Conversion of pyranose glycals to furanose derivatives: A new route to oligofuranosides

Article abstract of DOI:10.1021/jo9815406

Acetylated pyranose glycals have been converted through a convenient three-step process into protected furanose reducing sugars. Ozonolysis of 2,3,5-tri-O-acetyl-glucal or 2,3,5-tri-O-acetylgalactal, followed by treatment with dimethyl sulfide and then hydrolysis gave respectively protected arabinofuranose (6) and lyxofuranose (7) derivatives. Conversion of these hemiacetals to oligosaccharides was explored using a number of methods. Activation of 6 or 7 in situ afforded glycosides in modest yield and stereoselectivity. Glycosylation of tetraacetates 16 and 18, obtained from 6 and 7, gave similar results. However, thioglycosides 17 and 19, also derived from 6 and 7, were found to be effective glycosyl donors, producing products in good to excellent yields and with high stereoselectivities. The method was also used to synthesize a disaccharide in which one residue contained uniform ¹³C enrichment.

Full text of DOI:10.1021/jo9815406

J . Org. Chem. 1998, 63, 9037-9044
9037
Con ver sion of P yr a n ose Glyca ls to F u r a n ose Der iva tives: A New
Rou te to Oligofu r a n osid es
Francis W. D’Souza, Pavel E. Cheshev, J oseph D. Ayers, and Todd L. Lowary*
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210
Received J uly 31, 1998
Acetylated pyranose glycals have been converted through a convenient three-step process into
protected furanose reducing sugars. Ozonolysis of 2,3,5-tri-O-acetyl-glucal or 2,3,5-tri-O-acetyl-
galactal, followed by treatment with dimethyl sulfide and then hydrolysis gave respectively protected
arabinofuranose (6) and lyxofuranose (7) derivatives. Conversion of these hemiacetals to oligosac-
charides was explored using a number of methods. Activation of 6 or 7 in situ afforded glycosides
in modest yield and stereoselectivity. Glycosylation of tetraacetates 16 and 18, obtained from 6
and 7, gave similar results. However, thioglycosides 17 and 19, also derived from 6 and 7, were
found to be effective glycosyl donors, producing products in good to excellent yields and with high
stereoselectivities. The method was also used to synthesize a disaccharide in which one residue
contained uniform 13C enrichment.
In tr od u ction
sylation reaction (Scheme 1).7 The furanosides are the
kinetic products, and at short reaction times modest to
good yields of these isomers are obtained. Methyl gly-
cosides are typically synthesized by this approach, and
conversion to a derivative (e.g., glycosyl halide, thiogly-
coside) suitable for oligosaccharide synthesis requires
further manipulation. Recently, both Fraser-Reid8 and
Plusquellec9 have reported that Fisher glycosylation of
hexoses with 4-penten-1-ol yields glycosides that can,
after protection of the hydroxyl groups, be used directly
in glycosylation reactions. A related approach is the
high-temperature acylation of unprotected sugars to
generate a fully acylated furanose that can be used as a
Oligosaccharides containing furanose moieties are
important constituents of a number of lower organisms
including bacteria,1 parasites,2 fungi,3 and plants.4 The
most spectacular examples of these glycans are found in
mycobacteria, including Mycobacterium tuberculosis. An
integral constituent of the protective cell wall of this
organism is an arabinogalactan in which all of the
arabinose and galactose residues exist in the furanose
form.1 Because furanose oligosaccharides are unknown
in humans and, at the same time, are critical for the
survival of mycobacteria and other pathogenic organisms,
the enzymes that assemble them are ideal targets for
drug action. Consequently, there has been increasing
interest in the synthesis of furanose oligosaccharides and
related analogues that could act as either glycosyltrans-
ferase substrates5 or inhibitors.6 However, in comparison
with their pyranosidic counterparts, there has been
relatively little work directed toward synthesizing oligo-
furanosides.
glycosyl donor upon activation with a Lewis acid.10
A
disadvantage of these approaches is that yields are
variable from sugar to sugar, and the reaction mixtures
are sometimes contaminated with pyranose isomers
which complicate purification. An alternative method
Sch em e 1a
The majority of free hexoses and pentoses exist pre-
dominately in the pyranose form, and the preparation of
furanosides is most often achieved by subjecting an
unprotected reducing sugar to a controlled Fisher glyco-
(1) Brennan, P. J .; Nikaido, H. Annu. Rev. Biochem. 1995, 64, 29.
(2) (a) Gerold, P.; Eckert, V.; Schwarz, R. T. Trends Glycosci.
Glycotechnol. 1996, 8, 265. (b) de Lederkremer, R. M.; Colli, W.
Glycobiology 1995, 5, 547.
(3) (a) Unkefer, C. J .; Gander, J . J . Biol. Chem. 1990, 265, 685. (b)
Mendonc¸a-Previato, L.; Gorin, P. A. J . Infect. Immun. 1980, 29, 934.
(c) Groisman, J . F.; de Lederkremer, R. M. Eur. J . Biochem. 1987, 165,
327.
(4) Kils, F. M. New Compr. Biochem. 1995, 29a, 511.
(5) (a) Ayers, J . D.; Lowary, T. L.; Morehouse, C. B.; Besra, G. S.
Bioorg. Med. Chem. Lett. 1998, 8, 437. (b) Lee, R. E.; Brennan, P. J .;
Besra, G. S. Glycobiology 1997, 7, 1121. (c) Gallo-Rodriquez, C.; Varela,
O.; de Lederkremer, R. M. J . Org. Chem. 1996, 61, 1886. (d) Mereyala,
H. B.; Hotha, S.; Gurjar, M. K. J . Chem. Soc., Chem. Commun. 1998,
685.
(6) (a) Bouix, C. B.; Bisseret, P.; Eustache, J . Tetrahedron Lett. 1998,
39, 825. (b) Maddry, J . A.; Bansal, N.; Bermudez, L. E.; Comber, R.
N.; Orme, I. M.; Suling, W. J .; Wilson, L. N.; Reynolds, R. C.
Tetrahedron Lett. 1998, 39, 237. (c) Lee, R. E.; Smith, M. D.; Nash, R.
J .; Griffiths, R. C.; McNeil, M.; Grewal, R. K.; Yan, W.; Besra, G. S.;
Brennan, P. J .; Fleet, G. W. J . Tetrahedron Lett. 1997, 38, 6733.
a
P ) protecting group; X ) activatable group.
(7) Green, J . W. Adv. Carbohydr. Chem. Biochem. 1966, 21, 95.
(8) Arasappan, A.; Fraser-Reid, B. Tetrahedron Lett. 1995, 38, 7667.
(9) Velty, R.; Benvegnu, T.; Gelin, M.; Privat, E.; Plusquellec, D.
Carbohydr. Res. 1997, 299, 7 and references therein.
(10) Varela, O.; Marino, M. C.; de Lederkremer, R. M. Carbohydr.
Res. 1986, 155, 247.
10.1021/jo9815406 CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/06/1998

9038 J . Org. Chem., Vol. 63, No. 24, 1998
D’Souza et al.
Sch em e 2
Sch em e 4a
a
(a) O3, NaHCO3, CH2Cl2, CH3OH, -78 °C. (b) (CH3)2S, -78
(Scheme 2) involves the conversion of sugar dithioacetals
to mixed S,O acetals and then cyclization to furanosidic
glycosides. This method was developed over 50 years ago
by Wolfrom for the synthesis of furanosides of simple
alcohols;7,11 more recently it has been applied to the pre-
paration of oligosaccharides.12 This route provides fura-
nosides in the absence of pyranosides; however, a number
of steps are required to carry out this transformation.
As part of a program directed at the synthesis of
furanose oligosaccharides, we were interested in develop-
ing alternate routes to furanose monosaccharides that
could be converted to suitable glycosylating agents. We
demonstrate here that acetylated pyranose glycals can
be converted efficiently to furanose glycosyl donors and,
in turn, oligosaccharides.
°C f rt. (c) HOAc, CH3OH (3:2), 70 °C.
and (2) the product formed is already protected and can
be activated either directly or indirectly and used as a
glycosyl donor. Furthermore, in contrast to the dithio-
acetal cyclization route to furanosides, we envisioned that
it would be possible to carry out the conversion of 1 into
3 without purification of the intermediate, hence adding
to the overall efficiency of the process.
Syn th esis of P r otected F u r a n ose Red u cin g Su g-
a r s. Relatively few reports describe the ozonolysis of
glycals. Reiser and co-workers16 have reported that
ozonolysis of tri-O-acetyl-D-glucal (4) followed by treat-
ment with acetic anhydride and triethylamine affords a
4-formyloxy-D-arabinonic acid methyl ester derivative.
Similarly, tri-O-benzyl-D-glucal has been converted to
2,3,5-tri-O-benzyl-4-formyloxy-D-arabinose (2, P ) Bn)
upon treatment with ozone followed by dimethyl sulfide.17
As illustrated in Scheme 4, ozonolysis of 4 in a mixture
of methanol and dichloromethane in the presence of
sodium bicarbonate16 was followed by treatment with
dimethyl sulfide to give a formyl aldehyde (Scheme 3, 2,
P ) Ac). This product was not purified but rather the
reaction mixture was evaporated, dissolved in methanol,
filtered, and re-evaporated to give a residue that was
heated overnight in acetic acid/methanol (3:2) at 70 °C.
Under these conditions, the formate ester was selectively
cleaved, thus producing 2,3,5-tri-O-acetyl-D-arabinofura-
nose (6) in 72% yield from 4 after chromatography. A
similar sequence of reactions was carried out on tri-O-
acetyl-D-galactal (5) to give the D-lyxofuranose analogue
7 in 62% overall yield.
Resu lts a n d Discu ssion
Pyranose glycals are readily accessible synthetic in-
termediates, and many are commercially available. These
versatile compounds have been used widely in organic
synthesis for the preparation of oligosaccharides,13 C-
glycosides,14 and other natural products.15 It occurred
to us (Scheme 3) that ozonolysis of a protected pyranose
Sch em e 3a
The conversion of 4 into 6 through the use of an in situ
dihydroxylation/oxidative cleavage protocol was also
investigated. However, treatment of 4 with osmium
tetroxide and sodium periodate, as reported for 3,4-di-
O-acetyl-D-xylal,18 gave low product yields and significant
amounts of unreacted starting material. A number of
reaction conditions were also explored for the cleavage
of the formate ester including silica gel in methanol,19
refluxing methanol,20 and morpholine,16 but all gave
results inferior to the described mixture of acetic acid and
methanol.
Glycosyla tion Rea ction s. We had hoped that in situ
activation of the hydroxyl group would enable us to
construct glycosides directly from hemiacetals 6 and 7
(Scheme 5). While such methods are available,21 most
involve donors containing alkyl protecting groups and
thus are activated relative to 6 and 7. Nevertheless, we
a
P ) protecting group.
glycal (1) followed by a reductive workup and selective
cleavage of the resulting formate ester (2) would produce
a hydroxy-aldehyde that would spontaneously cyclize to
give a protected furanose derivative (3). This route offers
advantages over the Fisher glycosylation process in that
(1) pyranoside formation is not a possible side reaction
(11) Wolfrom, M. L.; Weisblat, D. I.; Hanze, A. R. J . Am. Chem. Soc.
1944, 66, 2065.
(12) McAuliffe, J . C.; Hindsgaul, O. J . Org. Chem. 1997, 62, 1234.
(13) (a) Danishefsky, S. J .; Bilodeau, M. T. Angew. Chem., Int. Ed.
Engl. 1996, 35, 1380. (b) Kwon, O.; Danishefsky, S. J . J . Am. Chem.
Soc. 1998, 120, 1588 and references therein.
(14) Postema, M. H. D. C-Glycoside Synthesis; CRC Press: Boca
Raton, 1995.
(15) (a) Ireland, R. E.; Thaisrivongs, S.; Varier, N.; Wilcox, C. S. J .
Org. Chem. 1980, 45, 48. (b) Corey, E. J .; Goto, G. Tetrahedron Lett.
1980, 21, 3463. (c) Yenjai, C.; Isobe, M. Tetrahedron 1998, 54, 2509.
(16) Hillers, S.; Niklaus, A.; Reiser, O. J . Org. Chem. 1993, 58, 3169.
(17) Kaluza, Z.; Manhas, M. S.; Barakat, K. J .; Ajay, A. K. Bioorg.
Med. Chem. Lett. 1993, 3, 2357.
(18) Harvey, T. C.; Simiand, C.; Weiler, L.; Withers, S. G. J . Org.
Chem. 1997, 62, 6722.
(19) Avalos, M.; Babiano, R.; Cintas, P.; J ime´nez, J . L.; Palacios, J .
C.; Valencia, C. Tetrahedron. Lett. 1993, 34, 1359.
(20) Zemlicka, J .; Bera´nek, J .; Smrt, J . Collect. Czech. Chem.
Commun. 1962, 27, 2784.

Pyranose Glycals to Furanose Derivatives
J . Org. Chem., Vol. 63, No. 24, 1998 9039
Sch em e 5a
Sch em e 6
a
(a) Yb(OTf)3, CH3OCH2CO2H. (b) Tf2O, Ph2SO, 2-chloropyri-
dine.
Ta ble 1. Glycosyla tion of 6, 7, a n d 16-19
entry donor ROHa conditnsb yield (%)c R:â ratiod product
1
2
6
6
8
9
10
8
9
Ae
A
A
B
49
37
21
45
50
19
NRg
10
21
62
65
54
82
86
79
71
85
69
76
65
10:1
10:3
2:1
R
20:3
4:1
20
22
23
20
22
23
24
24
23
24
20
22
23
25
28
21
24
26
27
29
3
6
4
6
Given that 6 contains an acetyl protecting group on
O-2, it was expected that only the 1,2-trans-glycosides
would be formed through intermediate 14 because of
neighboring group participation (Scheme 7). We were
therefore initially surprised when significant amounts of
the 1,2-cis-glycosides were formed. However, the forma-
tion of â-glycosides as byproducts in the glycosylation of
acylated arabinofuranose derivatives has been previously
described.23 For example, Lewis acid promoted glycosy-
lation of a number of alcohols by tetraacetate 16 has been
reported to give almost equal amounts of both glycoside
anomers in low yields.23b A plausible explanation (Scheme
7) for the erosion of stereocontrol is that there is
participation underneath the ring by the acyl group on
O-3 giving intermediate 15, which in turn would lead to
the â-arabinofuranoside. Such participation has previ-
ously been invoked and used to advantage in the syn-
thesis of 2-deoxy â-D-nucleosides and C-glycosides.24
5
6
B
6
6
10
10
10
10
10
8
B
A
B
C
C
7
7
8
7
R
9
16
18
17
17
17
17
17
19
19
19
19
19
2:1
3:1
R
10
11
12
13
14
15
16
17
18
19
20
Df
D
D
D
D
Df
D
D
D
D
9
R
10
11
13
8
R
R
R
R
10
11
12
13
R
R
R
R
a
For 8 and 9, 3-5 equiv of alcohol was added relative to donor;
for 10-13,1.0-1.2equiv. b A.donor (1.0equiv),ROH,CH3OCH2CO2H
(1.0 equiv), Yb(OTf)3 (0.2 equiv), CH2Cl2, reflux. B. donor (1.0
equiv), ROH, Ph2SO (2.8 equiv), Tf2O (1.4 equiv), 2-chloropyridine
(5.0 equiv), -40 °C f rt. C. donor (1.0 equiv), ROH, SnCl4 (1.0
equiv), rt. D. donor (1.0 equiv), ROH, NIS (1.3 equiv), AgOTf (0.3
equiv), 0 °C. c Isolated yield after chromatography. Ratio deter-
d
Sch em e 7
mined by 1H NMR of chromatographed product. e Reaction carried
out at rt. f Reaction done in CH3CN. No reaction observed; see
g
text.
explored this possibility by first attempting the glycosy-
lation of 6 with alcohols 8-10 using a method reported
by Inanga and co-workers.21a Upon treatment of 6 with
these alcohols under the described conditions (methoxy
acetic acid in a refluxing solution of dichloromethane
containing catalytic ytterbium triflate), only modest
yields of the glycosides were obtained (Table 1, entries
1-3). Furthermore, significant quantities of the 1,2-cis-
glycosides were produced. Separation of these products
proved impossible because of their identical chromato-
graphic properties.
We next investigated a recently reported method
involving direct activation of the anomeric center by
diphenyl sulfoxide and triflic anhydride in the presence
of 2-chloropyridine22 (Scheme 5). This method has been
shown to give excellent yields for both alkylated and
acylated pyranose reducing sugars; when O-2 is acylated,
the 1,2-trans-glycosides are formed exclusively. How-
ever, again, glycosylation of alcohols 8-10 with 6 gave
modest product yields. Although the stereoselectivities
were better with some alcohols, with others, inseparable
mixtures were still produced (Table 1, entries 4-6).
To investigate this possibility, we then examined the
glycosylation of the lyxofuranose derivative 7. If par-
ticipation of the protecting group on O-3 is a major factor
in determining the stereochemical outcome of glycosyla-
tions with 6, then 7 should give higher stereoselectivities.
Unfortunately, reaction of 7 with 10 failed to give any
product in the case of one activating system and gave
only very low yields of product in the other (Table 1,
entries 7 and 8). In both cases, even at long reaction
times and with the addition of more promoter, significant
(21) (a) Inanga, J .; Yokoyama, Y.; Hanamoto, T. J . Chem. Soc.,
Chem. Commun. 1993, 1090. (b) Uchiro, H.; Mukaiyama, T. Chem. Lett.
1996, 79. (c) Uchiro, H.; Mukaiyama, T. Chem. Lett. 1996, 271. (d)
Suda, S.; Mukaiyama, T. Chem. Lett. 1991, 431. (e) Mukaiyama, T.;
Suda, S. Chem. Lett. 1990, 1143. (f) Koto, S.; Sato, T.; Morishima, N.;
Zen, S. Bull. Chem. Soc. J pn. 1980, 53, 1761. (g) Mukaiyama, T.;
Matsubara, K.; Hora, M. Synlett 1994, 1368.
(23) (a) Pathak, A. K.; El-Kattan, Y. A.; Bansal, N.; Maddry, J . A.;
Reynolds, R. C. Tetrahedron Lett. 1998, 39, 1497. (b) Mizutani, K.;
Kasai, R.; Nakamura, M.; Tanaka, O.; Matsuura, H. Carbohydr. Res.
1989, 185, 27.
(24) (a) Mukaiyama, T.; Hirano, N.; Nishida, M.; Uchiro, H. Chem.
Lett. 1996, 99. (b) Mukaiyama, T.; Uchiro, H.; Hirano, N.; Ishikawa,
T. Chem. Lett. 1996, 629.
(22) Garcia, B. A.; Poole, J . L.; Gin, D. Y. J . Am. Chem. Soc. 1997,
119, 7597.

9040 J . Org. Chem., Vol. 63, No. 24, 1998
D’Souza et al.
Sch em e 8a
Sch em e 9
a
(a) Ac2O, H2SO4, 0 °C, 99%. (b) CrSH, BF3OEt2, 0 °C, 85%. (c)
CrSH, BF3OEt2, 0 °C, 80%.
amounts of unreacted starting materials were recovered.
Although the use of the diphenyl sulfoxide/triflic anhy-
dride promoter system gave the product with excellent
stereocontrol, the low yields prompted us to explore other
glycosyl donors. We then synthesized tetraacetates 16
and 18 from 6 and 7, respectively (Scheme 8). Reaction
of both donors with alcohol 10 in the presence of tin(IV)
chloride gave mixtures of glycosides (Table 1, entries 9
and 10). In the case of the lyxo analogue 18, the
selectivity for the R product was slightly greater than
that in the arabino analogue 16. However, the formation
of substantial amounts of the â-glycoside from 18 sug-
gests that while participation under the ring by a
protecting group on O-3 may contribute to poor glycosy-
lation stereocontrol with some arabinose donors (e.g., 6
and 16), it is not the only factor.
We then turned our attention to activation of these
sugars indirectly by way of thioglycosides 17 and 19. The
former has previously been shown to efficiently glycosy-
late both primary and secondary carbohydrate alcohols.5a
The required thiocresyl donors were synthesized from 16
and 18 without incident in 80-85% yield (Scheme 8).
Glycosylation of alcohols 8-13 with either 17 or 19 gave
the desired products in good to excellent yields with high
stereoselectivities; none of the 1,2-cis-glycoside was
detected (Table 1, entries 11-20). The lowest yield
obtained, 54%, was in the glycosylation of octanol (entry
12), which could possibly be due to the formation of the
1,2-cis-glycoside. However, as both anomers of this octyl
glycoside have identical chromatographic mobilities, the
formation of the undesired â-glycoside would have been
readily apparent in the NMR spectrum of the isolated
product; none was detected. The protected disaccharides
25-29 (Scheme 9) were then deprotected using standard
methods to afford oligosaccharides 30-34. Compounds
30 and 33 have been shown to be substrates for myco-
bacterial arabinosyltransferases,5a while 31, 32, and 34
are potential substrates for the same enzymes.
(Scheme 10). D-Glucose, uniformly 13C-enriched at levels
of 99% (35), was converted to the known26 glucal 36 in
85% yield using a convenient one-pot procedure.27 Ozo-
nolysis of the glycal and hydrolysis gave 37 which was
converted to thioglycoside 38 as outlined in Schemes 4
and 8 for the unlabeled parent. Glycosylation of alcohol
11 with 38 provided the disaccharide 39, which was
deacylated to give 40, a labeled analogue of 30.
This approach to 40 is more efficient than the tradi-
tional route which would involve Fisher glycosylation of
99% uniformly enriched D-arabinose and subsequent
conversion to the disaccharide. In addition to being
faster, 99% uniformly labeled D-arabinose is considerably
more expensive than similarly enriched D-glucose. In
addition to its utility in oligosaccharide synthesis, 38
should also be a valuable intermediate in the synthesis
of 13C-labeled arabinonucleosides. An intermediate suit-
able for the preparation of uniformly 13C-enriched ribo-
nucleosides has been recently reported, also starting from
labeled D-glucose.28
Syn th esis of 13C-Labeled Ar abin ofu r an osides. Iso-
topically enriched carbohydrates are of increasing im-
portance in oligosaccharide conformational studies,25 and
the method reported here will be especially useful in
preparing glycans containing labeled arabinofuranosyl
residues. We have used this method for the synthesis of
a disaccharide in which one residue is 13C-enriched
(25) (a) Church, T. J .; Carmichael, I.; Serianni, A. S. J . Am. Chem.
Soc. 1997, 119, 8946 and references therein. (b) Low, D. G.; Probert,
M. A.; Embleton, G.; Seshadri, K.; Field, R. A.; Homans, S. W.;
Windust, J .; Davis, P. J . Glycobiology 1997, 7, 373. (c) Milton, M. J .;
Harris, R.; Probert, M. A.; Field, R. A.; Homans, S. W. Glycobiology
1998, 8, 147.
(26) Wu, R.; Silks, L. A., III Carbohydr. Lett. 1997, 2, 363.
(27) Shull, B. K.; Wu, Z.; Koreeda, M. J . Carbohydr. Chem. 1996,
15, 955.

Pyranose Glycals to Furanose Derivatives
J . Org. Chem., Vol. 63, No. 24, 1998 9041
Sch em e 10a
were evaporated under reduced pressure and below 40 °C
(bath). Solutions of crude products were dried over anhydrous
Na2SO4. Column chromatography was performed on silica gel
60 (40-60 µM). The ratio between silica gel and crude product
ranged from 100:1 to 50:1 (w/w). Optical rotations were
measured at 22 ( 2 °C. 1H NMR spectra were recorded at
300 or 600 MHz, and chemical shifts are referenced to either
TMS (0.0, CDCl3) or HOD (4.78, D2O). 13C NMR spectra were
recorded at 75.5 or 125 MHz, and 13C chemical shifts are
referenced to internal CDCl3 (77.00, CDCl3) or external dioxane
(67.40, D2O). Yields for the glycosylation reactions are given
in Table 1. The assignment of resonances of deprotected
compounds 30-34 was made by two-dimensional homonuclear
and heteronuclear shift correlation experiments. Assignments
of R and S to the protons attached to C5 were made by
comparison of 3J H4,H5 values with those previously reported.32
The 1H NMR spectra of the 13C-labeled compounds (38-40)
were complicated by 13C/1H couplings. However, the proton-
decoupled 13C NMR spectra of these compounds were readily
interpreted by comparison with the spectra of the unlabeled
parents (17, 25, and 30); signal multiplicities due to 13C/13C
coupling were as expected. Elemental analyses were per-
formed by Atlantic Microlab Inc., Norcross, GA. Fast atom
bombardment mass spectra were recorded on samples sus-
pended in Cleland’s matrix using a cesium gun.
Rep r esen ta tive P r oced u r e for Ytter biu m Tr ifla te/
Meth oxy Acetic Acid P r om oted Glycosyla tion s. To a
solution of 6 (84 mg, 0.30 mmol) in dry CH2Cl2 (10 mL) were
added successively 1-octanol (144 µL, 0.91 mmol), methoxy
acetic acid (23 µL, 0.30 mmol), and Yb(OTf)3 (38 mg, 0.06
mmol). The mixture was refluxed for 2.5 h under argon
through a column of activated 4 Å molecular sieves. The
mixture was cooled to room temperature, diluted with CH2-
Cl2, and then washed with a saturated solution of NaHCO3.
The solution was then dried and chromatographed (hexane/
EtOAc, 1:1) to give the product 22 (44 mg, 37%) as a syrup.
R ep r esen t a t ive P r oced u r e for Tr iflic An h yd r id e/
Dip h en yl Su lfoxid e P r om ot ed Glycosyla t ion s. To a
stirred mixture of compound 6 (56 mg, 0.2 mmol) and diphenyl
sulfoxide (115 mg, 0.57 mmol) in a mixture of toluene and CH2-
Cl2 (3:1, 8 mL) at -78 °C was added dropwise triflic anhydride
(48 µL, 0.28 mmol). The reaction mixture was stirred at this
temperature for 20 min and then at -40 °C for 1 h. 2-Chlo-
ropyridine (96 µL, 1.01 mmol) and 10 (113 mg, 0.24 mmol)
were added at -40 °C. The solution was stirred at this
temperature for 1 h, then at 0 °C for 20 min, and finally at
room temperature for 12 h before the addition of excess Et3N
(0.22 mL, 1.58 mmol). The mixture was diluted with CH2Cl2
and washed with saturated solutions of NaHCO3 and NaCl.
The organic phase was dried, filtered, concentrated, and
purified by chromatography (hexane/EtOAc, 1:1) to give 23 (28
mg, 19%) as a syrup.
Rep r esen ta tive P r oced u r e for Th ioglycosid e Glyco-
syla tion s. A mixture of 19 (73 mg, 0.19 mmol), alcohol 12
(77 mg, 0.17 mmol), powdered molecular sieves (4 Å, 0.5 g),
and dry CH2Cl2 (10 mL) was stirred at 0 °C for 20 min. To
the mixture were added N-iodosuccinimide (56 mg, 0.25 mmol)
and silver triflate (15 mg, 0.06 mmol). After being stirred for
2 h, the reaction was quenched with Et3N, and the reaction
mixture was diluted with CH2Cl2 and filtered through Celite.
The filtrate was washed successively with a saturated solution
of Na2S2O3, water, and a saturated NaCl solution. After the
filtrate was dried, the solvent was evaporated, and the residue
was chromatographed (hexanes/EtOAc, 1:1) to yield the dis-
accharide 27 (93 mg, 76%) as a colorless syrup.
a
(a) Reference 27. (b) Scheme 4. (c) Ac2O, H2SO4, 0 °C. (d) CrSH,
BF3OEt2, 0 °C. (e) 11, NIS, AgOTf, CH2Cl2, 0 °C. (f) NaOCH3,
CH3OH.
In conclusion, we have developed a new synthetic route
to protected furanose sugars that can be activated and
converted to oligosaccharides. The formation of pyra-
noses is not a possible side reaction, and therefore this
route has advantages over the usual methods for fura-
noside synthesis. We have demonstrated the utility of
this approach by the preparation of two of the four
possible 2,3,5-tri-O-acetyl-pentofuranoses. The method
should be readily applied to the other isomers by starting
with the appropriate protected glycal. The possibility of
using this route to synthesize a variety of isotopically
enriched arabinofuranosides from glucose is especially
appealing as labeled glucose derivatives are straightfor-
wardly obtained.29 For example, in addition to uniformly
13C-enriched D-glucose, all of the singly 13C-labeled
derivatives are commercially available, as are a host of
deuterated analogues.30 Arabinofuranose residues are
among the most common of all pentofuranoses present
in naturally occurring oligosaccharides, and this meth-
odology will allow rapid access to these derivatives in
both their labeled and unlabeled forms.
Finally, the poor stereocontrol observed with donors
6, 7, 16, and 18 is worthy of mention and further study.
In pyranose systems, a variety of 2-O-acylated glycosyl
donors reliably provide 1,2-trans-glycosides.31 However,
it appears that at least with some furanoses product
ratios in glycosylation reactions are much more sensitive
to the choice of donor and activation method. We are
currently further investigating the use of these and other
glycosylating agents for the synthesis of oligofuranosides.
Exp er im en ta l Section
Gen er a l Meth od s. Solvents were distilled from the ap-
propriate drying agents before use. Unless stated otherwise,
all reactions were carried out at room temperature under a
positive pressure of argon and were monitored by TLC on silica
gel 60 F254 (0.25 mm, E. Merck). Spots were detected under
UV light or by charring with 10% H2SO4 in EtOH. Solvents
Rep r esen ta tive P r oced u r e for P er a ceta te Glycosyla -
tion s. To a stirred solution of 18 (52 mg, 0.16 mmol) in dry
CH3CN (5 mL) was added SnCl4 (19 µL, 0.16 mmol) dropwise
at room temperature. After 20 min, a solution of 10 (55 mg,
0.12 mmol) in CH3CN (3 mL) was added dropwise. After 1 h
of stirring, the mixture was cooled to 0 °C, and a saturated
(28) Agrofoglio, L. A.; J acquinet, J .-C.; Lancelot, G. Tetrahedron Lett.
1997, 38, 1411.
(29) Serianni, A. S.; Vuorinen, T.; Bondo, P. J . Carbohydr. Chem.
1990, 9, 513.
(30) These derivatives are available from Omicron Biochemicals,
South Bend, IN.
(31) Glycoside bond formation has been extensively reviewed: Boons,
G.-J . Contemp. Org. Synth. 1996, 173 and references therein.
(32) (a) Wu, G. D.; Serianni, A. S.; Barker, R. J . Org. Chem. 1983,
48, 1750. (b) Serianni, A. S.; Barker, R. Can. J . Chem. 1979, 57, 3120.

9042 J . Org. Chem., Vol. 63, No. 24, 1998
D’Souza et al.
NaHCO3 solution (2 mL) was added to precipitate tin salts.
The reaction mixture was diluted with CH2Cl2 and filtered
through Celite, and the filtrate was washed with water and a
saturated NaCl solution. After the filtrate was dried and
concentrated, the crude product was purified by chromatog-
raphy (hexane/EtOAc, 3:1) to give 24 (53 mg, 62%) as a
colorless syrup.
p -Cr esyl 2,3,5-Tr i-O-a cet yl-1-t h io-r-D-lyxofu r a n osid e
(19). To a solution of tetraacetate 18 (329 mg, 1.03 mmol) in
dry CH2Cl2 (10 mL) was added p-thiocresol (141 mg, 1.14
mmol). The reaction mixture was cooled to 0 °C, and boron
trifluoride etherate (157 µL, 1.24 mmol) was added dropwise.
After 30 min, Et3N (0.5 mL) was added, and the reaction was
processed as described for the preparation of 17 to give 19 (316
mg, 80%) as a syrup: Rf 0.67 (hexane/EtOAc, 1:1); [R]D +92°
(c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3, δ) 7.41 (d, 2 H, J )
8.1 Hz), 7.14 (d, 2 H, J ) 8.1 Hz), 5.45 (t, 1 H, J ) 4.5 Hz),
5.36 (d, 1 H, J ) 5.9 Hz), 5.27 (dd, 1 H, J ) 4.8, 5.9 Hz), 4.41
(ddd, 1 H, J ) 4.3, 5.5, 6.8 Hz), 4.24 (dd, 1 H, J ) 5.5, 11.5
Hz), 4.20 (dd, 1 H, J ) 6.9, 11.6 Hz), 2.34 (s, 3 H), 2.09 (s, 3
H), 2.06 (s, 6 H); 13C NMR (75.5 MHz, CDCl3, δ) 170.39, 169.44,
169.19, 138.48, 133.51, 129.75, 128.06, 87.74, 76.24, 74.76,
70.88, 61.67, 21.04, 20.62, 20.33, 20.29. Anal. Calcd for
C18H22O7S: C, 56.54; H, 5.80. Found: C, 56.64; H, 5.82.
Meth yl 2,3,5-Tr i-O-a cetyl-r-D-a r a bin ofu r a n osid e (20).
Purification by chromatography (hexane/EtOAc, 1:1) gave the
product. The 1H NMR spectrum of this compound was
identical to that previously reported.34
2,3,5-Tr i-O-a cetyl-D-a r a bin ofu r a n ose (6). A mixture of
glucal 4 (1.28 g, 4.7 mmol), NaHCO3 (40 mg, 0.48 mmol), and
dry CH3OH (0.47 mL) in dry CH2Cl2 (15 mL) was treated with
ozone at -78 °C until the solution became light blue in color.
Dimethyl sulfide (0.69 mL, 9.4 mmol) was added, and the
mixture was warmed to room temperature and stirred for 14
h. The mixture was concentrated, redissolved in CH3OH, and
then filtered. The filtrate was concentrated, redissolved in
CH3OH (10 mL) and acetic acid (15 mL), and then stirred at
70 °C for 14 h. The mixture was cooled to room temperature
and concentrated to dryness. Purification of the residue by
chromatography (hexane/EtOAc, 2:1) gave 6 (935 mg, 72%, 3:2
1
R/â) as a syrup: Rf 0.48 (hexane/EtOAc, 1:2); partial H NMR
(300 MHz, CDCl3, δ) 5.55 (d, J ) 4.4 Hz, H-1â), 5.40 (s, H-1R);
partial 13C NMR (75.5 MHz, CDCl3, δ) 100.49 (C-1R), 94.93
(C-1â).
Meth yl 2,3,5-Tr i-O-acetyl-r-D-lyxofu r an oside (21). Chro-
matography (hexane/EtOAc, 3:1 to 2:1) gave the product as a
colorless syrup: Rf 0.51 (hexane/EtOAc, 1:1); [R]D +89° (c 1.5,
CHCl3); 1H NMR (300 MHz, CDCl3, δ) 5.57 (t, 1 H, J ) 5.5
Hz), 5.21 (dd, 1 H, J ) 1.8, 5.1 Hz), 4.98 (d, 1 H, J ) 1.8 Hz),
4.47 (ddd, 1 H), 4.25 (dd, 1 H, J ) 4.9, 11.7 Hz), 4.19 (dd, 1 H,
2,3,5-Tr i-O-a cetyl-D-lyxofu r a n ose (7). A mixture of ga-
lactal 5 (3.72 g, 13.65 mmol), NaHCO3 (114 mg, 1.36 mmol),
and dry CH3OH (1.4 mL) in dry CH2Cl2 (20 mL) at -78 °C
was treated as described for the preparation of 6 to give 7 (2.34
g, 62%, 2:1 R/â) as a syrup: Rf 0.41 (hexane/EtOAc, 1:2); partial
1H NMR (300 MHz, CDCl3, δ) 5.45 (d, J ) 2.3 Hz, H-1R), 5.43
(d, J ) 4.8 Hz, H-1â); partial 13C NMR (75.5 MHz, CDCl3, δ)
99.28 (C-1R), 94.77 (C-1â).
1,2,3,5-Tetr a -O-a cetyl-D-a r a bin ofu r a n ose (16). To a
stirred solution of triacetate 6 (527 mg, 1.91 mmol) in acetic
anhydride (10 mL) at 0 °C was added, dropwise, dilute H2SO4
(100 µL of H2SO4 dissolved in 1 mL of Ac2O). After 1 h, the
reaction was quenched by adding CH2Cl2 and a saturated
solution of NaHCO3, and stirring was continued for 10 min.
The mixture was diluted with additional CH2Cl2 and washed
with a saturated solution of NaHCO3, water, and a saturated
NaCl solution. The organic layer was dried and filtered, and
the filtrate was concentrated in vacuo to give 16 (599 mg, 99%)
as a syrup. The 1H NMR spectrum of this compound was
identical to that previously reported.33
J ) 7.3, 11.6 Hz), 3.40 (s, 3 H), 2.08 (s, 3 H), 2.07 (s, 6 H); 13
C
NMR (75.5 MHz, CDCl3, δ) 170.46, 169.44, 169.27, 105.49,
75.29, 75.21, 71.02, 62.72, 55.44, 20.64, 20.37, 20.25. Anal.
Calcd for C12H18O8: C, 49.65; H, 6.25. Found: C, 49.68; H,
6.23.
Octyl 2,3,5-Tr i-O-a cetyl-r-D-a r a bin ofu r a n osid e (22).
Purification by chromatography (hexane/EtOAc, 2:1) gave the
product as a colorless syrup: Rf 0.57 (hexane/EtOAc, 2:1); [R]D
1
+60° (c 0.5, CHCl3); H NMR (300 MHz, CDCl3, δ) 5.07 (d, 1
H, J ) 1.6 Hz), 5.01 (s, 1 H), 4.97 (dd, 1 H, J ) 1.4, 4.7 Hz),
4.42 (m, 1 H), 4.22 (m, 2 H), 3.68 (dt, 1 H, J ) 6.8, 9.6 Hz),
3.44 (dt, 1 H, J ) 6.8, 9.6 Hz), 2.10 (s, 6 H), 2.09 (s, 3 H), 1.58
(m, 2 H), 1.36-1.27 (m, 10 H), 0.88 (t, 3 H, J ) 6.9 Hz); 13C
NMR (75.5 MHz, CDCl3, δ) 170.41, 169.99, 169.47, 105.41,
81.18, 80.01, 77.11, 67.49, 63.22, 31.64, 29.22, 29.13, 29.08,
25.85, 22.48, 20.59, 20.55, 13.90. Anal. Calcd for C19H32O8:
C, 58.75; H, 8.30. Found: C, 58.70; H, 8.21.
p-Cr esyl 2,3,5-Tr i-O-a cetyl-1-th io-r-D-a r a bin ofu r a n o-
sid e (17). Tetraacetate 16 (8.5 g, 25 mmol) was dissolved in
dry CH2Cl2 (50 mL) and cooled to 0 °C before p-thiocresol (3.72
g, 30 mmol) was added. After the mixture was stirred for 20
min under argon, boron trifluoride etherate (17.7 g, 125 mmol)
was added via syringe. The mixture was neutralized after 15
min with Et3N (18 mL, 125 mmol), diluted with CH2Cl2, and
then washed with water and a saturated NaCl solution. The
solution was dried and evaporated, and the crude product was
purified by column chromatography (toluene/EtOAc, 4:1) to
give 17 (8.4 g, 88%) as a clear syrup: Rf 0.4 (toluene/EtOAc,
Meth yl 6-O-(2,3,5-Tr i-O-a cetyl-r-D-a r a bin ofu r a n osyl)-
2,3,4-tr i-O-ben zyl-r-D-glu cop yr a n osid e (23). Chromatog-
raphy (hexane/EtOAc, 1:1) gave the product as a colorless
syrup: Rf 0.52 (hexane/EtOAc, 1:1); [R]D +50° (c 1.1, CHCl3);
1H NMR (300 MHz, CDCl3, δ) 7.26-7.36 (m, 15 H), 5.14 (m, 2
H), 4.99 (d, 1 H, J ) 10.8 Hz), 4.96 (dd, 1 H, J ) 1.4, 4.6 Hz),
4.89 (d, 1 H, J ) 10.8 Hz), 4.81 (d, 1 H, J ) 10.9 Hz), 4.80 (d,
1 H, J ) 12.1 Hz), 4.67 (d, 1 H, J ) 12.4 Hz), 4.63 (d, 1 H, J
) 11.1 Hz), 4.60 (d, 1 H, J ) 3.7 Hz), 4.34 (dd, 1 H, J ) 3.0,
11.2 Hz), 4.20 (m, 1 H), 4.14 (dd, 1 H, J ) 5.7, 11.3 Hz), 4.0
(dd, 1 H, J ) 3.6, 11.2 Hz), 3.9 (t, 1 H, J ) 9.4 Hz), 3.75 (ddd,
1 H, J ) 1.7, 3.6, 9.9 Hz), 3.68 (dd, 1 H, J ) 1.7, 11.1 Hz), 3.59
(t, 1 H, J ) 9.0 Hz), 3.55 (dd, 1 H, J ) 3.5, 9.6 Hz), 3.37 (s, 3
H), 2.08 (s, 3 H), 2.02 (s, 6 H); 13C NMR (75.5 MHz, CDCl3, δ)
170.45, 169.91, 169.29, 138.64, 138.14, 138.04, 128.37, 128.30,
128.02, 127.86, 127.81, 127.71, 127.57, 127.52, 105.88, 97.98,
81.88, 80.99, 80.53, 79.84, 77.59, 77.05, 75.65, 74.85, 73.29,
69.67, 65.91, 63.18, 55.04, 20.63, 20.61. Anal. Calcd for
1
4:1); [R]D +117.6° (c 1.8, CHCl3); H NMR (300 MHz, CDCl3,
δ) 7.41-7.35 (d, 2 H), 7.13-7.10 (d, 2 H), 5.47 (d, 1 H, J ) 2.3
Hz), 5.26 (t, 1 H, J ) 2.3, 2.1 Hz), 5.06 (ddd, 1 H, J ) 2.3, 6.6,
0.4 Hz), 4.48 (ddd, 1 H, J ) 6.6, 3.7, 5.2 Hz), 4.41 (dd, 1 H, J
) 11.9, 3.7 Hz), 4.26 (dd, 1 H, J ) 11.9, 5.4 Hz), 2.32 (s, 3 H),
2.17, 2.15, 2.06 (3s, 9 H); 13C NMR (75.5 MHz, CDCl3, δ)
170.43, 169.90, 169.48, 138.02, 132.67, 129.7, 91.16, 81.43,
79.92, 77.19, 62.83, 20.72. Anal. Calcd for C18H22O7S: C,
56.53; H, 5.80. Found: C, 56.67; H, 5.78.
C
39H46O13: C, 64.81; H, 6.41. Found: C, 64.64; H, 6.35.
Meth yl 6-O-(2,3,5-Tr i-O-a cetyl-r-D-lyxofu r a n osyl)-2,3,4-
1,2,3,5-Tetr a -O-a cetyl-D-lyxofu r a n ose (18). To a solution
of triacetate 7 (517 mg, 1.87 mmol) in acetic anhydride (10
mL) at 0 °C was added, dropwise, dilute H2SO4 (100 µL of
H2SO4 dissolved in 1 mL of Ac2O). After 1 h of stirring,
the reaction was worked-up as described for the preparation
of 16 to give 18 (590 mg, 99%) as a syrup. The 1H NMR
spectrum of this compound was identical to that previously
reported.33
tr i-O-ben zyl-r-D-glu cop yr a n osid e (24). Chromatography
(hexane/EtOAc, 3:1 to 1:1) gave the product as a syrup: Rf
1
0.46 (hexane/EtOAc, 1:1); [R]D +62° (c 1.4, CHCl3); H NMR
(300 MHz, CDCl3, δ) 7.35-7.26 (m, 15 H), 5.57 (t, 1 H, J ) 5.6
Hz), 5.26 (dd, 1 H, J ) 1.7, 5.1 Hz), 5.17 (d, 1 H, J ) 1.7 Hz),
4.99 (d, 1 H, J ) 10.9 Hz), 4.89 (d, 1 H, J ) 10.7 Hz), 4.82 (d,
1 H, J ) 10.9 Hz), 4.80 (d, 1 H, J ) 12.1 Hz), 4.66 (d, 1 H, J
) 12.1 Hz), 4.61 (d, 1 H, J ) 10.4 Hz), 4.58 (d, 1 H, J ) 3.2
(33) Kam, B. L.; Barascut, J .-L.; Imbach, J .-L. Carbohydr. Res. 1979,
69, 135.
(34) Bock, K.; Pedersen, C. Carbohydr. Res. 1973, 29, 331.

Pyranose Glycals to Furanose Derivatives
J . Org. Chem., Vol. 63, No. 24, 1998 9043
Hz), 4.43 (ddd, 1 H, J ) 4.7, 5.9, 7.4 Hz), 4.20 (dd, 1 H, J )
4.7, 11.7 Hz), 4.12 (dd, 1 H, J ) 7.4, 11.7 Hz), 4.02-3.95 (m,
2 H), 3.75-3.66 (m, 2 H), 3.55-3.49 (m, 2 H), 3.36 (s, 3 H),
2.06 (s, 3 H), 2.05 (s, 3 H), 1.96 (s, 3 H); 13C NMR (75.5 MHz,
CDCl3, δ) 170.46, 169.41, 169.18, 138.64, 138.11, 138.04,
128.37, 128.34, 128.30, 127.08, 127.82, 127.76, 127.69, 127.49,
104.71, 98.02, 81.88, 79.79, 77.42, 75.63, 75.38, 74.94, 73.35,
70.96, 69.71, 66.52, 62.80, 55.10, 20.57, 20.44, 20.31. Anal.
Calcd for C39H46O13: C, 64.81; H, 6.41. Found: C, 64.56; H,
6.39.
Meth yl 5-O-(2,3,5-Tr i-O-a cetyl-r-D-a r a bin ofu r a n osyl)-
2,3-d i-O-ben zoyl-r-D-a r a bin ofu r a n osid e (25). Chromatog-
raphy (toluene/EtOAc, 9:1) yielded the product as a clear
syrup: Rf 0.18 (toluene/EtOAc, 9:1); [R]D +19.2° (c 3.7, CHCl3);
1H NMR (300 MHz, CDCl3, δ) 8.11-7.26 (m, 10 H), 5.61 (d, 1
H, J ) 4.8 Hz), 5.49 (s, 1 H), 5.22 (s, 1 H), 5.21 (s, 1 H), 5.14
(s, 1 H), 4.94 (d, 1 H, J ) 4.5 Hz), 4.48-4.33 (m, 3 H), 4.22
(dd, 1 H, J ) 5.4, 11.4 Hz), 4.12 (dd, 1 H, J ) 3.3, 10.5 Hz),
3.85 (d, 1 H, J ) 12 Hz), 3.47 (s, 3 H), 2.09, 2.07, 1.87 (3s, 9
H); 13C NMR (75.5 MHz, CDCl3, δ) 170.61, 170.31, 169.41,
165.72, 165.49, 133.60, 133.48, 129.94, 129.90, 129.28, 129.22,
128.60, 128.50, 106.83, 105.45, 82.19, 81.49, 81.14, 80.90,
77.37, 76.99, 65.42, 63.31, 54.92, 20.80, 20.76, 20.47. Anal.
Calcd C31H34O14: C, 57.40; H, 5.61. Found: C, 57.74; H, 5.49.
Anal. Calcd for C40H48O13Si: C, 62.81; H, 6.32. Found: C,
62.94; H, 6.46.
Meth yl 3-O-(2,3,5-Tr i-O-a cetyl-r-D-lyxofu r a n osyl)-5-O-
ter t-bu tyld ip h en ylsilyl-2-O-ben zoyl-r-D-a r a bin ofu r a n o-
sid e (29). Purification by chromatography (hexane/EtOAc,
2:1) gave the product as a colorless syrup: Rf 0.41 (hexane/
1
EtOAc, 2:1); [R]D +62.0° (c 1.1, CHCl3); H NMR (300 MHz,
CDCl3, δ) 7.99 (m, 2 H), 7.70 (m, 4 H), 7.57 (m, 1 H), 7.43-
7.32 (m, 8 H), 5.56 (t, 1 H, J ) 5.5 Hz), 5.43 (d, 1 H, J ) 1.6
Hz), 5.30 (dd, 1 H, J ) 1.7, 5.2 Hz), 5.24 (d, 1 H, J ) 1.2 Hz),
5.09 (s, 1 H), 4.39 (m, 1 H), 4.24-4.11 (m, 3 H), 4.03 (dd, 1 H,
J ) 7.3, 11.5 Hz), 3.94 (dd, 1 H, J ) 4.7, 11.3 Hz), 3.87 (dd, 1
H, J ) 3.6, 11.3 Hz), 3.44 (s, 3 H), 2.09 (s, 3 H), 2.07 (s, 3 H),
1.90 (s, 3 H), 1.03 (s, 9 H); 13C NMR (75.5 MHz, CDCl3, δ)
170.33, 169.36, 169.20, 165.49, 135.54, 135.49, 133.26, 133.23,
129.74, 129.60, 129.57, 129.20, 128.28, 127.59, 127.54, 106.84,
103.77, 83.26, 82.63, 80.80, 75.40, 75.33, 70.79, 62.91, 62.50,
54.53, 26.62, 20.48, 20.39, 20.27, 19.20. Anal. Calcd for
C
40H48O12Si‚0.5H2O: C, 62.07; H, 6.31. Found: C, 62.13; H,
6.21.
Meth yl r-D-Ar a bin ofu r a n osyl-(1f5)-r-D-a r a bin ofu r a -
n osid e (30). Disaccharide 25 (160 mg, 0.25 mmol) dissolved
in dry CH3OH (5 mL) was treated with a catalytic amount of
sodium methoxide. The mixture was stirred for 4 h and then
neutralized with prewashed Amberlite IR-118 (H+) resin. The
solution was filtered, and the resulting residue was taken up
in CH2Cl2. The product was extracted into water, and the
water layer was concentrated. Purification by column chro-
matography (CHCl3/CH3OH, 3:1) yielded 30 (67 mg, 90%) as
a clear syrup: [R]D -157° (c 1.6, H2O); Rf 0.7 (CHCl3/CH3OH,
2:1); 1H NMR (600 MHz, D2O, δ) 4.99 (d, 1 H, J ) 1.5 Hz,
H-1′), 4.85 (d, 1 H, J ) 1.5 Hz, H-1), 4.08 (ddd, 1 H, J ) 5.5,
3.4, 5.8 Hz, H-4), 4.04 (dd, 1 H, J ) 1.3, 3.1 Hz, H-2′), 4.01
(ddd, 1 H, J ) 5.5, 3.4, 6.1 Hz, H-4′), 3.98 (dd, 1 H, J ) 1.5,
3.1 Hz, H-2), 3.92 (dd, 1 H, J ) 3.1, 5.8 Hz, H-3), 3.87 (dd, 1
H, J ) 3.1, 6.1 Hz, H-3′), 3.80 (dd, 1 H, J ) 5.5, 11.3 Hz, H-5R),
3.74 (dd, 1 H, J ) 3.4, 12.5 Hz, H-5′S), 3.72 (dd, 1 H, J ) 3.4,
11.3 Hz, H-5S), 3.63 (dd, 1 H, J ) 5.5, 12.5 Hz, H-5′R), 3.34
(s, 3 H, OCH3); 13C NMR (125 MHz, D2O, δ) 109.31 (C-1),
108.31 (C-1′), 84.87 (C-4′), 83.14 (C-4), 81.79 (C-2′), 81.49 (C-
2′), 77.46 (C-3), 77.43 (C-3′), 67.73 (C-5), 62.08 (C-5′), 55.88
(OCH3) HR-FABMS m/z calcd for [C11H20O9]H+ 297.1185,
found 297.1174.
Meth yl 5-O-(2,3,5-Tr i-O-a cetyl-r-D-lyxofu r a n osyl)-2,3-
d i-O-ben zoyl-r-D-a r a bin ofu r a n osid e (26). Chromatogra-
phy (hexane/EtOAc, 1:1) gave the product as a syrup: Rf 0.44
1
(hexane/EtOAc, 1:1); [R]D +26° (c 1.6, CHCl3); H NMR (300
MHz, CDCl3, δ) 8.07-7.40 (m, 10 H), 5.57 (t, 1 H, J ) 5.6 Hz),
5.45 (m, 2 H), 5.31 (dd, 1 H, J ) 1.5, 5.2 Hz), 5.21 (d, 1 H, J
) 1.2 Hz), 5.13 (s, 1 H), 4.53 (m, 1 H), 4.37 (m, 1 H), 4.23 (dd,
1 H, J ) 4.9, 11.7 Hz), 4.19 (dd, 1 H, J ) 4.4, 11.8 Hz), 4.11
(dd, 1 H, J ) 4.8, 11.1 Hz), 3.90 (dd, 1 H, J ) 3.2, 11.2 Hz),
3.47 (s, 3 H), 2.05 (s, 6 H), 2.03 (s, 3 H); 13C NMR (75.5 MHz,
CDCl3, δ) 170.48, 169.30, 169.16, 165.60, 165.35, 133.44,
133.35, 129.80, 129.72, 129.11, 128.99, 128.50, 128.36, 106.76,
104.69, 81.95, 81.35, 77.37, 75.46, 75.42, 70.94, 66.93, 62.63,
54.88, 20.65, 20.38, 20.26. Anal. Calcd for C31H34O14‚H2O: C,
57.41; H, 5.59. Found: C, 57.13; H, 5.24.
Octyl 5-O-(2,3,5-Tr i-O-a cetyl-r-D-lyxofu r a n osyl)-2,3-d i-
O-ben zyl-r-D-a r a bin ofu r a n osid e (27). Chromatography
(hexane/EtOAc, 1:1) gave the product as a colorless syrup: Rf
1
0.71 (hexane/EtOAc, 1:1); [R]D +83° (c 1.3, CHCl3); H NMR
Meth yl r-D-Lyxofu r a n osyl-(1f5)-r-D-a r a bin ofu r a n o-
sid e (31). Disaccharide 18 (55 mg, 0.09 mmol) was dissolved
in dry CH3OH (5 mL), and then 0.1 M methanolic NaOCH3
(0.5 mL) was added dropwise. After 4 h, the reaction mixture
was neutralized with Amberlite IR-118 (H+) resin, filtered, and
evaporated, and the residue was chromatographed (CHCl3/
CH3OH, 2:1) to give 31 (18 mg 69%) as a syrup: Rf 0.56
(CHCl3/CH3OH, 2:1); [R]D +136° (c 1.1, H2O); 1H NMR (300
MHz, D2O, δ) 4.97 (d, 1 H, J ) 3.2 Hz, H-1′), 4.80 (d, 1 H, J )
1.1 Hz, H-1), 4.26 (t, 1 H, J ) 4.6 Hz, H-3′), 4.17 (td, 1 H, J )
4.3, 6.6 Hz, H-4′), 4.05 (dd, 1 H, J ) 3.3, 4.8 Hz, H-2′), 4.01
(dt, 1 H, J ) 3.4, 5.7 Hz, H-4), 3.93 (dd, 1 H, J ) 1.7, 3.3 Hz,
H-2), 3.85 (dd, 1 H, J 3.3, 5.8 Hz, H-3), 3.75 (dd, 1 H, J ) 5.6,
11.4 Hz, H-5R), 3.71 (dd, 1 H, J ) 4.2, 11.9 Hz, H-5′S), 3.67
(dd, 1 H, J ) 3.1, 10.9 Hz, H-5S), 3.62 (dd, 1 H, J ) 6.6, 11.9
Hz, H-5′R), 3.28 (s, 3 H, OCH3); 13C NMR (75.5 MHz, D2O, δ)
108.38 (C-1), 107.13 (C-1′), 82.21 (C-4), 80.69 (C-2), 80.39 (C-
4′), 76.54 (C-3), 75.95 (C-2′), 71.03 (C-3′), 67.59 (C-5), 60.19
(C-5′), 55.03 (OCH3). HR-FABMS m/z calcd for [C11H20O9]-
Na+ 319.1005, found 319.0996.
(300 MHz, CDCl3, δ) 7.36-7.26 (m, 10 H), 5.54 (t, 1 H, J ) 5.6
Hz), 5.25 (dd, 1 H, J ) 1.7, 5.1 Hz), 5.13 (d, 1 H, J ) 1.6 Hz),
5.01 (d, 1 H, J ) 1.0 Hz), 4.59 (d, 2 H, J ) 11.9 Hz), 4.50 (d,
1 H, J ) 11.9 Hz), 4.49 (d, 1 H, J ) 11.9 Hz), 4.41 (ddd, 1 H,
J ) 4.8, 6.0, 7.3 Hz), 4.21 (dd, 1 H, J ) 4.7, 11.7 Hz), 4.15 (dd,
1 H, J ) 7.4, 11.5 Hz), 4.13 (ddd, 1 H, J ) 3.5, 4.6, 7.1 Hz),
4.01 (dd, 1 H, J ) 1.4, 3.5 Hz), 3.88 (dd, 1 H, J ) 3.4, 6.9 Hz),
3.83 (dd, 1 H, J ) 4.8, 11.2 Hz), 3.70 (dt, 1 H, J ) 6.7, 9.6 Hz),
3.66 (dd, 1 H, J ) 3.5, 11.2 Hz), 3.38 (dt, 1 H J ) 6.6, 9.6 Hz),
2.06 (s, 3 H), 2.05 (s, 6 H), 1.61-1.55 (m, 2 H), 1.33-1.27 (m,
10 H), 0.88 (t, 3 H, J ) 6.9 Hz); 13C NMR (75.5 MHz, CDCl3,
δ) 170.49, 169.38, 169.18, 137.74, 137.46, 128.33, 128.29,
127.83, 127.75, 127.67, 105.98, 104.62, 88.16, 83.14, 79.7,
75.30, 75.24, 72.06, 71.90, 70.98, 67.65, 67.20, 62.78, 31.73,
29.41, 29.27, 29.17, 26.02, 22.55, 20.68, 20.40, 20.29, 14.00.
Anal. Calcd for C38H52O12: C, 65.13; H, 7.48. Found: C, 64.96;
H, 7.44.
Meth yl 3-O-(2,3,5-Tr i-O-a cetyl-r-D-a r a bin ofu r a n osyl)-
5-O-ter t-bu tyld ip h en ylsilyl-2-O-ben zoyl-r-D-a r a bin ofu r a -
n osid e (28). Chromatography (hexane/EtOAc, 9:1) gave 11
(477 mg, 79%) as a syrup: Rf 0.35 (hexane/EtOAc, 6:1); [R]D
+20.3° (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3, δ) 7.99-
7.97 (m, 2 H), 7.70-7.53 (m, 4 H), 7.42-7.26 (m, 7 H), 5.40 (s,
1 H), 5.30 (d, 1 H, J ) 1.2 Hz), 5.18 (d, 1 H, J ) 1.6 Hz), 5.09
(s, 1 H), 4.97 (dd, 1 H, J ) 1.6, 5.1 Hz), 4.46 (m, 1 H), 4.26-
4.04 (m, 4 H), 3.89-3.87 (m, 2 H), 3.44 (s, 3 H), 2.10 (s, 3 H),
2.08 (s, 3 H), 1.96 (s, 3 H), 1.03 (s, 9 H); 13C NMR (75.5 MHz,
CDCl3, δ) 170.49, 170.01, 169.48, 165.59, 135.64, 135.59,
133.36, 133.29, 129.87, 129.77, 129.70, 129.34, 128.39, 127.72,
127.66, 127.27, 107.14, 104.81, 84.94, 83.21, 82.60, 81.19,
80.47, 79.97, 77.22, 63.05, 62.94, 54.74, 26.74, 20.75, 19.33.
Octyl r-D-Lyxofu r a n osyl-(1f5)-r-D-a r a bin ofu r a n osid e
(32). A solution of 21 (66 mg, 0.09 mmol) in dry CH3OH (5
mL) was hydrogenated over 10% Pd/C (25 mg) under a flow of
H2 for 4 h. The catalyst was filtered off, and the filtrate was
concentrated. A solution of the residue in dry CH3OH (5 mL)
was stirred with 0.1 M methanolic sodium methoxide (0.5 mL)
for 2 h. Neutralization with prewashed Amberlite IR-118 (H+)
resin followed by filtration and concentration gave a residue
that was purified by chromatography (CHCl3/CH3OH, 3:1) to
yield 32 (31 mg, 84%) as a syrup: Rf 0.73 (CHCl3/CH3OH, 3:1);
1
[R]D +85° (c 1.0, H2O); H NMR (300 MHz, D2O, δ) 4.95 (d, 1
H, J ) 2.8 Hz, H-1′), 4.82 (d, 1 H, J ) 1.6 Hz, H-1), 4.29 (t, 1

9044 J . Org. Chem., Vol. 63, No. 24, 1998
D’Souza et al.
H, J ) 4.8 Hz, H-3′), 4.15 (td, 1 H, J ) 4.4, 6.1 Hz, H-4′), 4.04
(dd, 1 H, J ) 2.8, 4.9 Hz, H-2′), 3.97 (m, 1 H, H-4), 3.93 (dd, 1
H, J ) 1.6, 3.8 Hz, H-2), 3.87 (dd, 1 H, J ) 3.7, 6.5 Hz, H-3),
3.76 (dd, 1 H, J ) 4.6, 11.3 Hz, H-5S), 3.71 (dd, 1 H, J ) 4.2,
11.8 Hz, H-5′S), 3.66-3.55 (m, 3 H, H-5R, 5′R, OCH2), 3.34
(dt, 1 H, J ) 6.8, 9.2 Hz, OCH2), 1.48 (m, 2 H, OCH2CH2),
1.18 (m, 10 H, octyl CH2), 0.76 (t, 3 H, J ) 6.8 Hz, octyl CH3);
13C NMR (75.5 MHz, D2O, δ) 107.41 (C-1), 107.15 (C-1′), 81.74
(C-4), 81.47 (C-2), 80.18 (C-4′), 76.81 (C-3), 75.82 (C-2′), 71.02
(C-3′), 68.26 (C-5), 67.10 (octyl C1), 60.17 (C-5′), 31.84 (octyl
C2), 29.39, 29.27, 25.94, 22.60 (octyl C3-C7), 13.82 (octyl CH3).
HR-FABMS m/z calcd for [C18H34O9]Na+ 417.2105, found
417.2104.
H-3′), 4.07 (td, 1 H, J ) 4.1, 6.8 Hz, H-4′), 4.02 (dd, 1 H, J )
1.1, 2.1 Hz, H-2), 3.98 (dd, 1 H, J ) 3.2, 4.9 Hz, H-2′), 3.93
(dt, 1 H, J ) 3.4, 5.6 Hz, H-4), 3.82 (dd, 1 H, J ) 1.8, 5.2 Hz,
H-3), 3.68 (dd, 1 H, J ) 3.4, 12.2 Hz, H-5S), 3.65 (dd, 1 H, J
) 4.3, 12.0 Hz, H-5′S), 3.57 (dd, 1 H, J ) 5.8, 12.3 Hz, H-5R),
3.56 (dd, 1 H, J ) 6.6, 12.3 Hz, H-5′R), 3.23 (s, 3 H, OCH3);
13C NMR (75.5 MHz, D2O, δ) 108.41 (C-1), 106.76 (C-1′), 83.32
(C-4), 82.72 (C-3), 80.41 (C-4′), 79.05 (C-2), 76.04 (C-2′), 70.96
(C-3′), 61.03 (C-5), 60.16 (C-5′), 54.71 (OCH3). HR-FABMS
m/z calcd for [C11H20O9]Na+ 319.1005, found 319.1028.
p-Cr esyl 2,3,5-Tr i-O-a cetyl-1-th io-r-D-[U-13C5]-a r a bin o-
fu r a n osid e (38). The chromatographic properties of this
compound were identical to those of its unlabeled parent 17:
13C NMR (75.5 MHz, CDCl3, δ) 91.04 (dt, J ) 2.6, 41.1 Hz),
81.31 (t, J ) 43.2 Hz), 79.81 (ddd, J ) 3.1, 39.6, 43.4 Hz), 77.01
(ddd, J ) 1.8, 39.5, 41.4 Hz), 62.70 (d, J ) 44.3 Hz).
Meth yl r-D-Ar a bin ofu r a n osyl-(1f3)-r-D-a r a bin ofu r a -
n osid e (33). A solution of disaccharide 28 (300 mg, 0.39
mmol) dissolved in dry THF (3 mL) was cooled to 0 °C and
then treated with TBAF (0.5 mL, 1 M solution in THF). After
1 h, the reaction mixture was taken up in CH2Cl2, and the
organic layer was washed with aqueous solutions of am-
monium sulfate and saturated NaCl before being dried and
concentrated. The mixture was taken up in CH3OH (5 mL)
and treated with a catalytic amount of sodium methoxide for
1 h. The mixture was then neutralized with Amberlite IR-
118 (H+) resin, filtered, evaporated, and purified by chroma-
tography (CHCl3/CH3OH, 3:1) to yield 33 (93 mg, 81%) as a
clear syrup: Rf 0.33 (CHCl3/CH3OH, 3:1); [R]D +148.3° (c 0.9,
Meth yl 2,3,5-Tr i-O-a cetyl-r-D-[U-13C5]-a r a bin ofu r a n o-
syl-(1f5)-2,3-di-O-ben zoyl-r-D-ar abin ofu r an oside (39). The
chromatographic properties of this compound were identical
to those of its unlabeled parent 25: 13C NMR (75.5 MHz,
CDCl3, δ) 170.50, 170.20, 169.29, 165.58, 165.36, 133.49,
133.36, 129.80, 129.77, 129.13, 129.06, 128.47, 128.36, 106.60,
105.28 (d, J ) 48.6 Hz), 82.04, 81.36, 81.01 (ddd, J ) 1.8, 37.1,
42.8 Hz), 80.75 (t, J ) 46.9 Hz), 77.06 (dd, J ) 39.3, 44.4 Hz),
76.83, 65.21, 63.17 (d, J ) 44.7), 65.21, 63.17 (d, J ) 44.7 Hz),
54.80, 20.68, 20.64, 20.35.
1
H2O); H NMR (600 MHz, D2O, δ) 5.07 (d, 1 H, J ) 1.6 Hz,
Meth yl [U-13C5]-Ar a bin ofu r a n osyl-(1f5)-r-D-a r a bin o-
fu r a n osid e (40). The chromatographic properties of this
compound were identical to those of its unlabeled parent 30:
13C NMR (75.5 MHz, D2O, δ) 108.47, 107.46 (d, J ) 47.3 Hz),
84.01 (ddd, J ) 3.0, 39.2, 42.2 Hz), 82.32 (d, J ) 2.2 Hz), 80.94
(dd, J ) 40.8, 46.8 Hz), 80.64, 76.56, 76.52 (t, J ) 39.2 Hz),
66.90, 61.21 (d, J ) 42.4 Hz), 55.04. HR-FABMS calcd for
[12C613C5H20O9]Na+ 324.1173, found 324.1219.
H-1′), 4.88 (d, 1 H, J ) 1.2 Hz, H-1), 4.29 (dd, 1 H, J ) 1.3, 2.0
Hz, H-2), 4.06 (ddd, 1 H, J ) 5.5, 3.4, 5.8 Hz, H-4), 4.03 (dd,
1 H, J ) 1.6, 3.4 Hz, H-2′), 3.95-3.99 (m, 2 H, H-3, H-4), 3.86
(dd, 1 H, J ) 3.4, 6.2 Hz, H-3′), 3.78 (dd, 1 H, J ) 3.4, 12.5
Hz, H-5S), 3.72 (dd, 1 H, J ) 3.4, 12.1 Hz, H-5′S), 3.68 (dd, 1
H, J ) 5.8, 12.5 Hz, H-5R), 3.63 (dd, 1 H, J ) 5.8, 12.1 Hz,
H-5′R), 3.34 (s, 3 H, OCH3); 13C NMR (125 MHz, D2O, δ) 109.34
(C-1), 107.94 (C-1′), 84.77 (C-4′), 84.02 (C-4), 82.98 (C-3), 82.04
(C-2′), 79.96 (C-2), 77.43 (C-3′), 62.03 (C-5), 61.95 (C-5′), 55.65
(OCH3). HR-FABMS m/z calcd for [C11H20O9]Na+ 319.1005,
found 319.1012.
Ack n ow led gm en t. This work was supported by The
Ohio State University and the NSF REU (P.E.C.) and
GAANN (J .D.A.) programs. Acknowledgment is made
to the donors of the Petroleum Research Fund, admin-
istered by the American Chemical Society, for partial
support of this research. We thank Dr. Charles Cottrell
for the high-field NMR spectra.
Meth yl r-D-Lyxofu r a n osyl-(1f3)-r-D-a r a bin ofu r a n o-
sid e (34). A solution of 29 (79 mg, 0.11 mmol) in dry THF (5
mL) at 0 °C was stirred with TBAF (1.0 M solution in THF,
0.5 mL). After 3 h, the solvent was removed under reduced
pressure. The residue was dissolved in dry CH3OH (3 mL)
and treated with 0.1 M sodium methoxide (0.5 mL) for 2 h at
room temperature. The pH of the solution was adjusted to
7.0 by addition of Amberlite IR-118 (H+) resin, and the filtrate
obtained upon removal of the resin was evaporated to dryness.
Chromatography of the residue (CHCl3/CH3OH, 2:1) gave 34
(24 mg, 77%) as a syrup: Rf 0.24 (CHCl3/CH3OH, 2:1); [R]D
+103.0° (c 0.8, H2O); 1H NMR (300 MHz, D2O, δ) 4.99 (d, 1 H,
J ) 3.1 Hz, H-1′), 4.77 (s, 1 H, H-1), 4.19 (t, 1 H, J ) 4.6 Hz,
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C spectra
for compounds 26, 29-34, and 40 (16 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from ACS; see any current masthead page for ordering
information.
J O9815406