, A. S.; Barker, R. J. Org. Chem. 1983, 48, 1750–
1757.
€
(45) Pretsch, E.; Buhlmann, P.; Affolter, C. Structure and Determination
(47) Taha, H. A.; Castillo, N.; Roy, P.-N.; Lowary, T. L. J. Chem. Theory
Comput. 2009, 5, 430–438.
(48) Karplus, M. J. Am. Chem. Soc. 1963, 85, 2870–2871.
(49) Taha, H. A.; Castillo, N.; Sears, D. N.; Wasylishen, R. E.; Lowary,
T. L. J. Chem. Theory Comput. 2010, 6, 212–222.
of Organic Compounds, 3rd ed.; Springer-Verlag: New York, 2000; p 166.
(46) van Wijk, J.; Haasnoot, C. A. G.; de Leeuw, F. A. A. M.; Huckriede,
B. D.; Westra Hoekzema, A.; Altona, C. PSEUROT 6.3; Leiden Institute of
Chemistry, Leiden University, 1999.
4998 J. Org. Chem. Vol. 75, No. 15, 2010

Liu et al.
JOCArticle
FIGURE 2. Three staggered rotamers about the C-4-C-5 bond of arabinofuranose.
TABLE 4. 2JH,H, 3JH,H, and 4JH,H (Hz) Values for Trisaccharide 7 and
Trisaccharide Glycolipids 8-11
TABLE 5. Calculated C-4-C-5 Rotamer Distributions (%) for
Disaccharides 2-6
ring
coupling
7a
8a
9a
10a
10b
11b
ring
rotamer
2a
3a
3b
4b
5b
6b
B
3JH-1,H-2
4JH-1,H-3
3JH-2,H-3
3JH-3,H-4
3JH-4,H-5R
3JH-4,H-5S
1.4
1.5
1.5
1.5
1.2
1.2
C
gg
gt
tg
gg
gt
tg
52
47
1
35
59
6
50
46
3
21
57
21
50
46
3
27
46
27
48
48
4
20
46
33
50
46
3
24
61
15
48
48
4
31
51
18
0.7
2.8
6.0
3.2
4.9
0.6
2.9
6.1
3.0
5.1
0.5
2.9
6.0
2.9
4.9
0.6
2.9
6.2
2.8
4.9
0.6
2.4
5.5
3.0
4.4
0.6
2.4
5.5
3.0
4.5
E
2JH-5R,H-5S -11.1 -11.1 -11.2 -11.2 -11.1 -11.2
aCD3OD as solvent. bCD3OD-CDCl3 (1:1) as solvent.
C
3JH-1,H-2
4JH-1,H-3
3JH-2,H-3
3JH-3,H-4
3JH-4,H-5R
3JH-4,H-5S
1.6
0.7
3.4
6.0
5.4
3.4
1.7
0.6
3.6
6.2
6.0
3.6
1.7
0.7
3.6
6.1
6.0
3.6
1.6
0.6
3.5
6.2
6.2
3.6
1.6
0.7
3.4
5.8
6.1
3.5
1.6
0.5
3.3
5.8
6.1
3.5
TABLE 6. Calculated C-4-C-5 Rotamer Distributions (%) for
Trisaccharides 7-11
ring
rotamer
7a
8a
9a
10a
10b
11b
2JH-5R,H-5S -11.9 -11.8 -11.8 -11.7 -11.5 -11.5
C
gg
gt
tg
gg
gt
tg
43
47
10
43
50
7
48
43
10
49
44
7
48
43
10
47
45
8
44
45
11
45
46
8
48
44
9
44
45
11
48
44
9
44
45
11
D
3JH-1,H-2
4JH-1,H-3
3JH-2,H-3
3JH-3,H-4
3JH-4,H-5R
3JH-4,H-5S
1.7
0.6
3.8
6.6
5.5
3.2
1.8
0.7
4.1
7.1
6.1
3.4
1.8
0.7
4.0
7.0
6.2
3.4
1.8
0.5
4.0
6.9
6.3
3.4
1.8
0.7
4.0
6.4
6.2
3.6
1.8
0.6
3.9
6.6
6.2
3.6
D
aCD3OD as solvent. bCD3OD-CDCl3 (1:1) as solvent.
2JH-5R,H-5S -12.0 -11.9 -11.9 -11.9 -11.9 -11.9
aCD3OD as solvent. bCD3OD-CDCl3 (1:1) as solvent.
rotamers for the parent disaccharides 2 and 7 are comparable
to those for the monosaccharides methyl R-D-arabinofuranoside
and methyl β-D-arabinofuranoside. In CD3OD, we found
methyl R-D-arabinofuranoside is 45% gg: 47% gt: 8% tg and
methyl β-D-arabinofuranoside is 19% gg: 65% gt: 16% tg.
Similar populations have been reported for both mono-
saccharides in D2O, as well.47,51
The angle φ is the dihedral angle between the coupled pro-
tons. These equations were solved to give the maximal
coupling constants for the three staggered conformations
about the C-4-C-5 bond, where φ = 60, 180, and -60°
(Figure 2).40,44,47 The coupling constants measured in solu-
tion represent a weighted average of these staggered confor-
mations; the population of each conformation was deter-
mined for each ring using eqs 3-5 below:
For the acylated saccharides 3-6 and 8-11, we developed
new Karplus-type relationships for 3JH-4,H-5R and 3JH-4,H-5S
in arabinofuranose rings using DFT calculations; the meth-
ods are detailed in the Supporting Information. The newly
3JH-4;H-5R ¼ 1:18Xgg þ 9:25Xgt þ 5:26Xtg
3JH-4;H-5S ¼ 2:73Xgg þ 2:73Xgt þ 9:40Xtg
1 ¼ Xgg þ Xgt þ Xtg
ð3Þ
ð4Þ
ð5Þ
3
3
derived eqs 6 and 7 describe the JH-4,H-5R and JH-4,H-5S
relationships for both anomers of methyl 5-O-acetyl-R-D-
arabinofuranoside.
3JH-4;H-5R ¼ 5:27 - 0:51cosðφÞ þ 4:83cosð2φÞ
Equations 3-5 were solved for compounds 2 and 7, and
the gg and gt rotamers were found to be favored over the tg
rotamer, as expected due to the gauche effect.50 The results
for 2 are in Table 5, and the results for 7 are in Table 6. For
the R-linked rings (C of 2, C and D of 7), the gg and gt
rotamers are about equally populated, giving average values
of 46 ( 5% gg:48 ( 2% gt:6 ( 5% tg. For the β-linked ring E
in 2, however, the population of the gt rotamer was signifi-
cantly higher than the gg rotamer; the tg conformation re-
mained relatively minor: 35% gg:59% gt:6% tg. The C-4-C-5
þ 0:02sinðφÞ - 0:04sinð2φÞ
ð6Þ
3JH-4;H-5S ¼ 5:34 - 0:62cosðφÞ þ 4:50cosð2φÞ
þ 0:07sinðφÞ þ 2:06sinð2φÞ
ð7Þ
Again, the angle φ is the dihedral angle between the coupled
protons. These equations were solved to give the coupl-
ing constants for the staggered conformations about the
(51) Seo, M.; Castillo, N.; Ganzynkowicz, R.; Daniels, C. R.; Woods,
R. J.; Lowary, T. L.; Roy, P.-N. J. Chem. Theory Comput. 2008, 4, 184–191.
(50) Wolfe, S. Acc. Chem. Res. 1972, 5, 102–111.
J. Org. Chem. Vol. 75, No. 15, 2010 4999

Liu et al.
JOCArticle
reducing end of the mAG complex present in the mycobac-
terial cell wall. A key step in the synthesis of the disaccharides
was the use of an allyl-protected thioglycoside donor with a
p-methoxybenzyl-protected acceptor to afford the desired
β-(1f2) linkage with good selectivity and high yield. Both
the R-(1f3) and R-(1f5) linkages of the trisaccharides were
formed in excellent yield using a one-pot protocol.
We analyzed the conformation of the final compounds
using solution-state NMR spectroscopy to determine all
proton-proton coupling constants, and we determined that
there was little effect on the ring conformation upon acyla-
tion at O-5. In order to see a change in ring conformation,
it may be necessary to used branched acyl chains or explore larger
compounds, for example, the hexasaccharide shown in Figure 1,
which more closely mimic the natural system. We did, however,
see a significant increase in the tg rotamer about the C-4-C-5
bond in the β-arabinofuranoside rings present in disaccharides
3-6 upon acylation, suggesting that the lipid chain has some
effect on the conformation of the hydroxymethyl group.
FIGURE 3. Methyl 5-O-acetyl-β-D-arabinofuranoside showing the
hydrogen bond (green dashed line) from the 3-OH to the carbonyl
oxygen of the acetate. This conformation is 2.6 kcal/mol lower in
energy than the corresponding conformation without a hydrogen
bond, and the distance between the hydrogen and carbonyl oxygen
˚
is 2.02 A. The single point energy was calculated using B3LYP/
6-31G(d)52,53 in Gaussian03.54 The image was created in PyMol.55
Experimental Section
C-4-C-5 bond, as described above, to give eqs 8-10 below:
General Procedure for Hydrogenolysis Leading to 2-6 and
8-11. To a solution of starting material (0.02 mmol) in CH2Cl2
(1 mL) and CH3OH (1 mL) was added 20% Pd(OH)2-C
(0.15-0.20 fold by weight) at room temperature. The reaction
was stirred under a positive pressure of hydrogen for 12 h. The
resulting mixture was filtered through Celite and concentrated.
The crude residue was purified on Iatrobeads with CH2Cl2-
CH3OH as the eluent.
3JH-4;H-5R ¼ 2:58Xgg þ 10:62Xgt þ 2:63Xtg
3JH-4;H-5S ¼ 4:50Xgg þ 1:05Xgt þ 10:46Xtg
1 ¼ Xgg þ Xgt þ Xtg
ð8Þ
ð9Þ
ð10Þ
General Procedures for Glycosylations Leading to 23-28. The
acceptor (0.30 mmol) and donor (0.45 mmol) were dried under
vacuum in the presence of P2O5 for 2 h. To this mixture were
Equations 8-10 were solved for compounds 3-6 and
8-11, and the rotamer populations for the disaccharides
3-6 can be found in Table 5 and those for the trisaccharides
8-11 can be found in Table 6. No significant differences in
the rotamer populations were seen for the R-linked ring C of
3-6 or rings C and D of 8-11 when compared to the same
rings in 2 and 7. In the acylated species, the gg and gt con-
formations were still favored and were present in about equal in
population, with an overall average population of 47 ( 2% gg:45
( 2% gt:8 ( 3% tg for these rings. However, unlike the R-linked
rings, there was a significant change in the β-linked ring E in
compounds 3-6. The tg population increased from 6% in the
unacylated disaccharide 2 to an average 23% in compounds 3-6,
with concomitant decreases in both the gg and gt conformations,
to give an average rotamer distribution of 25 ( 4% gg:52 ( 7%
gt:23 ( 7% tg for the β-linked rings. One possible explanation for
the increase of the tg rotamer is that in this conformation the
carbonyl oxygen of the acyl group is in the proper orientation to
form a weak hydrogen bond to the 3-hydroxyl group, as illu-
strated in Figure 3. Such interactions would also be anticipated to
be important in the relatively hydrophobic outer leaflet of the
mycobacterial cell wall, where it is anticipated only limited
amounts of water would be present.
˚
added CH2Cl2 (30 mL) and 4 A molecular sieves (0.10 g). The
reaction was allowed to stir at room temperature for 30 min and
cooled to -60 °C, followed by the addition of N-iodosuccin-
imide (0.36 mmol) and silver triflate (0.03 mmol). After the
temperature rose to -40 °C, the reaction mixture turned dark
red/brown. Triethylamine was added to quench the reaction
after TLC indicated the completion of reactions. The solution
was then diluted with CH2Cl2 and filtered through Celite. The
filtrate was concentrated to give a crude residue that was puri-
fied by chromatography to obtain the product.
General Procedure for Acylation Using Carboxylic Acid Chlo-
rides Leading to 35-37 and 39-41. To a solution of the alcohol
(0.06 mmol) in CH2Cl2 (2 mL) and pyridine (0.05 mL) was
added the carboxylic acid chloride (0.15 mmol) at 0 °C. The
reaction was kept stirring for 2 h and quenched by the addition
of CH3OH. The resulting solution was concentrated, and the
residue was purified by chromatography (4:1 hexane-EtOAc)
to obtain the acylated compound.
General Procedure for Acylation Using Behenic Acid Leading
to 38 and 42. To a solution of alcohol (0.10 mmol) in CH2Cl2
(3 mL) were added behenic acid (131 mg, 0.38 mmol), DCC (79 mg,
0.38 mol), and DMAP (5 mg) at 0 °C. The reaction was kept
stirring for 4 h and quenched by the addition of CH3OH. The
resulting solution was concentrated, and the residue was puri-
fied by chromatography (10:1 hexane-EtOAc) to obtain the
acylated product as a white solid.
Methyl β-D-arabinofuranosyl-(1f2)-r-D-arabinofuranoside (2):
Isolated as a colorless oil, 85%; Rf 0.37 (7:1 CH2Cl2-CH3OH);
[R]D -23.2 (c 1.0, CH3OH); 1H NMR (600 MHz, CD3OD, δH)
4.95 (d, 1 H, J1E,2E = 4.2 Hz, H-1E), 4.87 (d, 1 H, J1C,2C = 2.1
Hz, H-1C), 4.06-3.95 (m, 4 H, H-2C, H-3C, H-3E, H-2E), 3.88
(ddd, 1 H, J3C,4C =2.6 Hz, J4C,5Ca =4.9 Hz, J4C,5Cb =7.4 Hz,
Conclusions
In conclusion, we describe here the synthesis of a series of
glycolipids (3-6 and 8-11) as simple mimics of the non-
(52) Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.
(53) Rassolov, V. A.; Ratner, M. A.; Pople, J. A.; Redfern, P. C.; Curtiss,
L. A. J. Comput. Chem. 2001, 22, 976–984.
(54) Frisch, M. J.; et al. Gaussian 03, revision C.02; Gaussian, Inc.:
Wallingford, CT, 2004.
H-4C), 3.81-3.75 (m, 2 H, H-5Ca, H-4E), 3.72 (dd, 1 H, J4E,5Ea
=
(55) DeLano, W. L. The PyMol Molecular Graphics System; DeLano
Scientific: Palo Alto, CA, 2002.
3.2 Hz, J5Ea,5Eb =11.8 Hz, H-5Ea), 3.67-3.60 (m, 2 H, H-5Eb,
5000 J. Org. Chem. Vol. 75, No. 15, 2010

Liu et al.
JOCArticle
H-5Cb), 3.37 (s, 1 H, OCH3); 13C NMR (125 MHz, CDCl3, δC)
108.4 (C-1C), 102.5 (C-1E), 89.5 (C-2E), 84.3 (C-4E), 83.8 (C-4C),
78.8 (C-3C), 76.4 (C-2C), 75.8 (C-3E), 64.4 (C-5E), 62.4 (C-5C),
55.4 (OCH3); ESIMS m/z calcd for [C11H20O9Na]þ 319.1000,
found 319.0994.
1H NMR (600 MHz, 1:1 CDCl3-CD3OD, δH) 4.98 (d, 1 H,
J
1E,2E = 4.4 Hz, H-1E), 4.87 (d, 1 H, J1C,2C=2.1 Hz, H-1C),
4.31 (dd, 1 H, J4C,5Ca = 3.1 Hz, J5Ca,5Cb = 11.9 Hz, H-5Ca),
4.24-4.20 (m, 2 H, H-5Ea, H-5Eb), 4.14 (dd, 1 H, J4C,5Cb =6.3
Hz, J5Ca,5Cb=11.9 Hz, H-5Cb), 4.06 (ddd, 1 H, J3C,4C=7.5 Hz,
Methyl 5-O-butyryl-β-D-arabinofuranosyl-(1f2)-5-O-butyryl-
r-D-arabinofuranoside (3): Isolated as a colorless oil, 97%; Rf
J4C,5Ca=3.1 Hz, J4C,5Cb=6.3 Hz, H-4C), 4.00 (dd, 1 H, J1C,2C=
2.1 Hz, J2C,3C=4.7 Hz, H-2C), 3.99-3.91 (m, 4 H, H-2E, H-3C,
H-3E, H-4E), 3.36 (s, 3 H, OCH3), 2.36-2.30 (m, 4 H, CH2ꢀ2),
1.64-1.56 (m, 4 H, CH2 ꢀ 2), 1.40-1.06 (m, 72 H, CH2 ꢀ 36),
0.90-0.78 (m, 6 H, CH3 ꢀ 2); 13C NMR (125 MHz, 1:1
CDCl3-CD3OD, δC) 175.7 (CdO), 175.6 (CdO), 108.4 (C-
1C), 103.1 (C-1E), 90.0 (C-2C), 81.5 (C-4E), 81.2 (C-4C), 78.5
(C-2E), 77.3 (C-3C), 76.7 (C-3E), 67.0 (C-5E), 65.0 (C-5C), 56.2
(OCH3), 35.3 (acyl CH2), 33.2 (acyl CH2), 30.9(4) (acyl CH2),
30.9(4) (acyl CH2), 30.9(1) (acyl CH2), 30.8 (acyl CH2), 30.6(1)
(acyl CH2), 30.5(7) (acyl CH2), 30.4(1) (acyl CH2), 30.3(9) (acyl
CH2), 26.1(7) (acyl CH2), 26.1(4) (acyl CH2), 23.9 (acyl CH2),
15.0 (acyl CH3 ꢀ 2); ESIMS m/z calcd for [C55H104O11Na]þ
963.7471, found 963.7472.
1
0.29 (20:1 CH2Cl2-CH3OH); [R]D þ1.7 (c 1.3, CH3OH); H
NMR (500 MHz, 1:1 CDCl3/CD3OD, δH) 4.98 (d, 1 H, J1E,2E=
4.4 Hz, H-1E), 4.87 (d, 1 H, J1C,2C = 2.1 Hz, H-1C), 4.31 (dd,
1 H, J4E,5Ea=3.1 Hz, J5Ea,5Eb=11.9 Hz, H-5Ea), 4.25-4.19 (m,
2 H, H-5Ca, H-5Cb), 4.14 (dd, 1 H, J4E,5Eb =6.3 Hz, J5Ea,5Eb=
11.9 Hz, H-5Eb), 4.07-3.92 (m, 6 H, H-4C, H-2C, H-2E, H-3C,
H-3E, H-4E), 3.38 (s, 3 H, OCH3), 2.34-2.30 (m, 4 H, CH2ꢀ2),
1.68-1.58 (m, 4 H, CH2 ꢀ2), 0.96-0.90 (m, 6 H, CH3 ꢀ2); 13
C
NMR (125 MHz, 1:1 CDCl3/CD3OD, δC) 175.5 (CdO), 175.4
(CdO), 108.4 (C-1C), 103.0 (C-1E), 89.8 (C-2C), 81.5 (C-4E),
81.3 (C-4C), 78.5 (C-2E), 77.2 (C-3C), 76.7 (C-3E), 67.1 (C-5E),
64.9 (C-5C), 56.1 (OCH3), 37.2 (acyl CH2 ꢀ 2), 19.5(8) (acyl
CH2), 19.5(5) (acyl CH2), 14.4(8) (acyl CH3), 14.4(6) (acyl CH3);
ESIMS m/z calcd for [C19H32O11Na]þ 459.1837, found 459.1834.
Methyl 5-O-decanoyl-β-D-arabinofuranosyl-(1f2)-5-O-decanoyl-
r-D-arabinofuranoside (4): Isolated as a colorless oil, 92%; Rf
Methyl 5-O-butyryl-r-D-arabinofuranosyl-(1f3)-[5-O-butyryl-
r-D-arabinofuranosyl-(1f5)]-r-D-arabinofuranoside (8): Isolated
as a colorless oil, 79%; Rf 0.29 (10:1 CH2Cl2-CH3OH); [R]D
þ
140.7 (c 0.4, CH3OH); 1H NMR (600 MHz, 1:1 CDCl3/CD3OD,
δH) 5.00(d, 1 H, J1D,2D=1.8 Hz, H-1D), 4.97 (d, 1 H, J1C,2C=1.4
Hz, H-1C), 4.77 (s, 1 H, H-1B), 4.30-4.25 (m, 2 H, H-5Ca, H-5
Da), 4.19-4.10 (m, 4 H, H-5Cb, H-5Db, H-4C, H-4B), 4.06 (dd,
1 H, J1B,2B=1.2 Hz, J2B,3B=2.4 Hz, H-2B), 4.05-4.00 (m, 3 H,
H-2C, H-2D, H-4D), 3.97 (dd, 1 H, J2B,3B =2.4 Hz, J3B,4B=5.5
Hz, H-3B), 3.93 (dd, 1 H, J4B,5Ba = 4.6 Hz, J5Ba,5Bb = 11.2 Hz,
1
0.41 (10:1 CH2Cl2-CH3OH); [R]D þ0.6 (c 1.3, CH3OH); H
NMR (600 MHz, 1:1 CDCl3/CD3OD, δH) 4.98 (d, 1 H, J1E,2E
=
4.5 Hz, H-1E), 4.87 (d, 1 H, J1C,2C = 2.1 Hz, H-1C), 4.32 (dd,
1 H, J4C,5Ca=3.1 Hz, J5Ca,5Cb=12.0 Hz, H-5Ca), 4.24-4.20 (m,
2 H, H-5Ea, H-5Eb), 4.14 (dd, 1 H, J4C,5Cb=6.3 Hz, J5Ca,5Cb=
12.0 Hz, H-5Cb), 4.06 (ddd, 1 H, J3C,4C =7.5 Hz, J4C,5Ca =3.1
Hz, J4C,5Cb = 6.3 Hz, H-4C), 4.01 (dd, 1 H, J1C,2C = 2.1 Hz,
J2C,3C=4.5 Hz, H-2C), 4.00-3.91 (m, 4 H, H-2E, H-3C, H-3E,
H-4E), 3.36 (s, 3 H, OCH3), 2.36-2.30 (m, 4 H, CH2 ꢀ 2),
1.64-1.54 (m, 4 H, CH2 ꢀ 2), 1.34-1.08 (m, 24 H, CH2 ꢀ 12),
0.88-0.82 (m, 6 H, CH3 ꢀ2); 13C NMR (125 MHz, 1:1 CDCl3/
CD3OD, δC) 175.7 (CdO), 175.6 (CdO), 108.4 (C-1C), 103.0
(C-1E), 89.8 (C-2C), 81.5 (C-4E), 81.3 (C-4C), 78.5 (C-2E), 77.2
(C-3C), 76.7 (C-3E), 67.1 (C-5E), 65.0 (C-5C), 56.2 (OCH3), 35.4
(acyl CH2), 35.3(2) (acyl CH2), 35.3(1) (acyl CH2), 33.1 (acyl
CH2), 30.7 (acyl CH2), 30.5(4) (acyl CH2), 30.5(2) (acyl CH2),
30.4(0) (acyl CH2), 30.3(8) (acyl CH2), 30.3(6) (acyl CH2),
26.2(3) (acyl CH2), 26.1(5) (acyl CH2), 26.1(2) (acyl CH2), 23.9
(acyl CH2), 15.0 (acyl CH3 ꢀ 2); ESIMS m/z calcd for [C31H56-
O11Na]þ: 627.3715, found 627.3717.
H-5Ba), 3.81-3.78 (m, 2 H, H-3C, H-3D), 3.68 (dd, 1 H, J4B,5Bb
=
3.0 Hz, J5Ba,5Bb = 11.2 Hz, H-5Bb), 3.38 (s, 3 H, OCH3),
2.34-2.30 (m, 4 H, acyl CH2 ꢀ 2), 1.66-1.60 (m, 4 H, acyl CH2 ꢀ
2), 0.95-0.90 (m, 6 H, acyl CH3 ꢀ 2); 13C NMR (125 MHz, 1:1
CDCl3/CD3OD, δC) 175.4(6) (CdO), 175.4(5) (CdO), 110.6
(C-1B), 109.6 (C-1C), 109.3 (C-1D), 84.9 (C-3B), 83.4 (C-4D),
83.2(2) (C-4C), 83.1(9) (C-4B), 82.7 (C-2D), 82.5 (C-2C), 81.7
(C-2B), 79.1(0) (C-3D), 79.0(6) (C-3C), 67.9 (C-5B), 65.4 (C-5C),
65.1 (C-5D), 55.9 (OCH3), 37.1(8) (acyl CH2), 37.1(8) (acyl CH2),
19.6 (acyl CH2 ꢀ 2), 14.5(4) (acyl CH3), 14.5(2) (acyl CH3);
ESIMS m/z calcd for [C24H40O15Na]þ 591.2259, found 591.2257.
Methyl 5-O-decanoyl-r-D-arabinofuranosyl-(1f3)-[5-O-decanoyl-
r-D-arabinofuranosyl-(1f5)]-r-D-arabinofuranoside (9): Isolated
as a colorless oil, 86%; Rf 0.38 (10:1 CH2Cl2-CH3OH); [R]D
115.0 (c 1.1, CH3OH); 1H NMR (600 MHz, 1:1 CDCl3-CD3OD,
δH) 5.00 (d, 1 H, J1D,2D =1.8 Hz, H-1D), 4.97 (d, 1 H, J1C,2C
þ
Methyl 5-O-palmitoyl-β-D-arabinofuranosyl-(1f2)-5-O-palmitoyl-
r-D-arabinofuranoside (5). Isolated as a colorless oil, 95%; Rf
0.53 (10:1 CH2Cl2-CH3OH); [R]D þ2.7 (c 2.6, CHCl3); 1H
=
1.3 Hz, H-1C), 4.77 (s, 1 H, H-1B), 4.30-4.24 (m, 2 H, H-5Ca,
H-5 Da), 4.18-4.10 (m, 4 H, H-5Cb, H-5Db, H-4C, H-4B), 4.06
(dd, 1 H, J1B,2B=1.2 Hz, J2B,3B=2.4 Hz, H-2B), 4.05-4.00 (m, 3
NMR (600 MHz, 1:1 CDCl3/CD3OD, δH) 4.98 (d, 1 H, J1E,2E
=
4.5 Hz, H-1E), 4.87 (d, 1 H, J1C,2C = 2.1 Hz, H-1C), 4.31 (dd,
1 H, J4C,5Ca=3.1 Hz, J5Ca,5Cb=11.9 Hz, H-5Ca), 4.23-4.21 (m,
2 H, H-5Ea, H-5Eb), 4.14 (dd, 1 H, J4C,5Cb=6.3 Hz, J5Ca,5Cb=
11.9 Hz, H-5Cb), 4.06 (ddd, 1 H, J3C,4C =7.5 Hz, J4C,5Ca =3.1
Hz, J4C,5Ca = 6.3 Hz, H-4C), 4.01 (dd, 1 H, J1C,2C = 2.1 Hz,
H, H-2C, H-2D, H-4D), 3.99 (dd, 1 H, J2B,3B =2.4 Hz, J3B,4B
5.5 Hz, H-3B), 3.94 (dd, 1 H, J4B,5Ba=4.6 Hz, J5Ba,5Bb=11.2 Hz,
H-5Ba), 3.82-3.78 (m, 2 H, H-3C, H-3D), 3.68 (dd, 1 H, J4B,5Bb
=
=
3.0 Hz, J5Ba,5Bb=11.2 Hz, H-5Bb), 3.34 (s, 3 H, OCH3), 2.36-2.31
(m, 4 H, acyl CH2ꢀ2), 1.62-1.56 (m, 4 H, acyl CH2ꢀ2), 1.34-1.20
J2C,3C=4.7 Hz, H-2C), 4.00-3.91 (m, 4 H, H-2E, H-3C, H-3E,
H-4E), 3.36 (s, 3 H, OCH3), 2.36-2.30 (m, 4 H, CH2 ꢀ 2),
1.64-1.56 (m, 4 H, CH2 ꢀ 2), 1.34-1.18 (m, 48 H, CH2 ꢀ 24),
0.88-0.82 (m, 6 H, CH3 ꢀ2); 13C NMR (125 MHz, 1:1 CDCl3/
CD3OD, δC) 175.7 (CdO), 175.6 (CdO), 108.4 (C-1C), 103.0
(C-1E), 89.8 (C-2C), 81.5 (C-4E), 81.2 (C-4C), 78.5 (C-2E), 77.2
(C-3C), 76.7 (C-3E), 67.0 (C-5E), 65.0 (C-5C), 56.2 (OCH3),
35.3(2) (acyl CH2), 35.3(1) (acyl CH2), 33.2 (acyl CH2), 30.9(4)
(acyl CH2), 30.9(1) (acyl CH2), 30.8(8) (acyl CH2), 30.7(5) (acyl
CH2), 30.6(1) (acyl CH2), 30.5(6) (acyl CH2), 30.4(0) (acyl CH2),
30.3(8) (acyl CH2), 26.1(7) (acyl CH2), 26.1(3) (acyl CH2), 23.9
(acyl CH2), 15.0 (acyl CH3 ꢀ 2); ESIMS m/z calcd for [C43H80-
O11Na]þ: 795.5593, found 795.5589.
(m, 24 H, acyl CH2 ꢀ 12), 0.87-0.82 (m, 6 H, acyl CH3 ꢀ 2); 13
C
NMR (125 MHz, 1:1 CDCl3/CD3OD, δC) 175.6(4) (CdO),
175.6(3) (CdO), 110.6 (C-1B), 109.6 (C-1C), 109.3 (C-1D), 84.8
(C-3B), 83.4 (C-4D), 83.3 (C-4C), 83.2 (C-4B), 82.7 (C-2D), 82.6
(C-2C), 81.7 (C-2B), 79.1(4) (C-3D), 79.0(8) (C-3C), 67.8 (C-5B),
65.4 (C-5C), 65.2 (C-5D), 55.9 (OCH3), 35.3(1) (acyl CH2), 35.2(9)
(acyl CH2), 33.1 (acyl CH2), 30.7 (acyl CH2), 30.6 (acyl CH2),
30.5(4) (acyl CH2), 30.5(3) (acyl CH2), 30.4(1) (acyl CH2), 30.3(9)
(acyl CH2), 26.1 (acyl CH2), 23.9 (acyl CH2), 15.0 (acyl CH3);
ESIMS m/z calcd for [C36H64O15Na]þ 759.4137, found 759.4137.
Methyl 5-O-palmitoyl-r-D-arabinofuranosyl-(1f3)-[5-O-palmi-
toyl-r-D-arabinofuranosyl-(1f5)]-r-D-arabinofuranoside (10):
Methyl 5-O-behenoyl-β-D-arabinofuranosyl-(1f2)-5-O-behenoyl-
r-D-arabinofuranoside (6): Isolated as a colorless oil, 92%;
Rf 0.61 (10:1 CH2Cl2-CH3OH); [R]D þ4.2 (c 1.7, CHCl3);
Isolated as a colorless oil, 89%; Rf 0.47 (10:1 CH2Cl2-CH3OH);
1
[R]D þ64.4 (c 0.4, CHCl ); H NMR (600 MHz, 1:1 CDCl3-
3
CD3OD, δH) 5.00 (d, 1 H, J1D,2D=1.7 Hz, H-1D), 4.97 (d, 1 H,
J. Org. Chem. Vol. 75, No. 15, 2010 5001

Liu et al.
JOCArticle
J1C,2C =1.3 Hz, H-1C), 4.77 (s, 1 H, H-1B), 4.30-4.24 (m, 2 H,
H-5Ca, H-5 Da), 4.18-4.09 (m, 4 H, H-5Cb, H-5Db, H-4C,
H-4B), 4.05 (dd, 1 H, J1B,2B = 1.2 Hz, J2B,3B = 2.3 Hz, H-2B),
CH2O), 69.2 (C-5), 21.1 (tolyl CH3); ESIMS m/z calcd for
[C29H32O4SNa]þ 499.1914, found 499.1911.
p-Tolyl 2,3-di-O-benzyl-5-O-tert-butyldimethylsilyl-1-thio-r-
D-arabinofuranoside (15). To a solution of compound 18 (57 mg,
0.13 mmol) in CH2Cl2 (1.3 mL) tert-butyldimethylsilyl chloride
(50 mg, 0.33 mmol) were added imidazole (45 mg, 0.60 mmol) and
DMAP (10 mg). The solution was stirred for 2 h, and then the
reaction was quenched by the addition of CH3OH. The solution
was concentrated, and the residue was purified by chromatography
(4:1 hexane-EtOAc) to obtain 15 (54 mg, 75%) as a colorless
syrup: Rf 0.32 (4:1 hexane-EtOAc); [R]D þ76.6 (c 0.5, CHCl3); 1H
NMR (500 MHz, CDCl3, δH) 7.47-7.41 (m, 2 H, Ar), 7.40-7.29
(m, 10 H, Ar), 7.15-7.11 (m, 2 H, Ar), 5.52 (d, 1 H, J1,2=3.0 Hz,
H-1), 4.67 (d, 1 H, J=11.9 Hz, PhCH2O), 4.60 (s, 2 H, PhCH2O),
4.54 (d, 1 H, J=11.8 Hz, PhCH2O), 4.28 (ddd, 1 H, J3,4=6.3 Hz,
J4,5a=4.4 Hz, J4,5b=4.6 Hz, H-4), 4.15 (dd, 1 H, J1,2=J2,3=3.0
Hz, H-2), 4.06 (dd, 1 H, J2,3=3.0 Hz, J3,4=6.3 Hz, H-3), 3.82 (dd,
4.04-4.00 (m, 3 H, H-2C, H-2D, H-4D), 3.99 (dd, 1 H, J2B,3B
2.3 Hz, J3B,4B =5.5 Hz, H-3B), 3.94 (dd, 1 H, J4B,5Ba =4.5 Hz,
5Ba,5Bb = 11.1 Hz, H-5Ba), 3.82-3.78 (m, 2 H, H-3C, H-3D),
=
J
3.68 (dd, 1 H, J4B,5Bb=3.0 Hz, J5Ba,5Bb=11.1 Hz, H-5Bb), 3.34
(s, 3 H, OCH3), 2.36-2.30 (m, 4 H, acyl CH2ꢀ2), 1.64-1.54 (m,
4 H, acyl CH2 ꢀ 2), 1.34-1.16 (m, 48 H, acyl CH2 ꢀ 24),
0.88-0.80 (m, 6 H, acyl CH3 ꢀ 2); 13C NMR (125 MHz, 1:1
CDCl3/CD3OD, δC) 175.6 (CdO ꢀ 2), 110.6 (C-1B), 109.6
(C-1C), 109.4 (C-1D), 84.8 (C-3B), 83.4 (C-4D), 83.3 (C-4C),
83.2 (C-4B), 82.7 (C-2D), 82.6 (C-2C), 81.7 (C-2B), 79.1 (C-3D,
C-3C), 67.8 (C-5B), 65.4 (C-5C), 65.2 (C-5D), 55.9 (OCH3),
35.3(2) (acyl CH2), 35.3(0) (acyl CH2), 33.2 (acyl CH2), 30.9(4)
(acyl CH2), 30.9(1) (acyl CH2), 30.8(8) (acyl CH2), 30.7(7) (acyl
CH2), 30.7(6) (acyl CH2), 30.6(1) (acyl CH2), 30.6(0) (acyl CH2),
30.5(7) (acyl CH2), 30.4(3) (acyl CH2), 30.4(2) (acyl CH2), 26.1
(acyl CH2), 23.9 (acyl CH2), 15.0 (acyl CH3 ꢀ 2); ESIMS m/z
calcd for [C48H88O15Na]þ 927.6015, found 927.6014.
Methyl 5-O-behenoyl-r-D-arabinofuranosyl-(1f3)-[5-O-behenoyl-
r-D-arabinofuranosyl-(1f5)]-r-D-arabinofuranoside (11): Isolated
as a colorless oil, 84%; Rf 0.60 (10:1 CH2Cl2-CH3OH); [R]D -3.2
(c 1.3, CH3OH); 1H NMR (600 MHz, 1:1 CDCl3-CD3OD, δH)
5.00 (d, 1 H, J1D,2D=1.7 Hz, H-1D), 4.97 (d, 1 H, J1C,2C=1.2 Hz,
H-1C), 4.77 (s, 1 H, H-1B), 4.30-4.24 (m, 2 H, H-5Ca, H-5 Da),
4.19-4.10 (m, 4 H, H-5Cb, H-5Db, H-4C, H-4B), 4.05 (dd, 1 H,
1 H, J4,5a =4.4 Hz, J5a,5b =11.0 Hz, H-5a), 3.79 (dd, 1 H, J4,5b
=
4.6 Hz, J5a,5b=11.0 Hz, H-5b), 2.35 (s, 3 H, tolyl CH3), 0.92 (s, 9 H,
t-butyl CH3 ꢀ3), 0.08 (s, 6 H, TBDMS CH3 ꢀ2); 13C NMR (125
MHz, CDCl3, δC) 137.9 (Ar), 137.5 (Ar), 137.2 (Ar), 131.9 (Ar ꢀ
2), 131.1 (Ar), 129.6 (Arꢀ2), 128.4(2) (Arꢀ2), 128.3(8) (Arꢀ2),
127.9(1) (Ar ꢀ 2), 127.8(5) (Ar), 127.7(3) (Ar ꢀ 2), 127.7(1) (Ar),
90.5 (C-1), 88.4 (C-2), 83.4 (C-3), 82.2 (C-4), 72.2 (PhCH2O), 72.1
(PhCH2O), 62.7 (C-5), 25.9 (t-butyl CH3 ꢀ 3), 21.1 (tolyl CH3),
18.3 (t-butyl C), -5.2(7) (Si CH3), -5.3(4) (Si CH3); ESIMS m/z
calcd for [C32H42O4SiSNa]þ 573.2465, found 573.2463.
Methyl 5-O-benzoyl-3-O-benzyl-r-D-arabinofuranoside (16).
Compound 21 (246 mg, 0.97 mmol) was dissolved in CH2Cl2
(19 mL) and pyridine (0.47 mL), and the solution was cooled to
-10 °C. Benzoyl chloride (0.16 mL, 1.28 mmol) was added
dropwise to the mixture over a period of 30 min with stirring.
The reaction was subsequently quenched by the addition of CH3OH,
concentrated and the residue purified by chromatography (2:1
hexane-EtOAc) to obtain 16 (301 mg, 87%) as a colorless
syrup: Rf 0.32 (2:1 hexane-EtOAc); [R]D þ90.6 (c 0.4, CHCl3);
1H NMR (500 MHz, CDCl3, δH) 8.04-8.01 (m, 2 H, Ar),
7.58-7.54 (m, 1 H, Ar), 7.46-7.41 (m, 2 H, Ar), 7.34-7.24
(m, 5 H, Ar), 4.88 (s, 1 H, H-1), 4.71 (d, 1 H, J = 12.1 Hz,
PhCH2O), 4.62 (d, 1 H, J = 12.1 Hz, PhCH2O), 4.55 (dd, 1 H,
J
1B,2B=1.2 Hz, J2B,3B=2.4 Hz, H-2B), 4.04-4.01 (m, 3 H, H-2C,
H-2D, H-4D), 3.99 (ddd, 1 H, J1B,3B = 0.5 Hz, J2B,3B = 2.4 Hz,
J3B,4B =5.5 Hz, H-3B), 3.94 (dd, 1 H, J4B,5Ba =4.5 Hz, J5Ba,5Bb
=
11.2 Hz, H-5Ba), 3.82-3.77 (m, 2 H, H-3C, H-3D), 3.68 (dd, 1 H,
J4B,5Bb=2.9 Hz, J5Ba,5Bb=11.2 Hz, H-5Bb), 3.35 (s, 3 H, OCH3),
2.36-2.30 (m, 4 H, CH2 ꢀ 2), 1.64-1.54 (m, 4 H, CH2 ꢀ 2),
1.40-1.16 (m, 72 H, CH2ꢀ36), 0.88-0.80 (m, 6 H, CH3ꢀ2); 13
C
NMR (125 MHz, 1:1 CDCl3-CD3OD, δC) 175.6 (CdO ꢀ 2),
110.6 (C-1B), 109.6 (C-1C), 109.4 (C-1D), 84.8 (C-3B), 83.4
(C-4D), 83.3 (C-4C), 83.2 (C-4B), 82.7 (C-2D), 82.6 (C-2C), 81.7
(C-2B), 79.1 (C-3D, C-3C), 67.8 (C-5B), 65.4 (C-5C), 65.2 (C-5D),
55.9 (OCH3), 35.3(2) (acyl CH2), 35.3(0) (acyl CH2), 33.2 (acyl
CH2), 30.9(4) (acyl CH2), 30.9(0) (acyl CH2), 30.7(8) (acyl
CH2), 30.7(7) (acyl CH2), 30.6(1) (acyl CH2), 30.4(3) (acyl CH2),
30.4(2) (acyl CH2), 26.2 (acyl CH2), 23.9 (acyl CH2), 15.0 (acyl
CH3ꢀ2); ESIMS m/z calcd for [C60H112O15Na]þ 1095.7893, found
1095.7892.
J
4,5a=3.1 Hz, J5a,5b=11.5 Hz, H-5a), 4.43-4.35 (m, 2 H, H-5b,
H-4), 4.26 (dd, 1 H, J1,2 =1.2 Hz, J2,3 =2.5 Hz, H-2), 3.88 (dd,
1 H, J2,3= 2.5 Hz, J3,4 =5.8 Hz, H-3), 3.42 (s, 3 H, OCH3); 13
C
NMR (125 MHz, CDCl3, δC) 166.4 (CdO), 137.5 (Ar), 133.1
(Ar), 129.8 (Ar), 129.7 (Ar ꢀ 2), 128.5 (Ar ꢀ 2), 128.4 (Ar ꢀ 2),
128.0 (Ar), 127.9 (Ar ꢀ 2), 109.5 (C-1), 85.4 (C-3), 80.6 (C-2),
80.1 (C-4), 72.5 (PhCH2O), 64.3 (C-5), 55.1 (OCH3); ESIMS m/z
calcd for [C20H22O6Na]þ 381.1309, found 381.1313.
p-Tolyl 5-O-allyl-2,3-di-O-benzyl-1-thio-r-D-arabinofuranoside
(14). To a solution of compound 18 (2.34 g, 5.36 mmol) in DMF
(25 mL) were added NaH (343 mg, 8.58 mmol, 60% dispersion
in oil) and AllBr (0.70 mL, 8.04 mmol) at 0 °C. The mixture was
stirred at this temperature for 2 h, and the reaction was quen-
ched by the addition of CH3OH. The solution was diluted with
EtOAc and washed with water. The organic layer was dried
(MgSO4), concentrated, and purified by chromatography (8:1
hexane-EtOAc) to afford 14 (2.33 g, 91%) as a colorless syrup:
Methyl 3-O-benzyl-5-O-p-methoxybenzyl-r-D-arabinofurano-
side (17). To a solution of compound 22 (1.88 g, 7.06 mmol)
dissolved in benzyl alcohol (8 mL) was added 1 M BnONa in
benzyl alcohol (8.50 mL, 8.50 mmol). The reaction mixture was
stirred at 100 °C for 24 h. After cooling to rt, the solution was
neutralized with acetic acid, diluted with CH2Cl2, and washed
with water. The organic layer was then concentrated, and the
residue was purified by chromatography (4:1 hexane-EtOAc)
to yield 17 (2.03 g, 77%) as a colorless oil: Rf 0.21 (2:1
1
Rf 0.54 (4:1 hexane-EtOAc); [R]D þ120.4 (c 1.6, CHCl3); H
NMR (500 MHz, CDCl3, δH) 7.42-7.28 (m, 12 H, Ar),
7.12-7.10 (m, 2 H, Ar), 5.93-5.84 (m, 1 H, CH2dCH-CH2O),
5.53 (d, 1 H, J1,2 = 3.0 Hz, H-1), 5.30-5.24 (m, 1 H, CH2d
CH-CH2O), 5.20-5.16 (m, 1 H, CH2dCH-CH2O), 4.68-4.50
1
hexane-EtOAc); [R]D þ129.0 (c 0.6, CHCl3); H NMR (600
(m, 4 H, PhCH2O), 4.40-4.35 (m, 1 H, H-4), 4.13 (dd, 1 H, J1,2
=
MHz, CDCl3, δH) 7.34-7.27 (m, 5 H, Ar), 7.20-7.16 (m, 2 H,
Ar), 6.88-6.84 (m, 2 H, Ar), 4.90 (s, 1 H, H-1), 4.69 (d, 1 H, J=
12.3 Hz, PhCH2O), 4.54 (d, 1 H, J=11.4 Hz, PhCH2O), 4.52 (d,
1 H, J=12.3 Hz, PhCH2O), 4.40 (d, 1 H, J=11.4 Hz, PhCH2O),
4.27 (ddd, 1 H, J3,4=J4,5a=2.4 Hz, J4,5b=2.6 Hz, H-4), 4.11 (d,
1 H, J2,OH = 10.9 Hz, H-2), 3.83-3.80 (m, 4 H, H-3,
PMBOCH3), 3.63 (dd, 1 H, J4,5a = 2.4 Hz, J5a,5b = 10.4 Hz,
J
2,3 = 3.0 Hz, H-2), 4.06-3.98 (m, 3 H, CH2dCH-CH2O ꢀ 2,
H-3), 3.67 (dd, 1 H, J4,5a =3.9 Hz, J5a,5b=10.9 Hz, H-5a), 3.61
(dd, 1 H, J4,5b = 5.1 Hz, J5a,5b = 10.9 Hz, H-5b), 2.34 (s, 3 H,
tolyl CH3); 13C NMR (125 MHz, CDCl3, δC) 137.8 (Ar),
137.4(4) (Ar), 137.3(7) (Ar), 134.6 (Ar), 132.0 (Ar ꢀ 2), 131.0
(Ar), 129.7 (CH2dCH-CH2O), 128.4(4) (Arꢀ2), 128.4(0) (Arꢀ
2), 128.0 (Arꢀ2), 127.9 (Arꢀ2), 127.8(4) (Ar), 127.7(9) (Arꢀ2),
117.0 (CH2dCH-CH2O), 90.6 (C-1), 88.5 (C-2), 83.5 (C-3),
80.4 (C-4), 72.4 (PhCH2O), 72.3 (PhCH2O), 72.1 (CH2dCH-
H-5a), 3.44-3.40 (m, 4 H, H-5b, OCH3), 3.37 (d, 1 H, J2,OH
=
10.9 Hz, OH); 13C NMR (125 MHz, CDCl3, δC) 159.5 (Ar),
137.7 (Ar), 129.5 (Arꢀ2), 129.0 (Ar), 128.4 (Arꢀ2), 127.9 (Arꢀ2),
5002 J. Org. Chem. Vol. 75, No. 15, 2010

Liu et al.
JOCArticle
127.8 (Ar), 114.0 (Ar ꢀ 2), 110.6 (C-1), 85.0 (C-2), 83.7 (C-3),
77.8 (C-4), 73.4 (PhCH2O), 72.1 (PhCH2O), 69.4 (C-5), 55.3
(PMBOCH3, OCH3); ESIMS m/z calcd for [C21H26O6Na]þ
397.1622, found 397.1621.
3 H, PhCH2O), 4.50-4.44 (m, 3 H, PhCH2O, H-5Ca, H-5Ea),
4.40-4.32 (m, 4 H, H-2C, H-4C, H-5Cb, H-5Eb), 4.27 (ddd,
1 H, J3E,4E=J4E,5Eb=6.6 Hz, J4E,5Ea=4.5 Hz, H-4E), 4.25 (dd,
1 H, J2E,3E = J3E,4E = 6.6 Hz, H-3E), 4.14 (dd, 1 H, J1E,2E
4.5 Hz, J2E,3E = 6.6 Hz, H-2E), 4.08 (dd, 1 H, J2C,3C = 2.5 Hz,
3C,4C = 5.8 Hz, H-3C), 3.40 (s, 3 H, OCH3); 13C NMR (125
=
Methyl 2,3-anhydro-r-D-lyxofuranoside (20). Methyl R-D-ara-
binofuranoside 19 (2.69 g, 16.4 mmol) and triphenylphosphine
(5.16 g, 19.7 mmol) were dissolved in tetrahydrofuran (50 mL), and
the solution was cooled to 0 °C. Diisopropylazodicarboxylate (3.88
mL, 19.7 mmol) was added dropwise over a period of 10 min. After
complete addition of the reagent, the reaction mixture was warmed
to room temperature and was stirred for 1 h. The solution was
subsequently concentrated and purified by chromatography (4:1
hexane-EtOAc) to obtain 20 (2.16 g, 90%) as a white crystalline
solid: Rf 0.14 (2:1 hexane-EtOAc); [R]D þ97.1 (c 0.1, CHCl3); 1H
NMR (500 MHz, CDCl3, δH) 4.98 (s, 1 H, H-1), 4.17-4.13 (m,
J
MHz, CDCl3, δC) 166.3 (CdO), 166.1 (CdO), 137.7 (Ar), 137.6
(Ar), 137.5 (Ar), 133.7 (Ar), 133.1 (Ar), 133.0 (Ar), 130.2 (Ar),
129.9 (Arꢀ2), 129.8 (Arꢀ2), 129.7 (Ar ꢀ2), 128.5(5) (Arꢀ2),
128.4(7) (Ar), 128.4(4) (Ar), 128.3(5) (Arꢀ2), 128.3(4) (Arꢀ2),
128.3(0) (Ar ꢀ 2), 128.1(3) (Ar ꢀ 2), 128.0(7) (Ar), 127.8 (Ar),
127.7(1) (Arꢀ2), 127.6(9) (Ar), 107.1 (C-1C), 100.9 (C-1E), 86.3
(C-2C), 84.5 (C-3C), 83.9 (C-2E), 82.3 (C-3E), 80.2 (C-4C), 78.8
(C-4E), 72.8 (PhCH2O), 72.6(2) (PhCH2O), 72.5(7) (PhCH2O),
66.3 (C-5E), 64.4 (C-5C), 54.9 (OCH3); ESIMS m/z calcd for
[C46H46O11Na]þ 797.2932, found 797.2935.
1 H, H-4), 3.91-3.88 (m, 2 H, H-5a, H-5b), 3.75 (dd, 1 H, J1,2
=
Methyl 5-O-allyl-2,3-di-O-benzyl-β-D-arabinofuranosyl-(1f2)-
5-O-benzoyl-3-O-benzyl-r-D-arabinofuranoside (24): Isolated as
a colorless oil, 69%; Rf 0.60 (2:1 hexane-EtOAc); [R]D -5.4
(c 0.5, CHCl3); 1H NMR (500 MHz, CDCl3, δH) 8.07-8.04 (m,
2 H, Ar), 7.56-7.51 (m, 1 H, Ar), 7.42-7.38 (m, 2 H, Ar),
7.37-7.24 (m, 15 H, Ar), 5.82-5.74 (m, 1 H, CH2dCH-CH2O),
5.18-5.13 (m, 1 H, CH2dCH-CH2O), 5.10-5.04 (m, 2 H, CH2d
CH-CH2O, H-1E), 4.99 (s, 1 H, H-1C), 4.76-4.55 (m, 6 H,
PhCH2O), 4.49 (dd, 1 H, J4C,5Ca = 3.9 Hz, J5Ca,5Cb = 11.7 Hz,
H-5Ca), 4.42 (dd, 1 H, J4C,5Cb = 5.7 Hz, J5Ca,5Cb = 11.7 Hz,
H-5Cb), 4.37 (ddd, 1 H, J3C,4C=J4C,5Cb=5.7 Hz, J4C,5Ca=3.9
Hz, H-4C), 4.31 (dd, 1 H, J1C,2C = 1.1 Hz, J2C,3C = 2.6 Hz,
H-2C), 4.14-4.06 (m, 4 H, H-2E, H-3E, H-3C, H-4E),
3.91-3.82 (m, 2 H, CH2dCH-CH2O), 3.53-3.44 (m, 2 H,
H-5Ea, H-5Eb), 3.38 (s, 3 H, OCH3); 13C NMR (125 MHz,
CDCl3, δC) 166.3 (CdO), 138.2 (Ar), 137.7 (Ar), 137.6 (Ar),
134.4 (Ar), 133.0 (Ar), 129.9 (Ar), 129.8 (Arꢀ2), 129.5 (Arꢀ2),
129.3(7) (Ar ꢀ 3), 128.3(6) (Ar ꢀ 3), 128.1 (Ar), 128.0 (CH2d
CH-CH2O), 127.7(6) (Arꢀ3), 128.7(5) (Arꢀ3), 127.7(0) (Ar),
117.1 (CH2dCH-CH2O), 107.2 (C-1C), 100.5 (C-1E), 86.0
(C-2C), 84.2 (C-3C), 84.0 (C-2E), 82.8 (C-4C), 80.1 (C-3E),
80.0(C-4E), 72.6(PhCH2O), 72.4(4) (PhCH2O), 72.4(2) (PhCH2O),
72.1 (CH2dCH-CH2O), 71.9 (C-5E), 64.5 (C-5C), 54.9 (OCH3);
ESIMS m/z calcd for [C42H46O10Na]þ 733.2983, found 733.2986.
Methyl 2,3-di-O-benzyl-5-O-p-methoxybenzyl-β-D-arabino-
furanosyl-(1f2)-3-O-benzyl-5-O-p-methoxybenzyl-r-D-arabinofur-
anoside (25): Isolated as a colorless oil, 79%; Rf 0.28 (3:1 hexane-
EtOAc); [R]D -22.7 (c 0.5, CHCl3); NMR (600 MHz, CDCl3, δH)
7.36-7.01 (m, 17 H, Ar), 7.16-7.12 (m, 2 H, Ar), 6.87-6.84 (m,
2 H, Ar), 6.82-6.78 (m, 2 H, Ar), 5.07 (d, 1 H, J1E,2E = 4.2 Hz,
H-1E), 4.90 (s, 1 H, H-1C), 4.68-4.64 (m, 2 H, PhCH2O),
4.62-4.55 (m, 3 H, PhCH2O), 4.48-4.44 (m, 3 H, PhCH2O),
4.38-4.30 (m, 2 H, PhCH2O), 4.26 (dd, 1 H, J1C,2 C = 1.3 Hz,
0.7 Hz, J2,3=2.9 Hz, H-2), 3.66 (d, 1 H, J2,3=2.9 Hz, H-3), 3.43 (s,
3 H, OCH3); 13C NMR (125 MHz, CDCl3, δC) 102.2 (C-1), 76.2
(C-4), 61.9 (C-5), 55.8 (C-3), 55.6 (OCH3), 54.1 (C-2); ESIMS m/z
calcd for [C6H10O4Na]þ 169.0471, found 169.0472.
Methyl 3-O-benzyl-r-D-arabinofuranoside (21). To a solution
of compound 20 (0.72 g, 2.71 mmol) dissolved in benzyl alcohol
(4 mL) was added 1 M BnONa in benzyl alcohol (4.10 mL, 4.10
mmol). The reaction mixture was stirred at 100 °C for 24 h. After
cooling to rt, the solution was neutralized with acetic acid,
diluted with CH2Cl2, and washed with water. The organic layer
was then concentrated, and the residue was purified by chro-
matography (4:1 hexane-EtOAc) to yield 21 (0.55 g, 80%) as a
colorless syrup: Rf 0.38 (2:1 hexane-EtOAc); [R]D þ149.4 (c 0.3,
CHCl3); 1H NMR (600 MHz, CD3OD, δH) 7.35-7.30 (m, 4 H,
Ar), 7.26-7.24 (m, 1 H, Ar), 4.79 (s, 1 H, H-1), 4.67 (d, 1 H, J=
11.9 Hz, PhCH2O), 4.55 (d, 1 H, J = 11.9 Hz, PhCH2O), 4.12
(dd, 1 H, J1,2=1.1 Hz, J2,3=2.6 Hz, H-2), 4.03 (ddd, 1 H, J3,4
5.9 Hz, J4,5a=3.6 Hz, J4,5b=5.6 Hz, H-4), 3.76 (ddd, 1 H, J1,3
0.6 Hz, J2,3 =2.6 Hz, J3,4 =5.9 Hz, H-3), 3.69 (dd, 1 H, J4,5a
=
=
=
3.6 Hz, J5a,5b = 11.9 Hz, H-5a), 3.61 (dd, 1 H, J4,5b = 5.6 Hz,
J
5a,5b = 11.9 Hz, H-5b), 3.38 (s, 3 H, OCH3); 13C NMR (125
MHz, CD3OD, δC) 139.5 (Ar), 129.4 (Ar ꢀ 2), 128.9 (Ar ꢀ 2),
128.8 (Ar), 111.1 (C-1), 86.8 (C-2), 84.5 (C-3), 81.5 (C-4), 73.1
(PhCH2O), 63.3 (C-5), 55.1 (OCH3); ESIMS m/z calcd for
[C13H18O5Na]þ 277.1047, found 277.1046.
Methyl 2,3-anhydro-5-O-p-methoxybenzyl-r-D-lyxofuranoside
(22). To a solution of compound 20 (1.29 g, 8.86 mmol) in
DMF (15 mL) were added NaH (425 mg, 10.6 mmol, 60%
dispersion in oil) and PMBCl (1.48 mL, 10.6 mmol) at 0 °C. The
mixture was stirred at this temperature for 1 h, and the reaction
was then quenched by the addition of CH3OH. The solution was
diluted with EtOAc and washed with water. The organic layer
was dried (MgSO4) and concentrated, and the residue was
purified by chromatography (6:1 hexane-EtOAc) to afford 22
(1.88 g, 80%) as a colorless oil: Rf 0.25 (6:1 hexane-EtOAc);
J2C,3C=2.9 Hz, H-2C), 4.23 (ddd, 1 H, J3C,4C=J4C,5Cb=6.0 Hz,
4C,5Ca =4.3 Hz, H-4C), 4.12-4.06 (m, 3 H, H-2E, H-3E, H-4E),
J
1
[R]D þ21.8 (c 0.7, CHCl3); H NMR (500 MHz, CDCl3, δH)
3.99 (dd, 1 H, J2C,3C=2.9 Hz, J3C,4C=6.0 Hz, H-3C), 3.78 (s, 3 H,
PMBOCH3), 3.76 (s, 3 H, PMBOCH3), 3.58-3.48 (m, 4 H,
H-5Ca, H-5Cb, H-5Ea, H-5Eb), 3.38 (s, 3 H, OCH3); 13C NMR
(125 MHz, CDCl3, δC) 159.1(9) (Ar), 159.1(6) (Ar), 138.2 (Ar),
138.1 (Ar), 137.7 (Ar), 130.3 (Ar), 130.1 (Ar), 129.4 (Arꢀ2), 129.2
(Ar ꢀ 2), 128.5 (Ar ꢀ 2), 128.3(2) (Ar ꢀ 2), 129.2(6) (Ar ꢀ 2),
127.9(7) (Arꢀ2), 127.9(0) (Ar), 127.7(4) (Arꢀ2), 127.7(0) (Arꢀ2),
127.6(2) (Ar), 127.5(6) (Ar), 113.7 (Ar ꢀ 4), 107.0 (C-1C), 100.3
(C-1E), 86.0 (C-2C), 84.0 (C-2E, C-3C), 83.1 (C-3E), 81.4 (C-4C),
80.1 (C-4E), 73.0 (PhCH2O), 72.8 (PhCH2O), 72.5 (PhCH2O),
72.4 (PhCH2O), 72.2 (PhCH2O), 71.8 (C-5E), 69.8 (C-5C), 55.2(3)
(PMBOCH3), 55.2(2) (PMBOCH3), 54.9 (OCH3); ESIMS m/z
calcd for [C48H54O11Na]þ 829.3558, found 829.3558.
7.30-7.26 (m, 2 H, Ar), 6.91-6.87 (m, 2 H, Ar), 4.95 (s, 1 H,
H-1), 4.55 (d, 1 H, J=11.7 Hz, PhCH2O), 4.51 (d, 1 H, J=11.7
Hz, PhCH2O), 4.18 (dd, 1 H, J4,5a=J4,5b=6.3 Hz, H-4), 3.81 (s,
3 H, PMBOCH3), 3.75 (d, 1 H, J2,3 = 2.3 Hz, H-2), 3.65-3.61
(m, 2 H, H-3, H-5), 3.42 (s, 3 H, OCH3); 13C NMR (125 MHz,
CDCl3, δC) 159.3 (Ar), 130.0 (Ar), 129.4 (Arꢀ2), 113.8 (Arꢀ2),
102.3 (C-1), 76.8 (C-4), 73.3 (PhCH2O), 68.2 (C-5), 56.2 (C-3),
55.6 (OCH3), 55.3 (PMBOCH3), 54.4 (C-2); ESIMS m/z calcd
for [C14H18O5Na]þ 289.1047, found 289.1048.
Methyl 5-O-benzoyl-2,3-di-O-benzyl-β-D-arabinofuranosyl-(1f2)-
5-O-benzoyl-3-O-benzyl-r-D-arabinofuranoside (23): Isolated as
a colorless oil, 23%; Rf 0.35 (3:1 hexane-EtOAc); [R]D þ4.0
(c 1.0, CHCl3); 1H NMR (600 MHz, CDCl3, δH) 8.05-8.02 (m,
2 H, Ar), 7.98-7.95 (m, 2 H, Ar), 7.54-7.50 (m, 2 H, Ar),
7.40-7.18 (m, 19 H, Ar), 5.11 (d, 1 H, J1E,2E = 4.5 Hz, H-1E),
4.90 (s, 1 H, H-1C), 4.75-4.68 (m, 2 H, PhCH2O), 4.64-4.58 (m,
Methyl 5-O-benzoyl-2,3-di-O-benzyl-β-D-arabinofuranosyl-(1f2)-
3-O-benzyl-5-O-p-methoxybenzyl-r-D-arabinofuranoside (26):
Isolated as a colorless oil, 76%; Rf 0.40 (3:1 hexane-EtOAc);
1
[R]D -11.6 (c 2.0, CHCl3); H NMR (500 MHz, CDCl3, δH)
J. Org. Chem. Vol. 75, No. 15, 2010 5003

Liu et al.
JOCArticle
8.02-7.98 (m, 2 H, Ar), 7.56-7.52 (m, 2 H, Ar), 7.40-7.26
(m, 12 H, Ar), 7.24-7.20 (m, 6 H, Ar), 6.84-6.82 (m, 2 H, Ar),
5.14 (d, 1 H, J1E,2E = 4.4 Hz, H-1E), 4.93 (s, 1 H, H-1C), 4.73
(d, 1 H, J=11.6 Hz, PhCH2O), 4.67-4.55 (m, 4 H, PhCH2O),
of the disaccharide mixture of 27 (1.45 g, 2.01 mmol) in CH3OH
(50 mL) and CH2Cl2 (6 mL) was added PdCl2 (71 mg, 0.40 mmol).
The solution was stirred for 12 h, the reaction was quenched by
the addition of triethylamine, and the mixture was concentrated.
Chromatography of the residue (8:1 hexane-EtOAc) gave 29
(1.02 g, 74%) as a colorless syrup: Rf 0.32 (2:1 hexane-EtOAc);
4.48-4.42 (m, 4 H, PhCH2O, H-5Eb), 4.33 (dd, 1 H, J4E,5Ea
6.9 Hz, J5Ea,5Eb = 11.4 Hz, H-5Ea), 4.28-4.24 (m, 2 H, H-2C,
H-4E), 4.23-4.17 (m, 2 H, H-4C, H-3E), 4.12 (dd, 1 H, J1E,2E
4.4 Hz, J2E,3E = 6.9 Hz, H-2E), 3.98 (dd, 1 H, J2C,3C = 2.6 Hz,
3C,4C=6.0 Hz, H-3C), 3.77 (s, 3 H, PMBOCH3), 3.56-3.50 (m,
=
1
=
[R]D -23.5 (c 0.4, CHCl3); H NMR (500 MHz, CDCl3, δH)
7.38-7.24 (m, 17 H, Ar), 6.89-6.86 (m, 2 H, Ar), 5.05 (d, 1 H,
J1E,2E=4.5 Hz, H-1E), 4.90 (d, 1 H, J1C,2C=1.6 Hz, H-1C), 4.74
J
2 H, H-5Ca, H-5Cb), 3.39 (s, 3 H, OCH3); 13C NMR (125 MHz,
CDCl3, δC) 166.1 (CdO), 159.2 (Ar), 137.9 (Ar), 137.8 (Ar),
137.6 (Ar), 133.1 (Arꢀ2), 130.2 (Ar), 129.8 (Ar), 129.7 (Arꢀ2),
129.4 (Arꢀ2), 128.5 (Arꢀ2), 128.4(1) (Arꢀ2), 128.3(7) (Arꢀ2),
128.2 (Ar ꢀ 2), 128.0 (Ar ꢀ 3), 127.8 (Ar), 127.7 (Ar ꢀ 3), 127.5
(Ar), 113.7(3) (Ar), 113.7(0) (Ar), 107.0 (C-1C), 100.9 (C-1E),
86.8 (C-2C), 84.3 (C-3C), 83.9 (C-2E), 82.5 (C-3E), 81.6 (C-4C),
78.8 (C-4E), 72.9 (PhCH2O), 72.6 (PhCH2Oꢀ2), 72.4 (PhCH2O),
69.8 (C-5C), 66.3 (C-5E), 55.2 (PMBOCH3), 54.9 (OCH3);
ESIMS m/z calcd for [C47H50O11Na]þ 813.3245, found 813.3237.
Methyl 5-O-allyl-2,3-di-O-benzyl-β-D-arabinofuranosyl-(1f2)-
3-O-benzyl-5-O-p-methoxybenzyl-r-D-arabinofuranoside (27):
Isolated as a colorless oil, 80%; Rf 0.38 (3:1 hexane-EtOAc);
(d, 1 H, J=11.6 Hz, PhCH2O), 4.66-4.56 (m, 4 H, PhCH2O),
4.52-4.44 (m, 3 H, PhCH2O), 4.28 (dd, 1 H, J2E,3E = 7.1 Hz,
J
3E,4E =6.5 Hz, H-3E), 4.23 (dd, 1 H, J1C,2C =1.6 Hz, J2C,3C
3.5 Hz, H-2C), 4.18 (ddd, 1 H, J3C,4C=6.3 Hz, J4C,5Ca=4.0 Hz,
4C,5Cb =5.0 Hz, H-4C), 4.12-4.07 (m, 2 H, H-2E, H-3C), 3.99
=
J
(ddd, 1 H, J3E,4E = 6.4 Hz, J4E,5Ea = 3.0 Hz, J4E,5Eb = 4.8 Hz,
H-4E), 3.80 (s, 3 H, PMBOCH3), 3.66-3.50 (m, 4 H, H-5Ea,
H-5Ca, H-5Eb, H-5Cb), 3.38 (s, 3 H, OCH3), 2.29 (dd, 1 H,
J
5Ea,OH=5.0 Hz, J5Eb,OH=7.9 Hz, OH); 13C NMR (125 MHz,
CDCl3, δC) 159.3 (Ar), 138.7 (Ar), 137.8 (Ar), 137.6 (Ar), 130.0
(Ar), 129.5 (Arꢀ2), 128.5 (Arꢀ2), 128.4 (Arꢀ2), 128.3 (Arꢀ2),
128.0 (Arꢀ2), 127.7(9) (Arꢀ2), 127.7(8) (Arꢀ2), 127.7(3) (Ar),
127.7(0) (Arꢀ2), 113.8 (Arꢀ2), 107.0 (C-1C), 100.4 (C-1E), 86.6
(C-2C), 84.2 (C-2E), 83.2 (C-3C), 82.0 (C-4E), 81.0 (C-4C), 80.6
(C-3E), 73.0 (PhCH2O), 72.7 (PhCH2O), 72.6 (PhCH2O), 72.2
(PhCH2O), 69.3 (C-5C), 63.4 (C-5E), 55.3 (PMBOCH3), 55.1
(OCH3); ESIMS m/z calcd for [C40H46O10Na]þ 709.2983, found
709.2982.
1
[R]D -22.7 (c 0.8, CHCl3); H NMR (600 MHz, CDCl3, δH)
7.36-7.23 (m, 17 H, Ar), 6.87-6.84 (m, 2 H, Ar), 5.84-5.76 (m,
1 H, CH2dCH-CH2O), 5.20-5.15 (m, 1 H, CH2dCH-CH2O),
5.11-5.08 (m, 1 H, CH2dCH-CH2O), 5.05 (d, 1 H, J1E,2E=3.7
Hz, H-1E), 4.89 (s, 1 H, H-1C), 4.70-4.55 (m, 5 H, PhCH2O),
4.51-4.47 (m, 3 H, PhCH2O), 4.26 (dd, 1 H, J1C,2C = 1.2 Hz,
Methyl 2,3-di-O-benzyl-β-D-arabinofuranosyl-(1f2)-3-O-benzyl-
r-D-arabinofuranoside (30). To a solution of compound 29 (0.85 g,
1.24 mmol) in CH2Cl2 (6 mL) was added trifluoroacetic acid
(0.82 mL). The reaction mixture was allowed to stir for 10 min,
and the reaction was then quenched by the addition of triethyl-
amine and the solution concentrated. The residue was purified by
chromotography to give 30 (0.61 g, 87%) as a colorless syrup: Rf 0.57
J2C,3C =2.9 Hz, H-2C), 4.20 (ddd, 1 H, J3C,4C =6.0 Hz, J4C,5Ca =
J4C,5Cb = 4.2 Hz, H-4C), 4.10-4.05 (m, 3 H, H-2E, H-3E,
H-4E), 3.98 (dd, 1 H, J2C,3C = 2.9 Hz, J3C,4C = 6.0 Hz, H-3C),
3.91-3.82 (m, 2 H, CH2dCH-CH2O), 3.79 (s, 3 H, PMBOCH3),
3.59-3.53 (m, 2 H, H-5Ca, H-5Ea), 3.51-3.45 (m, 2 H, H-5Cb,
H-5Eb), 3.38 (s, 3 H, OCH3); 13C NMR (125 MHz, CDCl3, δC)
159.2 (Ar), 138.2 (Ar), 138.1 (Ar), 137.7 (Ar), 134.6 (Ar), 130.2
(Ar), 129.4 (Arꢀ3), 128.5 (Arꢀ2), 128.4 (Arꢀ2), 128.3 (Arꢀ2),
128.0 (CH2dCH-CH2O), 127.9 (Ar), 127.7(5) (Arꢀ4), 127.6(8)
(Ar), 127.5(9) (Ar), 116.9 (CH2dCH-CH2O), 113.7 (Ar ꢀ 2),
107.0 (C-1C), 100.3 (C-1E), 86.0 (C-2C), 84.0(4) (C-2E), 84.0(2)
(C-3C), 83.1 (C-3E), 81.3 (C-4C), 80.1 (C-4E), 73.0 (PhCH2O),
72.5 (PhCH2O), 72.4 (PhCH2O), 72.2 (PhCH2O), 72.1(2) (CH2d
CH-CH2O), 72.0(8) (C-5E), 69.8 (C-5C), 55.3 (PMBOCH3),
54.9 (OCH3); ESIMS m/z calcd for [C43H50O10Na]þ 749.3296,
found 749.3292.
Methyl 2,3-di-O-benzyl-5-O-tert-butyldimethylsilyl-β-D-arabino-
furanosyl-(1f2)-3-O-benzyl-5-O-p-methoxybenzyl-r-D-arabino-
furanoside (28):Isolated as a colorless oil, 61%; Rf 0.33 (4:1 hexane-
EtOAc); [R]D -24.6 (c 0.5, CHCl3); 1H NMR (500 MHz, CDCl3,
δH) 7.38-7.24 (m, 17 H, Ar), 6.89-6.86 (m, 2 H, Ar), 5.08 (d, 1 H,
J1E,2E = 3.8 Hz, H-1E), 4.93 (s, 1 H, H-1C), 4.73-4.55 (m, 5 H,
PhCH2O), 4.52-4.48 (m, 3 H, PhCH2O), 4.28-4.25 (m, 1 H,
H-2C), 4.24-4.20 (m, 1 H, H-4C), 4.12-4.07 (m, 2 H, H-4E,
H-2E), 4.02-3.96 (m, 2 H, H-3E, H-3C), 3.80 (s, 3 H, PMBOCH3),
3.76-3.66 (m, 2 H, H-5Ea, H-5Eb), 3.60-3.54 (m, 2 H, H-5Ca,
H-5Cb), 3.40 (s, 3 H, OCH3), 0.90-0.87 (m, 9 H, t-butyl CH3ꢀ3),
0.05-0.02 (m, 6 H, TBDMS CH3 ꢀ 2); 13C NMR (125 MHz,
CDCl3, δC) 159.2 (Ar), 138.3 (Ar), 138.0 (Ar), 137.8 (Ar), 130.2
(Arꢀ2), 129.4 (Arꢀ2), 128.4(4) (Arꢀ2), 128.3(5) (Arꢀ2), 128.2(9)
(Arꢀ2), 128.0 (Arꢀ2), 127.8(7) (Ar), 127.7 (Arꢀ2), 127.6(7) (Arꢀ
2), 127.6(2) (Ar), 113.7 (Arꢀ 2), 107.0 (C-1C), 100.5 (C-1E), 86.2
(C-2C), 84.1(8) (C-3C), 84.1(6) (C-2E), 84.1(1) (C-4E), 82.2 (C-3E),
81.3 (C-4C), 73.0 (PhCH2O), 72.5 (PhCH2O), 72.3(3) (PhCH2O),
72.3(0) (PhCH2O), 69.8 (C-5C), 65.4 (C-5E), 55.3 (PMBOCH3),
54.9 (OCH3), 25.9 (t-butyl CH3 ꢀ 3), 18.3 (t-butyl C), -5.2(5) (Si
CH3), -5.3(0) (Si CH3); ESIMS m/z calcd for [C46H60O10SiNa]þ
823.3848, found 823.3852.
1
(1:1 hexane-EtOAc); [R]D -0.5 (c 0.4, CHCl3); H NMR (600
MHz, CDCl3, δH) 7.39-7.28 (m, 15 H, Ar), 5.00 (d, 1 H, J1E,2E
=
4.6 Hz, H-1E), 4.87 (s, 1 H, H-1C), 4.74-4.68 (m, 2 H, PhCH2O),
4.63-4.54 (m, 4 H, PhCH2O), 4.27-4.23 (m, 1 H, H-2E), 4.19 (dd,
1 H, J2C,3C =2.4 Hz, J3E,4E =5.6 Hz, H-3C), 4.17-4.16 (m, 1 H,
H-2C), 4.14-4.11 (m, 1 H, H-4C), 4.09 (dd, 1 H, J2E,3E =7.2 Hz,
J3E,4E =4.7 Hz, H-3E), 3.98 (ddd, 1 H, J3E,4E =4.7 Hz, J4E,5Ea
=
2.9 Hz, J4E,5Eb =6.5 Hz, H-4E), 3.81 (dd, 1 H, J4C,5Ca =2.9 Hz,
J5Ca,5Cb = 12.2 Hz, H-5Ca), 3.67 (dd, 1 H, J4E,5Ea = 2.9 Hz,
J5Ea,5Eb = 12.3 Hz, H-5Ea), 3.58-3.53 (m, 2 H, H-5Eb, H-5Cb),
3.38 (s, 3 H, OCH3); 13C NMR (125 MHz, CDCl3, δC) 138.0 (Ar),
137.8 (Ar), 137.5 (Ar), 128.6 (Arꢀ2), 128.4 (Arꢀ4), 128.0(9) (Ar),
128.0(5) (Ar ꢀ 2), 127.9(1) (Ar), 127.8(4) (Ar ꢀ 2), 127.8(2) (Ar),
127.7 (Ar ꢀ 2), 107.4 (C-1C), 100.8 (C-1C), 87.0 (C-2C), 84.2
(C-3E), 83.1 (C-4C), 82.5 (C-3C), 82.0 (C-4E), 80.4 (C-2E), 72.8
(PhCH2O ꢀ 2), 72.4 (PhCH2O), 63.2 (C-5C), 62.1 (C-5E), 54.9
(OCH3); ESIMS m/z calcd for [C32H38O9Na]þ 589.2408, found
589.2411.
Methyl 2,3-di-O-benzoyl-5-O-tert-butyldiphenylsilyl-r-D-arabino-
furanosyl-(1f3)-[2,3-di-O-benzoyl-5-O-tert-butyldiphenylsilyl-
r-D-arabinofuranosyl-(1f5)]-2-O-benzyl-r-D-arabinofuranoside
(33). The donor 31 (1.80 g, 2.57 mmol) and acceptor 32 (272 mg,
1.07 mmol) were dried under vacuum in the presence of P2O5 for
˚
2 h. To this mixture were added CH2Cl2 (15 mL) and 4 A mole-
cular sieves (2.0 g). The solution was allowed to stir at room
temperature for 30 min and cooled to -60 °C, followed by the
addition of N-iodosuccinimide (627 mg, 2.79 mmol) and silver
triflate (110 mg, 0.43 mmol). After the solution turned into red/
dark brown, triethylamine was added. The reaction mixture was
then diluted with CH2Cl2 and filtered through Celite. The fil-
trate was concentrated, and the resulting syrup was purified by
chromatography (4:1 hexane-EtOAc) to give 33 (1.32 g, 88%)
as a colorless syrup: Rf 0.44 (3:1 hexane-EtOAc); [R]D þ12.9
(c2.0, CHCl3);1H NMR (600 MHz, CDCl3,δH) 8.06-8.01 (m, 4 H,
Methyl 2,3-di-O-benzyl-β-D-arabinofuranosyl-(1f2)-3-O-benzyl-
5-O-p-methoxybenzyl-r-D-arabinofuranoside (29). To a solution
5004 J. Org. Chem. Vol. 75, No. 15, 2010

Liu et al.
JOCArticle
Ar), 7.95-7.92 (m, 4 H, Ar), 7.70-7.65 (m, 8 H, Ar), 7.58-7.53
(m, 2 H, Ar), 7.51-7.48 (m, 24 H, Ar), 7.22-7.18 (m, 2 H, Ar),
7.16-7.14 (m, 1 H, Ar), 5.65-5.64 (m, 1 H, H-3D), 5.63-5.61
(m, 1 H, H-3C), 5.53 (d, 1 H, J1D,2D = 1.4 Hz, H-2D), 5.43 (d,
1 H, J1C,2C=1.7 Hz, H-2C), 5.27 (s, 2 H, H-1C, H-1D), 4.94 (d,
1 H, J1B,2B=1.6 Hz, H-1B), 4.62-4.57 (m, 2 H, PhCH2O), 4.44
(ddd, 1 H, J3D,4D=J4D,5 Da=4.4 Hz, J5 Da,5Db=4.6 Hz, H-4D),
4.36 (ddd, 1 H, J3C,4C = 3.8 Hz, J4C,5Ca = J5Ca,5Cb = 4.7 Hz,
H-4C), 4.27-4.23 (m, 2 H, H-4B, H-3B), 4.10-4.08 (m, 1 H,
H-2B), 4.03-3.90 (m, 5 H, H-5Ba, H-5Ca, H-5Cb, H-5 Da,
H-5Db), 3.85-3.82 (m, 1 H, H-5Bb), 3.35 (s, 3 H, OCH3),
1.04-0.98 (s, 18 H, t-butyl CH3);13CNMR(125MHz, CDCl3, δC)
165.6 (CdO), 165.5 (CdO), 165.2(2) (CdO), 165.2(0) (CdO),
137.5 (Ar), 135.7 (Ar), 135.6(3) (Ar ꢀ 2), 135.6(2) (Ar ꢀ 2),
135.6(0) (Ar ꢀ 2), 135.5 (Ar ꢀ 2), 133.4 (Ar), 133.3(3) (Ar),
133.3(1) (Ar), 133.2(8) (Ar), 133.2(4) (Ar), 133.1(9) (Ar),
133.1(6) (Ar), 133.1(4) (Ar), 133.1(1) (Ar), 129.9(5) (Ar ꢀ 2),
129.9(3) (Arꢀ2), 129.9(1) (Arꢀ2), 129.8(6) (Arꢀ2), 129.7 (Arꢀ
2), 129.6(1) (Ar ꢀ 2), 129.5(7) (Ar), 129.4(5) (Ar), 129.3 (Ar),
129.2 (Ar), 128.4(8) (Arꢀ2), 128.4(6) (Arꢀ2), 128.3(9) (Arꢀ2),
128.3(6) (Arꢀ2), 128.3(2) (Arꢀ2), 128.2(8) (Arꢀ2), 127.9 (Arꢀ
2), 127.7 (Ar ꢀ 2), 127.6 (Ar ꢀ 3), 107.2 (C-1B), 105.8 (C-1D),
105.4 (C-1C), 88.3 (C-2B), 83.5 (C-4C), 83.2 (C-4D), 82.3 (C-2D,
C-2C), 81.2 (C-3B), 80.0 (C-4B), 77.3 (C-3D, C-3C), 72.0
(PhCH2O), 66.6 (C-5B), 63.4 (C-5C), 63.3 (C-5D), 54.9 (OCH3),
26.8 (t-butyl CH3), 19.3(0) (t-butyl C), 19.2(6) (t-butyl C); ESIMS
m/z calcd for [C83H86O17Si2Na]þ 1433.5296, found 1433.5298.
Methyl 2,3-di-O-benzyl-r-D-arabinofuranosyl-(1f3)-[2,3-di-
O-benzyl-r-D-arabinofuranosyl-(1f5)]-2-O-benzyl-r-D-arabino-
furanoside (34). To a solution of compound 33 (1.32 g, 0.94
mmol) in 1:1 CH3OH-CH2Cl2 (8 mL) was added a 1 M solution
of NaOCH3 in CH3OH until a pH of 11 was obtained. The reac-
tion was stirred at room temperature for 2 h, neutralized by the
addition of AcOH, and concentrated. The residue was dissolved
in DMF (20 mL) and THF (3 mL), and then the solution was
cooled to 0 °C. NaH 60% in mineral oil (203 mg, 5.08 mmol) and
BnBr (0.52 mL, 4.40 mmol) were subquently added to the
solution. The reaction was allowed to stir for 2 h and then quen-
ched by the addition of CH3OH. The solution was diluted with
EtOAc and washed with water. The organic layer was dried
(MgSO4), filtered, and concentrated. The residue was dissolved
in THF (10 mL), and then TBAF (2.00 mL, 1 M in THF) was
added. The reaction was stirred overnight and concentrated.
Chromatography of the residue (1:1 hexane-EtOAc) gave 3
(613 mg, 74% over three steps) as a colorless syrup: Rf 0.29 (1:1
hexane-EtOAc); [R]D þ84.8 (c 0.3, CHCl3); 1H NMR (500
MHz, CDCl3, δH) 7.40-7.20 (m, 25 H, Ar), 5.17 (s, 1 H, H-1D),
5.13 (d, 1 H, J1C,2C = 1.5 Hz, H-1C), 4.96 (d, 1 H, J1B,2B = 1.5
Hz, H-1B), 4.62-4.47 (m, 9 H, PhCH2O), 4.39 (d, 1 H, J=11.8
Hz, PhCH2O), 4.32 (dd, 1 H, J2B,3B = 3.8 Hz, J3B,4B = 7.4 Hz,
H-3B), 4.26 (ddd, 1 H, J3D,4D = 2.9 Hz, J4D,5 Da = 5.2 Hz,
J4D,5Db = 6.5 Hz, H-4D), 4.16-4.08 (m, 3 H, H-2D, H-4B,
H-4C), 4.04 (dd, 1 H, J1C,2C = 1.5 Hz, J2C,3C = 3.8 Hz, H-2C),
4.02 (dd, 1 H, J1B,2B=1.5 Hz, J2B,3B =3.8 Hz, H-2B), 3.96 (dd,
1 H, J4B,5Ba=3.9 Hz, J5Ba,5Bb=11.6 Hz, H-5Ba), 3.92 (dd, 1 H,
(PhCH2O), 71.9(4) (PhCH2O), 65.0 (C-5B), 62.8 (C-5D), 62.7
(C-5C), 55.0 (OCH3); ESIMS m/z calcd for [C51H58O13Na]þ
901.3770, found 901.3764.
Methyl 2,3-di-O-benzyl-5-O-butyryl-β-D-arabinofuranosyl-(1f2)-
3-O-benzyl-5-O-butyryl-r-D-arabinofuranoside (35): Isolated as
a colorless oil, 96%; Rf 0.68 (1:1 hexane-EtOAc); [R]D -3.7
(c 0.2, CHCl3); 1H NMR (600 MHz, CDCl3, δH) 7.38-7.26 (m,
15 H, Ar), 5.07 (d, 1 H, J1E,2E = 3.5 Hz, H-1E), 4.86 (s, 1 H,
H-1C), 4.75-4.70 (m, 2 H, PhCH2O), 4.64-4.50 (m, 4 H,
PhCH2O), 4.30-4.20 (m, 4 H, H-2E, H-5Ea, H-5Ca, H-4E),
4.18-4.13 (m, 3 H, H-5Eb, H-5Cb, H-3C), 4.11-4.08 (m, 2 H,
H-2C, H-4C), 3.96 (dd, 1 H, J2E,3E = 2.7 Hz, J3E,4E = 6.1 Hz,
H-3E), 3.40 (s, 3 H, OCH3), 2.32-2.26 (m, 2 H, acyl CH2),
2.24-2.20 (m, 2 H, acyl CH2), 1.68-1.56 (m, 4 H, acyl CH2ꢀ2),
0.96-0.87 (m, 6 H, acyl CH3ꢀ2); 13C NMR (125 MHz, CDCl3,
δC) 173.3 (CdO), 173.2 (CdO), 137.8 (Ar), 137.7 (Ar), 137.5
(Ar), 128.5(4) (Arꢀ2), 128.4(5) (Arꢀ2), 128.3(9) (Arꢀ2), 128.1
(Ar), 128.0 (Arꢀ2), 127.9 (Ar), 127.8(0) (Ar), 127.7(7) (Arꢀ2),
127.7(1) (Arꢀ2), 107.0 (C-1C), 100.7 (C-1E), 86.1 (C-2E), 84.1
(C-2C), 83.8 (C-3E), 82.4 (C-4C), 80.0 (C-4E), 78.9 (C-3C), 72.7
(PhCH2O), 72.5 (PhCH2O), 72.4 (PhCH2O), 65.8 (C-5C), 63.7
(C-5E), 54.9 (OCH3), 35.9(3) (acyl CH2), 35.8(9) (acyl CH2),
18.3(4) (acyl CH2), 18.3(0) (acyl CH2), 13.6(4) (acyl CH3), 13.6(0)
(acyl CH3); ESIMS m/z calcd for [C40H50O11Na]þ 729.3245,
found 729.3247.
Methyl 2,3-di-O-benzyl-5-O-decanoyl-β-D-arabinofuranosyl-
(1f2)-3-O-benzyl-5-O-decanoyl-r-D-arabinofuranoside (36):
Isolated as a colorless oil, 90%; Rf 0.48 (2:1 hexane-EtOAc);
[R]D -3.2 (c 0.4, CHCl3); 1H NMR (600 MHz, CDCl3, δH)
7.38-7.26 (m, 15 H, Ar), 5.07 (d, 1 H, J1E,2E = 3.7 Hz, H-1E),
4.87 (s, 1 H, H-1C), 4.74-4.70 (m, 2 H, PhCH2O), 4.64-4.56 (m,
3 H, PhCH2O), 4.52 (d, 1 H, J = 11.8 Hz, PhCH2O), 4.29 (dd,
1 H, J1C,2C = 1.2 Hz, J2C,3C = 2.9 Hz, H-2C), 4.27 (dd, 1 H,
J
4E,5Ea =3.7 Hz, J5Ea,5Eb =3.7 Hz, H-5Ea), 4.25-4.20 (m, 2 H,
H-5Ca, H-4E), 4.17-4.12 (m, 3 H, H-5Eb, H-5Cb, H-3C),
4.11-4.08 (m, 2 H, H-2E, H-4C), 3.95 (dd, 1 H, J2E,3E = 2.9
Hz, J3E,4E =6.2 Hz, H-3E), 3.38 (s, 3 H, OCH3), 2.34-2.27 (m,
2 H, acyl CH2), 2.26-2.18 (m, 2 H, acyl CH2), 1.64-1.50 (m,
4 H, acyl CH2 ꢀ2), 1.34-1.20 (m, 24 H, acyl CH2 ꢀ12), 0.92-
0.86 (m, 6 H, acyl CH3 ꢀ 2); 13C NMR (125 MHz, CDCl3, δC)
173.5 (CdO), 173.3 (CdO), 137.8 (Ar), 137.7 (Ar), 137.5 (Ar),
128.5(4) (Arꢀ2), 128.4(5) (Arꢀ2), 128.3(8) (Arꢀ2), 128.1 (Ar),
128.0 (Ar ꢀ 2), 127.9 (Ar), 127.7(9) (Ar), 127.7(7) (Ar ꢀ 2),
127.6(9) (Arꢀ2), 107.0 (C-1C), 100.7 (C-1E), 86.1 (C-2E), 84.1
(C-2C), 83.8 (C-3E), 82.5 (C-4C), 80.0 (C-4E), 78.9 (C-3C), 72.7
(PhCH2O), 72.5 (PhCH2O), 72.4 (PhCH2O), 65.9 (C-5C), 63.8
(C-5E), 54.9 (OCH3), 34.1 (acyl CH2), 31.8(7) (acyl CH2), 31.8(5)
(acyl CH2), 29.4(5) (acyl CH2), 29.4(1) (acyl CH2), 29.3(0) (acyl
CH2), 29.2(8) (acyl CH2), 29.2(5) (acyl CH2), 29.1(5) (acyl CH2),
29.1(4) (acyl CH2), 24.8(7) (acyl CH2), 24.8(3) (acyl CH2), 22.7
(acyl CH2), 14.1 (acyl CH3 ꢀ 2); ESIMS m/z calcd for [C52H74-
O11Na]þ 897.5127, found 897.5122.
Methyl 2,3-di-O-benzyl-5-O-palmitoyl-β-D-arabinofuranosyl-
(1f2)-3-O-benzyl-5-O-palmitoyl-r-D-arabinofuranoside (37):
Isolated as a colorless oil, 82%; Rf 0.56 (4:1 hexane-EtOAc);
[R]D -4.3 (c 0.3, CHCl3); 1H NMR (500 MHz, CDCl3, δH)
7.40-7.22 (m, 15 H, Ar), 5.06 (d, 1 H, J1E,2E = 3.6 Hz, H-1E),
4.86 (s, 1 H, H-1C), 4.74-4.69 (m, 2 H, PhCH2O), 4.64-4.55 (m,
3 H, PhCH2O), 4.52 (d, 1 H, J=11.7 Hz, PhCH2O), 4.29-4.27
(m, 2 H, H-2C, H-5Ca), 4.26-4.19 (m, 2 H, H-5Ea, H-4C),
4.16-4.07 (m, 5 H, H-5Eb, H-5Cb, H-3E, H-2E, H-4E), 3.94
(dd, 1 H, J2C,3C =2.4 Hz, J3C,4C =6.0 Hz, H-3C), 3.37 (s, 3 H,
OCH3), 2.32-2.27 (m, 2 H, acyl CH2), 2.24-2.20 (m, 2 H, acyl
CH2), 1.62-1.50 (m, 4 H, acyl CH2 ꢀ 2), 1.34-1.20 (m, 48 H,
acyl CH2ꢀ24), 0.92-0.86 (m, 6 H, acyl CH3ꢀ2); 13C NMR (125
MHz, CDCl3, δC) 173.5 (CdO), 173.3 (CdO), 137.8 (Ar), 137.7
(Ar), 137.5 (Ar), 128.5(3) (Ar ꢀ 2), 128.4(5) (Ar ꢀ 2), 128.3(8)
(Arꢀ2), 128.1 (Ar), 128.0 (Arꢀ2), 127.8(5) (Ar), 127.7(9) (Ar),
J
2D,3D = 6.6 Hz, J3D,4D = 2.9 Hz, H-3D), 3.86-3.78 (m, 3 H,
H-3C, H-5Bb, H-5Db), 3.76 (dd, 1 H, J4C,5Ca=2.6 Hz, J5Ca,5Cb
12.2 Hz, H-5Ca), 3.66 (dd, 1 H, J4D,5 Da = 5.2 Hz, J5 Da,5Db
=
=
12.1 Hz, H-5 Da), 3.60 (dd, 1 H, J4C,5Cb=5.9 Hz, J5Ca,5Cb=12.2
Hz, H-5Cb), 3.40 (s, 3 H, OCH3); 13C NMR (125 MHz, CDCl3,
δC) 133.8 (Ar), 137.7 (Ar), 137.4(7) (Ar), 137.4(6) (Ar), 137.3
(Ar), 128.4(7) (Ar ꢀ 2), 128.4(5) (Ar ꢀ 3), 128.4(4) (Ar ꢀ 3),
128.4(2) (Arꢀ2), 128.4(0) (Arꢀ2), 127.9(6) (Ar), 127.9(5) (Arꢀ
2), 127.9(3) (Ar ꢀ 2), 127.8(8) (Ar), 127.8(5) (Ar ꢀ 3), 127.7(5)
(Ar), 127.7(3) (Ar ꢀ 3), 106.9 (C-1B), 106.2 (C-1C), 105.9
(C-1D), 88.8 (C-2B), 88.2 (C-2C), 87.6 (C-2D), 83.0(3) (C-3D),
83.0(0) (C-3C), 82.4 (C-4D), 82.0 (C-4C), 81.0 (C-3B), 79.8
(C-4B), 72.3 (PhCH2O), 72.2 (PhCH2O), 72.0 (PhCH2O), 71.9(7)
J. Org. Chem. Vol. 75, No. 15, 2010 5005

Liu et al.
JOCArticle
127.7(7) (Arꢀ2), 127.6(9) (Arꢀ2), 107.0 (C-1C), 100.7 (C-1E),
86.1 (C-2C), 84.1 (C-3C), 83.8 (C-2E), 82.5 (C-4E), 80.0 (C-4C),
78.9 (C-3E), 72.7 (PhCH2O), 72.5 (PhCH2O), 72.4 (PhCH2O),
65.9 (C-5E), 63.8 (C-5C), 54.9 (OCH3), 34.0(6) (acyl CH2),
34.0(5) (acyl CH2), 31.9 (acyl CH2), 29.7(0) (acyl CH2), 29.6(6)
(acyl CH2), 29.6(3) (acyl CH2), 29.5(1) (acyl CH2), 29.4(7) (acyl
CH2), 29.3(6) (acyl CH2), 29.3(2) (acyl CH2), 29.2(7) (acyl CH2),
29.1(7) (acyl CH2), 29.1(5) (acyl CH2), 24.8(7) (acyl CH2),
24.8(4) (acyl CH2), 22.7 (acyl CH2), 14.1 (acyl CH3ꢀ2); ESIMS
m/z calcd for [C64H98O11Na]þ 1065.7001, found 1065.7001.
Methyl 5-O-behenoyl-2,3-di-O-benzyl-β-D-arabinofuranosyl-
(1f2)-5-O-behenoyl-3-O-benzyl-r-D-arabinofuranoside (38):
Isolated as a colorless oil, 95%; Rf 0.68 (4:1 hexane-EtOAc);
[R]D þ0.4 (c 0.2, CHCl3); 1H NMR (500 MHz, CDCl3, δH)
7.40-7.22 (m, 15 H, Ar), 5.06 (d, 1 H, J1E,2E = 3.6 Hz, H-1E),
4.86 (s, 1 H, H-1C), 4.75-4.68 (m, 2 H, PhCH2O), 4.65-4.50 (m,
4 H, PhCH2O), 4.28 (dd, 1 H, J1C,2C =1.1 Hz, J2C,3C =2.7 Hz,
H-2C), 4.27-4.20 (m, 3 H, H-5Ca, H-5Ea, H-4C), 4.17-4.07
(m, 5 H, H-5Cb, H-5Eb, H-3E, H-2E, H-4E), 3.94 (dd, 1 H,
J2C,3C = 2.7 Hz, J3C,4C = 6.0 Hz, H-3C), 3.37 (s, 3 H, OCH3),
2.23-2.26 (m, 2 H, CH2), 2.25-2.21 (m, 2 H, CH2), 1.66-1.50
(m, 4 H, CH2ꢀ2), 1.38-1.10 (m, 72 H, CH2ꢀ36), 0.94-0.82 (m,
6 H, CH3 ꢀ2); 13C NMR (125 MHz, CDCl3, δC) 173.4 (CdO),
173.2 (CdO), 137.7 (Ar), 137.6 (Ar), 137.3 (Ar), 128.4(3) (Ar ꢀ
2), 128.3(4) (Arꢀ2), 128.2(8) (Arꢀ2), 127.9(5) (Ar), 127.9(2) (Arꢀ
2), 127.7(5) (Ar), 127.6(9) (Ar), 127.6(6) (Arꢀ2), 127.5(8) (Arꢀ
2), 106.9 (C-1C), 100.5 (C-1E), 86.0 (C-2C), 84.0 (C-4E), 83.7
(C-3C), 82.4 (C-2E), 79.8 (C-4C), 78.8 (C-3E), 72.6 (PhCH2O),
72.4 (PhCH2O), 72.3 (PhCH2O), 65.8 (C-5E), 63.7 (C-5C), 54.8
(OCH3), 34.0 (acyl CH2), 31.8 (acyl CH2), 29.6(1) (acyl CH2),
29.5(6) (acyl CH2), 29.5(3) (acyl CH2), 29.4(2) (acyl CH2), 29.3(8)
(acyl CH2), 29.2(6) (acyl CH2), 29.2(3) (acyl CH2), 29.1(8) (acyl
CH2), 29.0(7) (acyl CH2), 29.0(5) (acyl CH2), 24.7(7) (acyl CH2),
24.7(3) (acyl CH2), 22.6 (acyl CH2), 14.0 (acyl CH3ꢀ2); ESIMS
m/z calcd for [C76H122O11Na]þ 1233.8879, found 1233.8878.
Methyl 2,3-di-O-benzyl-5-O-butyryl-r-D-arabinofuranosyl-(1f3)-
[2,3-di-O-benzyl-5-O-butyryl-r-D-arabinofuranosyl-(1f5)]-2-O-
benzyl-r-D-arabinofuranoside (39): Isolated as a colorless oil,
95%; Rf 0.25 (4:1 hexane-EtOAc); [R]D þ76.2 (c 0.2, CHCl3);
1H NMR (500 MHz, CDCl3, δH) 7.37-7.22 (m, 25 H, Ar), 5.19
(s, 1 H, H-1C), 5.15 (s, 1 H, H-1D), 4.93 (s, 1 H, H-1B),
4.60-4.43 (m, 9 H, PhCH2O), 4.38 (d, 1 H, J = 11.7 Hz, Ph-
CH2O), 4.30-4.24 (m, 4 H, H-3B, H-5Ca, H-5 Da, H-4C),
oil, 89%; Rf 0.50 (4:1 hexane-EtOAc); [R]D þ35.4 (c 0.2,
1
CHCl3); H NMR (600 MHz, CDCl3, δH) 7.37-7.23 (m, 25 H,
Ar), 5.19 (d, 1 H, J1C,2C=1.2 Hz, H-1C), 5.15 (d, 1 H, J1D,2D =
1.2 Hz, H-1D), 4.93 (d, 1 H, J1B,2B =1.2 Hz, H-1B), 4.60-4.44
(m, 9 H, PhCH2O), 4.38 (d, 1 H, J = 11.8 Hz, PhCH2O),
4.30-4.24 (m, 4 H, H-3B, H-5Ca, H-5 Da, H-4C), 4.22-4.17
(m, 3 H, H-5Cb, H-5Db, H-4D), 4.13 (ddd, 1 H, J3B,4B=7.0 Hz,
J4B,5Ba=4.6 Hz, J4B,5Bb=2.5 Hz, H-4B), 4.10 (dd, 1 H, J1C,2C
1.2 Hz, J2C,3C =3.4 Hz, H-2C), 4.06 (dd, 1 H, J1D,2D =1.2 Hz,
2D,3D=3.4 Hz, H-2D), 3.99 (dd, 1 H, J1B,2B=1.2 Hz, J2B,3B
=
J
=
3.3 Hz, H-2B), 3.95 (dd, 1 H, J4B,5Ba = 4.6 Hz, J5Ba,5Bb = 11.9
Hz, H-5Ba), 3.88-3.85 (m, 2 H, H-3C, H-3D), 3.78 (dd, 1 H,
J4B,5Bb = 2.5 Hz, J5Ba,5Bb = 11.9 Hz, H-5Bb), 3.38 (s, 3 H,
OCH3), 2.30-2.25 (m, 4 H, acyl CH2 ꢀ 2), 1.60-1.54 (m, 4 H,
acyl CH2 ꢀ 2), 1.34-1.22 (m, 24 H, acyl CH2 ꢀ 12), 0.92-0.87
(m, 6 H, acyl CH3 ꢀ2); 13C NMR (125 MHz, CDCl3, δC) 173.6
(CdO), 173.5 (CdO), 137.7 (Ar), 137.6(3) (Ar), 137.5(7) (Ar),
137.4 (Ar), 137.3 (Ar), 128.5 (Arꢀ2), 128.4(2) (Arꢀ3), 128.4(0)
(Ar ꢀ 3), 128.3(5) (Ar ꢀ 2), 127.9(6) (Ar), 127.9(2) (Ar ꢀ 2),
127.8(9) (Arꢀ2), 127.8(5) (Arꢀ3), 127.7(9) (Arꢀ2), 127.7(6) (Arꢀ
2), 127.7(3) (Ar ꢀ2), 127.7(1) (Ar), 107.1 (C-1B), 106.5 (C-1C),
105.5 (C-1D), 88.3 (C-2B), 88.1 (C-2C), 88.0 (C-2D), 83.4(3)
(C-3C), 83.3(5) (C-3D), 80.8 (C-4B), 80.5 (C-3B), 79.2 (C-4D),
79.0 (C-4C), 72.2 (PhCH2O), 72.1 (PhCH2O), 72.0 (PhCH2O ꢀ
2), 71.8 (PhCH2O), 65.8 (C-5B), 63.3 (C-5D), 63.2 (C-5C), 54.8
(OCH3), 34.1 (acyl CH2), 34.0 (acyl CH2), 31.9 (acyl CH2), 29.4
(acyl CH2), 29.3(0) (acyl CH2), 29.2(8) (acyl CH2), 29.1(6) (acyl
CH2), 24.8 (acylCH2), 22.7 (acylCH2), 14.1 (acylCH3ꢀ2); ESIMS
m/z calcd for [C71H94O15Na]þ 1209.6485, found 1209.6489.
Methyl 2,3-di-O-benzyl-5-O-palmitoyl-r-D-arabinofuranosyl-
(1f3)-[2,3-di-O-benzyl-5-O-palmitoyl-r-D-arabinofuranosyl-(1f5)]-
2-O-benzyl-r-D-arabinofuranoside (41): Isolated as a colorless
oil, 89%; Rf 0.45 (4:1 hexane-EtOAc); [R]D þ40.8 (c 0.2,
1
CHCl3); H NMR (500 MHz, CDCl3, δH) 7.37-7.22 (m, 25
H, Ar), 5.19 (d, 1 H, J1C,2C=1.1 Hz, H-1C), 5.15 (d, 1 H, J1D,2D
=
1.1 Hz, H-1D), 4.93 (d, 1 H, J1B,2B =1.2 Hz, H-1B), 4.60-4.43
(m, 9 H, PhCH2O), 4.38 (d, 1 H, J = 11.8 Hz, PhCH2O),
4.30-4.23 (m, 4 H, H-3B, H-5Ca, H-5 Da, H-4C), 4.22-4.16
(m, 3 H, H-5Cb, H-5Db, H-4D), 4.13 (ddd, 1 H, J3B,4B=7.0 Hz,
J
4B,5Ba=4.6 Hz, J4B,5Bb=2.5 Hz, H-4B), 4.10 (dd, 1 H, J1C,2C
1.2 Hz, J2C,3C =3.4 Hz, H-2C), 4.03 (dd, 1 H, J1D,2D =1.1 Hz,
J2D,3D=3.4 Hz, H-2D), 3.98 (dd, 1 H, J1B,2B=1.2 Hz, J2B,3B
=
=
3.3 Hz, H-2B), 3.95 (dd, 1 H, J4B,5Ba = 4.6 Hz, J5Ba,5Bb = 11.9
Hz, H-5Ba), 3.88-3.84 (m, 2 H, H-3C, H-3D), 3.78 (dd, 1 H,
J4B,5Bb = 2.5 Hz, J5Ba,5Bb = 11.9 Hz, H-5Bb), 3.38 (s, 3 H,
OCH3), 2.29-2.24 (m, 4 H, acyl CH2 ꢀ 2), 1.60-1.53 (m, 4 H,
acyl CH2 ꢀ 2), 1.34-1.20 (m, 48 H, acyl CH2 ꢀ 24), 0.92-0.87
(m, 6 H, acyl CH3 ꢀ2); 13C NMR (125 MHz, CDCl3, δC) 173.6
(CdO), 173.5 (CdO), 137.8 (Ar), 137.6(4) (Ar), 137.5(8) (Ar),
137.4 (Ar), 137.3 (Ar), 128.5 (Arꢀ2), 128.4(1) (Arꢀ2), 128.3(8)
(Ar ꢀ 4), 128.3(4) (Ar ꢀ 2), 127.9(4) (Ar), 127.9(0) (Ar ꢀ 2),
127.8(8) (Arꢀ2), 127.8(4) (Arꢀ4), 127.7(7) (Ar), 127.7(4) (Arꢀ
2), 127.7(2) (Ar ꢀ2), 127.6(9) (Ar), 107.1 (C-1B), 106.5 (C-1C),
105.5 (C-1D), 88.3 (C-2B), 88.1(4) (C-2C), 88.0(7) (C-2D), 83.5
(C-3C), 83.4 (C-3D), 80.8 (C-4B), 80.5 (C-3B), 79.2 (C-4D), 79.0
(C-4C), 72.2 (PhCH2O), 72.1 (PhCH2O), 72.0 (PhCH2O), 71.9
(PhCH2O), 71.8 (PhCH2O), 65.8 (C-5B), 63.3 (C-5D), 63.2
(C-5C), 54.8 (OCH3), 34.1 (acyl CH2), 34.0 (acyl CH2), 31.9
(acyl CH2), 29.7(1) (acyl CH2), 29.6(9) (acyl CH2), 29.6(6) (acyl
CH2), 29.5 (acyl CH2), 29.4 (acyl CH2), 29.3(2) (acyl CH2),
29.3(0) (acyl acyl CH2), 29.2 (acyl CH2), 24.8 (acyl CH2), 22.7
4.22-4.16 (m, 3 H, H-5Cb, H-5Db, H-4D), 4.13 (ddd, 1 H, J3B,4B
7.0 Hz, J4B,5Ba=4.7 Hz, J4B,5Bb=2.5 Hz, H-4B), 4.10 (dd, 1 H,
1C,2C=1.3 Hz, J2C,3C=3.4 Hz, H-2C), 4.06 (dd, 1 H, J1D,2D
1.3 Hz, J2D,3D =3.4 Hz, H-2D), 3.97 (dd, 1 H, J1B,2B =1.3 Hz,
2B,3B=3.2 Hz, H-2B), 3.95 (dd, 1 H, J4B,5Ba=4.7 Hz, J5Ba,5Bb
=
J
=
J
=
11.9 Hz, H-5Ba), 3.88-3.83 (m, 2 H, H-3C, H-3D), 3.78 (dd,
1 H, J4B,5Bb =2.5 Hz, J5Ba,5Bb =11.9 Hz, H-5Bb), 3.38 (s, 3 H,
OCH3), 2.28-2.22 (m, 4 H, acyl CH2 ꢀ 2), 1.70-1.56 (m, 4 H,
acyl CH2ꢀ2), 0.92-0.87 (m, 6 H, acyl CH3ꢀ2); 13C NMR (125
MHz, CDCl3, δC) 173.4 (CdO), 173.3 (CdO), 137.7 (Ar), 137.6
(Ar), 137.5 (Ar), 137.4 (Ar), 137.3 (Ar), 128.5 (Arꢀ2), 128.4(3)
(Ar ꢀ 2), 128.4(0) (Ar ꢀ 2), 128.3(9) (Ar ꢀ 2), 128.3(6) (Ar ꢀ 2),
127.9(6) (Ar), 127.9(3) (Arꢀ2), 127.9(1) (Arꢀ2), 127.8(5) (Arꢀ
4), 127.8(0) (Ar), 127.7(8) (Ar ꢀ 2), 127.7(5) (Ar ꢀ 2), 127.7(2)
(Ar), 107.1 (C-1B), 106.5 (C-1C), 105.5 (C-1D), 88.3 (C-2B),
88.1(4) (C-2C), 88.0(5) (C-2D), 83.4(4) (C-3C), 83.3(6) (C-3D),
80.8 (C-4B), 80.5 (C-4C), 79.2 (C-4D), 78.9 (C-3B), 72.2 (Ph-
CH2O), 72.1 (PhCH2O), 72.0(2) (PhCH2O), 72.0(0) (PhCH2O),
71.8 (PhCH2O), 65.8 (C-5B), 63.3(4) (C-5C), 63.3(0) (C-5D),
54.8 (OCH3), 35.9(3) (acyl CH2), 35.9(1) (acyl CH2), 18.3(2)
(acyl CH2), 18.3(1) (acyl CH2), 13.6 (acyl CH3 ꢀ2); ESIMS m/z
calcd for [C59H70O15Na]þ 1041.4607, found 1041.4604.
(acyl CH2), 14.1 (acyl CH3 ꢀ2); ESIMS m/z calcd for [C83H118
-
O15Na]þ 1377.8363, found 1377.8369.
Methyl 5-O-behenoyl-2,3-di-O-benzyl-r-D-arabinofuranosyl-
(1f3)-[5-O-behenoyl-2,3-di-O-benzyl-r-D-arabinofuranosyl-(1f5)]-
2-O-benzyl-r-D-arabinofuranoside (42): Isolated as a colorless
oil, 81%; Rf 0.64 (4:1 hexane-EtOAc); [R]D þ51.2 (c 1.3, CHCl3);
1H NMR (600 MHz, CDCl3, δH) 7.36-7.23 (m, 25 H, Ar), 5.18
Methyl 2,3-di-O-benzyl-5-O-decanoyl-r-D-arabinofuranosyl-
(1f3)-[2,3-di-O-benzyl-5-O-decanoyl-r-D-arabinofuranosyl-(1f5)]-
2-O-benzyl-r-D-arabinofuranoside (40): Isolated as a colorless
5006 J. Org. Chem. Vol. 75, No. 15, 2010

Liu et al.
JOCArticle
(d, 1 H, J1C,2C = 0.8 Hz, H-1C), 5.14 (d, 1 H, J1D,2D = 0.9 Hz,
H-1D), 4.92 (d, 1 H, J1B,2B=0.9 Hz, H-1B), 4.59-4.42 (m, 9 H,
PhCH2O), 4.37 (d, 1 H, J = 11.8 Hz, PhCH2O), 4.29-4.22 (m,
4 H, H-3B, H-5Ca, H-5 Da, H-4C), 4.21-4.16 (m, 3 H, H-5Cb,
H-5Db, H-4D), 4.12 (ddd, 1 H, J3B,4B=7.0 Hz, J4B,5Ba=4.7 Hz,
71.8 (PhCH2O), 65.8 (C-5B), 63.3 (C-5D), 63.2 (C-5C), 54.8
(OCH3), 34.1 (acyl CH2), 34.0 (acyl CH2), 31.9 (acyl CH2),
29.7(2) (acyl CH2), 29.6(7) (acyl CH2), 29.5 (acyl CH2), 29.4
(acyl CH2), 29.3(4) (acyl CH2), 29.3(2) (acyl CH2), 29.2 (acyl
CH2), 24.8 (acyl CH2), 22.7 (acyl CH2), 14.1 (acyl CH3 ꢀ 2);
ESIMS m/z calcd for [C95H142O15Na]þ 1546.0241, found
1546.0244.
J4B,5Bb=2.6 Hz, H-4B), 4.09 (dd, 1 H, J1C,2C=1.1 Hz, J2C,3C=
3.4 Hz, H-2C), 4.02 (dd, 1 H, J1D,2D =1.1 Hz, J2D,3D =3.4 Hz,
H-2D), 3.97 (dd, 1 H, J1B,2B = 1.1 Hz, J2B,3B = 3.3 Hz, H-2B),
3.94 (dd, 1 H, J4B,5Ba = 4.7 Hz, J5Ba,5Bb = 11.8 Hz, H-5Ba),
3.87-3.83 (m, 2 H, H-3C, H-3D), 3.77 (dd, 1 H, J4B,5Bb = 2.6
Hz, J5Ba,5Bb=11.8 Hz, H-5Bb), 3.37 (s, 3 H, OCH3), 2.30-2.22
(m, 4 H, acyl CH2 ꢀ 2), 1.60-1.50 (m, 4 H, acyl CH2 ꢀ 2),
1.36-1.20 (m, 72 H, acyl CH2ꢀ36), 0.92-0.84 (m, 6 H, acyl CH3ꢀ
2); 13C NMR (125 MHz, CDCl3, δC) 173.6 (CdO), 173.5
(CdO), 137.8 (Ar), 137.6(4) (Ar), 137.5(7) (Ar), 137.4 (Ar),
137.3 (Ar), 128.5 (Ar ꢀ 2), 128.4(3) (Ar ꢀ 2), 128.3(9) (Ar ꢀ 3),
128.3(5) (Arꢀ2), 127.9(6) (Ar), 127.9(2) (Arꢀ3), 127.8(9) (Arꢀ
3), 127.8(6) (Ar ꢀ 3), 127.7(9) (Ar), 127.7(6) (Ar ꢀ 2), 127.7(3)
(Arꢀ2), 127.7(1) (Ar), 107.1 (C-1B), 106.5 (C-1C), 105.5 (C-1D),
88.3 (C-2B), 88.1(3) (C-2C), 88.0(5) (C-2D), 83.4(3) (C-3C),
83.3(6) (C-3D), 80.8 (C-4B), 80.5 (C-3B), 79.2 (C-4D), 79.0
(C-4C), 72.2 (PhCH2O), 72.1 (PhCH2O), 72.0 (PhCH2O ꢀ 2),
Acknowledgment. This work was supported by the Alberta
Ingenuity Centre for Carbohydrate Science and the Natural
Sciences and Engineering Research Council of Canada. M.R.R.
is supported by an Alberta Heritage Foundation for Medical
Research Ph.D. studentship.
Supporting Information Available: Examples of simulated
1H NMR spectra used to determine the coupling constants in
Tables 3 and 4; computational methods and Cartesian coordi-
nates for methyl 5-O-acetyl-R-D-arabinofuranoside used to deter-
mine eqs 6 and 7; 1H and 13C NMR spectra of new compounds.
This material is available free of charge via the Internet at http://
pubs.acs.org.
J. Org. Chem. Vol. 75, No. 15, 2010 5007