Synthesis of four ester protected thiofuranose sugars

Article abstract of DOI:10.1081/SCC-100108233

The products obtained by titanium tetrachloride mediated dithioacetalization of four pentofuranoside derivatives were converted to thiofuranose sugars, either by direct cyclization via the unstable trifiate intermediate, or by treatment of the derived mesylate. A facile inversion of a D-ribose dibenzyl dithioacetal 9 to an L-lyxose dibenzyl dithioacetal 12 via hydrolysis of the Mitsunobu derived formate intermediate is also described.

Full text of DOI:10.1081/SCC-100108233

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
SYNTHESIS OF FOUR ESTER PROTECTED
THIOFURANOSE SUGARS
Ian Birtwistle , Peter Maddocks , John M. O'Callaghan & John Warren
To cite this article: Ian Birtwistle , Peter Maddocks , John M. O'Callaghan & John Warren (2001)
SYNTHESIS OF FOUR ESTER PROTECTED THIOFURANOSE SUGARS, Synthetic Communications,
31:24, 3829-3838, DOI: 10.1081/SCC-100108233
To link to this article: http://dx.doi.org/10.1081/SCC-100108233
Published online: 09 Nov 2006.
Submit your article to this journal
Article views: 26
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [Library Services City University London]
Date: 04 April 2016, At: 00:48

SYNTHETIC COMMUNICATIONS, 31(24), 3829–3838 (2001)
SYNTHESIS OF FOUR ESTER
PROTECTED THIOFURANOSE SUGARS
Ian Birtwistle, Peter Maddocks,*
John M. O’Callaghan, and John Warren
Chemical Development Division, GlaxoSmithKline Ltd.,
Temple Hill, Dartford, Kent, DA1 5AH, UK
ABSTRACT
The products obtained by titanium tetrachloride mediated
dithioacetalization of four pentofuranoside derivatives were
converted to thiofuranose sugars, either by direct cyclization
via the unstable triflate intermediate, or by treatment of the
derived mesylate. A facile inversion of a D-ribose dibenzyl
dithioacetal 9 to an L-lyxose dibenzyl dithioacetal 12 via hydro-
lysis of the Mitsunobu derived formate intermediate is also
described.
INTRODUCTION
A variety of methods have been reported in the literature for the syn-
thesis of thiofuranose sugars,1–7 in which the hydroxyls are protected by
ester groups. In the synthesis of benzyl-2-deoxy-3,5-di-O-p-toluoyl-1,4-
dithio-D-erythro-pentofuranoside, reported by Dyson et al.,3 benzyl ether
*Corresponding author.
3829
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

ORDER
REPRINTS
3830
BIRTWISTLE ET AL.
protection was used throughout, and after a subsequent debenzylation pro-
cedure using boron trichloride at low temperature, esterification was
achieved at the end of the reaction sequence. Bredenkamp et al.4,5 describe
the synthesis of 1-thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-D-xylose via a tin
complex of L-arabinose.
Imbach et al. have described the synthesis of thioriboses protected by
benzyl groups8,9 and more recently have described a synthesis of 1-O-acetyl-
2,3,5-tri-O-benzoyl-4 thioribofuranose from L-lyxose, in 14% overall yield.7
We now report our work in which we have synthesised a variety of
4-thiofuranoses with ester protection. We also report the synthesis of a
D-thioribose starting from a readily available D-thioribose and avoiding
the use of expensive L-lyxose derivatives.
Thus the L-thioarabinose 3 and L-thiolyxose 10 were made from the
D-xylose 1 and the D-ribose 8 derivatives respectively, while the D-thioxylose
6 and D-thioribose 13 were made from the L-arabinose 4 and L-lyxose 11.
In addition a facile inversion at the C-4 position provided a means of con-
verting the D-ribose dithioacetal 9 to the L-lyxose dithioacetal 12, thus avoid-
ing the use of the very expensive L-lyxose 11 starting material for the
synthesis of D-thioribose 13. Surprisingly an attempt to convert the
D-xylose-dithioacetal 2 to the L-arabinose dithioacetal 5, under the same
conditions failed.
DISCUSSION
The initial step in the synthesis involved conversion of the appro-
priate tribenzoyl substituted furanoside 1, 4, 8 or 11 to the open chain
dibenzyl dithioacetal 2, 5, 9 or 12 using benzyl mercaptan in the pre-
sence of a catalytic amount of titanium tetrachloride.5 While some ester
migration was observed in this reaction, under the conditions employed
the required dibenzyl dithioacetals constituted the major products. In
the case of 5, a minor side-product was isolated and tentatively identi-
fied from its 1H NMR spectrum as 1-thiobenzyl-2,3,5-tri-O-benzoyl-L-
arabinose the expected intermediate in this reaction. The crystallised
materials thus obtained appeared to be quite stable, whereas alcoholic
solutions showed evidence of further migration. The crude dithioacetals
were purified by chromatography on silica, and with the exception of
12 appeared reasonably stable to this procedure. The exception 12 under-
went considerable migration and could only be obtained in 26% yield as
a result.
Conversion of the dibenzyl dithioacetals to thiofuranose sugars was
achieved either by mesylation of the 4-hydroxyl followed by cyclisation, or

ORDER
REPRINTS
THIOFURANOSE SUGARS
3831
directly by treatment with triflic anhydride in pyridine. Cyclisation of the
mesylate was carried out either by heating a solution of the mesylate in
butan-2-one in the presence of sodium iodide and triethylamine, as in the
case of 7, or simply by heating in xylene as in the case of 14. The more direct
treatment with triflic anhydride was found when an unsuccessful attempt
was made to invert the C-4 hydroxyl using the method of Coe et al.,10 and
with the exception of the L-arabinose dithioacetal 5, gave better overall
Reagents: (i) BnSH, TiCl4, toluene, (ii) trifluoromethanesulphonic anhydride, pyri-
dine, (iii) methanesulphonyl chloride, pyridine, chloroform, (iv) NaI, Et3N, 2-buta-
none, or alternatively reflux in xylene, (v) formic acid, PPh3, DEAD, toluene, then
MeOH, Amberlyst.

ORDER
REPRINTS
3832
BIRTWISTLE ET AL.
yields. The exception 5 gave the D-thioxylose 6 in 15% crude yield, however
no attempt was made to optimise this reaction, which may be capable of
improvement. The b-anomer was the major product in each case, and in the
case of L-thioarabinose 3 was formed almost exclusively.
Attempts to invert the C-4 position and simultaneously introduce a
mesyl or tosyl group using the appropriate zinc sulphonate11 under
Mitsunobu conditions proved futile in our hands, as did various other
means of effecting this inversion.
However, the introduction of a formate ester, using formic acid, tri-
phenylphosphine and DEAD,12 followed by its methanolysis in the presence
of the acidic resin Amberlyst-15, provided a means of converting 9 to 12.
The reasons for the failure of 2 to undergo a similar inversion to 5 are not
clear. While a variety of ester functions could be introduced in this way,
attempts to remove them resulted in scrambling to give a mixture of iso-
meric dithioacetals having a hydroxyl in the 2,3 or 4-position, even under
such mild conditions as aqueous bicarbonate. Formate proved capable of
removal with only limited scrambling.
EXPERIMENTAL
IR spectra were recorded using a Perkin-Elmer 1605 FT spectrometer.
1H NMR spectra were recorded in CDCl3 in a Bruker AC300 instru-
ment (300 MHz) with tetramethylsilane as internal standard (J values are
given in Hz).
Mass spectra were recorded on a Finnigan MAT 4500 instrument.
M.p.s. were recorded with a Buchi m.p. apparatus and were
uncorrected.
Solvents were dried over MgSO4 and were evaporated under reduced
pressure using a rotary evaporator.
Thin-layer-chromatography was carried out on silica gel plates using
toluene-ethyl acetate, 10 : 1, as eluent.
Column chromatography was carried out on silica (70–230 mesh).
2,3,5-Tri-O-benzoyl-D-xylose Dibenzyl Dithioacetal 2
A mixture of 1-O-acetyl-2,3-5-tri-O-benzoyl-D-xylofuranose 1 (10.1 g,
0.02 mole), benzyl mercaptan (23.6 mL, 0.2 mole) and anhydrous toluene
(10 mL) was stirred while cooling in an ice-bath. Titanium tetrachloride
(1.1 mL, 0.01 mole) was added, giving a red solution. After 10 min the ice-
bath was removed and the mixture was stirred at room temperature for 2 h.

ORDER
REPRINTS
THIOFURANOSE SUGARS
3833
The solution was then poured into sat. sodium bicarbonate solution
(200 mL) and the product extracted into ether (3 ꢀ 100 mL). The extracts
were washed with sat. sodium bicarbonate solution (2 ꢀ 100 mL) then with
sat. brine (100 mL) and dried. Removal of the ether left a colourless oil
(36.7 g). Column chromatography on silica (500 g), using toluene–ethyl acet-
ate (10 : 1) as eluent afforded 2,3,5-tri-O-benzoyl-D-xylose dibenzyl dithioace-
tal 2 as a colourless gum (13.26 g, 96%) which crystallised over several
weeks. Recrystallisation of part (5.0 g) of this solid from methanol
(40 mL) gave a white crystalline solid (2.8 g); mp 109–111ꢁC (found: C,
69.01; H, 5.24; S. 9.73. C40H36O7S2 requires C, 69.34; H, 5.24; S, 9.26%);
d
n max (Nujol)/cmꢂ1 3532 (OH), 1728 (CO) and 1718 (CO); H 7.90–7.56
(6H, 3d, 3 oBz), 7.50–6.75 (19H, m, 2Bn and 3m,p Bz) 6.40 (1H, dd, J 3 and 8,
H2), 5.67 (1H, dd, J 2 and 8. H3), 4.09 (1H, dd, J 6 and 12, H5), 4.03 (1H,
dd J 4 and 12, H50), 3.81 (1H, d, J 14, 1=2 SCH2), 3.70 (1H, d, J 3, 1H), 3.68
(1H, d, J 5, 1=2 SCH2), 3.63 (1H, d, J 5, 1=2 SCH2), 3.56 (1H, d, J 14,
1=2 SCH2), 3.07 (1H, m, H4).
2,3,5-Tri-O-benzoyl-L-arabinose Dibenzyl Dithioacetal 5
A
mixture of 1-O-methyl-2,3,5-tri-O-benzoyl-L-arabinofuranose
(20.0 g, 0.042 mole) and benzylmercaptan (50 mL, 0.42 mole) was treated
with titanium tetrachloride (2.2 mL, 0.02 mole) as for 2 above. Work-up
after 4 h followed by chromatography gave the minor component, 1-thio-
d
benzoyl-2,3,5-tri-O-benzyl-L-arabinose, as a gum (0.97 g, 4%); H 8.01 (2H,
o
o
o
d, Bz), 7.95 (2H, d, Bz), 7.88 (2H, d, Bz), 7.50–7.02 (14H, m, Bn and
m,pBz), 5.52 (1H, d, J 4, H3), 5.46 and 5.38 (2H, 2S, H1 and H2), 4.67 (3H, m,
H4 and H5), 3.38 (1H, d, J 13, 1=2 SCH2), 3.27 (1H, d, J 13 1=2 SCH2).
The major component 2,3,5-tri-O-benzoyl-L-arabinose dibenzyl dithio-
acetal 5, was obtained as a brittle foam (15.77 g, 54%); (Found: C, 68.43; H,
5.20; S, 9.98. C40H36O7S2 requires C, 69.43; H, 5.24; S, 9.26%); n max
(melt)/cmꢂ1 3498 (OH), 1724 (CO); dH 7.97 (2H, d, oBz), 7.92 (2H, d,
o
oBz), 7.86 (2H, d, Bz), 7.52–6.96 (19H, m, Bn and m,pBz), 5.74 (2H, m,
H2 and H3), 4.34 (1H, dd, J 3 and 12, H5), 4.17 (1H, dd, J 6 and 12, H50),
3.81 (2H, m, H1 and H4), 3.74 (2H, s, SCH2), 3.69 (2H, s, SCH2).
2,3,5-Tri-O-benzoyl-D-ribose Dibenzyl Dithioacetal 9
A
(9.68 g, 0.0192 mole) and benzylmercaptan (22.7 mL, 0.192 mole) was trea-
mixture of 1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranose
8
ted with titanium tetrachloride (1.1 mL, 0.01 mole) as for 5 above. Work-up

ORDER
REPRINTS
3834
BIRTWISTLE ET AL.
after 2 h followed by chromatography gave 2,3,5-tri-O-benzoyl-D-ribose
dibenzyl dithioacetal 9 as a colourless gum (12.57 g, 94%), which crystallised
over several weeks. Recrystallisation from methanol gave colourless crys-
tals, m.p. 92–93ꢁC; (Found: C, 69.26; H, 5.19; S, 9.82. C40H36O7S2 requires
C, 69.34; H, 5.24; S, 9.26%); n max (Nujol)/cmꢂ1 3510 (OH), 1725 (CO) and
d
1705 (CO); H 8.08 (2H, d, oBz), 8.01 (2H, d, oBz), 7.78 (2H, d, oBz),
7.62–6.88 (19H, m, Bn and m,pBz), 5.98 (1H, dd, J 5 and 6, H2), 5.82 (1H,
dd, J 5 and 6, 3H), 4.50 (1H, dd, J 4 and 12, H5), 4.33 (1H, dd, J 6 and 12,
H50), 4.22 (1H, ddd, J 4, 5 and 6, H4), 4.01 (1H, d, J 5, H1), 3.92 (1H, d, J
14, 1=2 SCH2), 3.77 (1H, d, J 14, 1=2 SCH2) 3.74 (2H, ABq, SCH2).
2,3,5-Tri-O-benzoyl-L-lyxose Dibenzyl Dithioacetal 12
A mixture of 2,3,5-tri-O-benzoyl-D-ribose dibenzyl dithioacetal 9
(1.39 g, 0.002 mole), formic acid (0.15 mL, 0.004 mole) triphenylphosphine
(1.04 g, 0.004 mole) and anhydrous toluene (40 mL) was stirred under nitro-
gen. Diethyl azodicarboxylate (0.32 mL, 0.002 mole) was added and stirring
continued for 6 h. A second portion of diethyl azodicarboxylate (0.32 mL,
0.002 mole) was added and stirring continued overnight (approx. 18 h). The
reaction mixture was poured into a mixture of water (150 mL) and sat.
ammonium chloride solution (10 mL). The product was extracted into
ether (3 ꢀ 100 mL) and the extracts washed with sat. brine (100 mL) then
dried. Removal of the solvent left a pale yellow semi-solid (3.64 g).
Triphenylphosphine oxide was removed by column chromatography on
silica (100 g), using toluene–ethyl acetate (15 : 1) as eluent. The crude
2,3,5-tri-O-benzoyl-4-formyl-L-lyxose dibenzyl dithioacetal thus obtained, as
a colourless gum (1.52 g), was dissolved in methanol (120 mL) and the
solution stirred over Amberlyst-15 (5.0 g), at room temperature, for 22 h.
The Amberlyst was filtered off, methanol removed, and the residue taken up
in ether (150 mL) which was washed with water (100 mL), sat. brine
(100 mL), dried and evaporated to yield 2,3,5-tri-O-benzoyl-L-lyxose dibenzyl
dithioacetal 12 as a white foam (1.1 g, 79%). Crystallisation from methanol
(20 mL) gave a white crystalline solid (0.53 g, 38%) m.p. 118–119ꢁC.
(Found: C, 69.88; H, 5.46; S, 9.37. C40H36O7S2 requires C, 69.34; H, 5.24;
S, 9.26%); n max (Nujol)/cmꢂ1 3500 (OH), 1735 (CO), 1725 (CO); 1700
d
o
o
o
(CO); H 8.12 (2H, d, Bz), 7.91 (2H, d, Bz), 7.82 (2H, d, Bz), 7.14–6.82
(19H, m, Bn and m,pBz), 6.02 (1H, dd, J 2 and 9, H2), 5.73 (1H, dd, J 1 and
9, H3), 4.34 (1H, dd, J 6 and 12, H5), 4.27 (1H, dd, J 7 and 12, H50), 4.12
(1H, ddd, J 1, 6 and 7, H4), 3.83 (1H, d, J 14, 1=2 SCH2), 3.76 (1H, d, J 2,
H1), 3.68 (1H, d, J 14, 1=2 SCH2), 3.66 (2H, ABq, SCH2).

ORDER
REPRINTS
THIOFURANOSE SUGARS
3835
2,3,5-Tri-O-benzoyl-L-lyxose Dibenzyl Dithioacetal 12
mixture of 1-O-methyl-2,3,5-tri-O-benzoyl-L-lyxofuranose 11
A
(4.76 g, 0.01 mole) and benzylmercaptan (11.8 mL, 0.10 mole) was treated
with titanium tetrachloride (0.55 mL, 0.005 mole) as for 5 above. Work-up
after 2.5 h followed by chromatography gave 2,3,5-tri-O-benzoyl-L-lyxose
dibenzyl dithioacetal 12 as a colourless glass (1.8 g, 26%). Crystallisation
from methanol gave a white solid, m.p. 119–120ꢁC. (Found: C, 69.17; H,
1
5.27. C40H36O7S2 requires C, 69.34; H, 5.24%), the H NMR spectrum of
which was identical to that of 12 made via the inversion described above.
1-Thiobenzyl-2,3,5-O-tribenzoyl-4-thio-b-L-arabinofuranose 3
A solution of 2,3,5-tri-O-benzoyl-D-xylose dibenzyl dithioacetal 2
(3.46 g, 0.005 mole) in anhydrous pyridine (40 mL) was stirred while cooling
in an ice-bath. Trifluoromethanesulphonic anhydride (1.7 mL, 0.010 mole)
was added and the resulting solution was then warmed to room temperature
and stirred for 2 h. The solution was poured into water (250 mL) and the
product extracted into ethyl acetate (3 ꢀ 100 mL). The extracts were washed
with 1 N hydrochloric acid (3 ꢀ 100 mL), sat. sodium bicarbonate solution
(3 ꢀ 100 mL), sat. brine (100 mL) then dried. The extracts were concen-
trated, filtered through silica (100 g) and the solvent removed to give a
pale orange semi-solid (2.49 g, 85%). Crystallisation from ethanol (30 mL)
gave 1-thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-ꢀ-L-arabinofuranose 3 as a white
crystalline solid (1.83 g, 63%) m.p. 96–97ꢁC. (Found: C, 67.57; H, 4.77.
d
o
C33H28O6S2 requires C, 67.78; H, 4.82%); H 8.09 (2H, d, Bz), 8.01 (2H,
d, oBz), 7.96 (2H, d, oBz), 7.65–6.91 (14H, m, Bn and m,pBz), 6.17 (1H, dd, J
5 and 6, H3), 5.81 (1H, dd, J 5 and 6, 2H), 4.73 (2H, m, H5 and H1), 4.62
(1H, dd, J 7 and 11, 5H0), 3.87 (3H, m, H4 and SCH2).
4-O-Methanesulphonyl-2,3-5-tri-O-benzoyl-L-arabinose
Dibenzyl Dithioacetal 7
2,3,5-Tri-O-benzoyl-L-arabinose dibenzyl dithioacetal
5 (11.31 g,
0.0163 mole) and pyridine (5 mL) were dissolved in alcohol-free chloroform
(70 mL). The solution was cooled to 0ꢁC, methanesulphonyl chloride
(1.87 mL, 0.0242 mole) added, and the reaction mixture was stirred at
room temperature for 18 h. Chromatography of the reaction mixture on
silica using toluene–ethyl acetate (11 : 1) as eluent gave 4-O-methanesulpho-
nyl-2,3,5-tri-O-benzoyl-L-arabinose dibenzyl dithioacetal 7 as a sticky white

ORDER
REPRINTS
3836
BIRTWISTLE ET AL.
solid (9.15 g, 73%), which appeared to be unstable and was stored below
5ꢁC. (Found: C, 63.59; H, 4.97; S, 13.19. C41H38O9S3 requires C, 63.87; H,
d
o
o
o
4.97; S, 12.48%); H 7.99 (2H, d, Bz), 7.94 (2H, d, Bz), 7.87 (2H, d, Bz),
7.52–6.98 (19H, m, Bn and m,pBz), 6.06 (1H, t, J 5, H3), 5.65 (1H, dd, J 5
and 5, H2), 5.11 (1H, td, J 5 and 8, H4), 4.47 (1H, dd, J 5 and 13, H5), 4.32
(1H, dd, J 8 and 13, H50), 3.80 (1H, d, J 6, H1), 3.76 (2H, s, SCH2), 3.74
(2H, ABq, SCH2), 2.89 (3H, s, Ms).
1-Thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-D-xylofuranose 6
A
mixture of 4-O-methanesulphonyl-2,3,5-tri-O-benzoyl-L-arabi-
nose dibenzyl dithioacetal 7 (20.1 g, 0.026 mole), triethylamine (7.2 mL,
0.052 mole) and sodium iodide (38.9 g, 0.26 mole) was stirred at reflux, in
methyl ethyl ketone (250 mL), for 30 h. The reaction mixture was cooled
then washed with water (100 mL), 2 N hydrochloric acid (100 mL), sat.
sodium bicarbonate (100 mL), brine (100 mL) and dried. Removal of the
solvent followed by chromatography on silica using toluene as eluent, gave a
mixture of a and b anomers of 1-thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-D-
xylofuranose 6, as an orange gum (5.51 g, 36%). (Found: C, 67.95; H,
4.97; S, 11.47. C33H28O6S2 requires C, 67.78; H, 4.82; S, 10.97%); dH
o
o
o
b-anomer, 8.01 (2H, d, Bz), 7.95 (2H, d, Bz), 7.86 (2H, d, Bz), 7.55–
7.08 (14H, m, Bn and m,pBz), 5.92 (1H, t, J 5, H3), 5.78 (1H, dd, J 4 and
5, H2), 4.64 (1H, dd, J 7 and 12, H5), 4.51 (1H, dd, J 6 and 12, H50), 4.36
(1H, d, J 4, H1), 4.23 (1H, m, H4), 3.86 (2H, ABq, SCH2); a-anomer,
8.07–7.80 (6H, 3d, 3oBz), 7.57–7.08 (14H, m, Bn and m,pBz), 5.96 (1H, t, J
5, H3), 5.78 (1H, t, J 5, H2), 4.68 (1H, d, J 5, H1), 4.51 (1H, dd, J 7 and 11,
H50), 4.40 (1H, dd, J 11 and 6, H50), 4.28 (1H, m, H4), 3.78 (2H, s, SCH2).
1-Thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-L-lyxofuranose 10
A solution of 2,3,5-tri-O-benzoyl-D-ribose dibenzyl dithioacetal 9
(14.10 g, 0.0204 mole) in anhydrous pyridine (30 mL) was treated with tri-
fluoromethanesulphonic anhydride (6.0 mL, 0.0357 mole) as for 3 above.
Work-up followed by chromatography gave 1-thiobenzyl-2,3,5-tri-O-ben-
zoyl-4-thio-L-lyxofuranose 10 as a pale yellow gum (11.2 g, 94%), with the
b anomer 10a and the a anomer 10b in the ratio of approx. 3:1. TLC showed
two contiguous spots. (Found: C, 68.47; H, 5.43. C33H28O6S2 requires C,
d
67.78; H, 4.82%); H, b-anomer, 8.02–7.80 (6H, 3d, 3oBz), 7.55–7.08 (14H,
m, Bn and m,pBz), 6.19 (1H, dd, J 4 and 6, H3), 5.77 (1H, dd, J 4 and 6, 2H),
4.69 (1H, dd, J 7 and 11, H5), 4.63 (1H, d, J 6, H1), 4.59 (1H, dd, J 7 and 11,

ORDER
REPRINTS
THIOFURANOSE SUGARS
3837
H50), 4.32 (1H, dt, J 6 and 7, H4), 3.99 (2H, ABq, SCH2); a-anomer
8.02–7.80 (6H, 3d, 3oBz), 7.55–7.08 (14H, m, Bn and m,pBz), 6.06 (1H, dd,
J 4 and 6, H3), 5.80 (1H, dd, J 4 and 6, H2), 4.74 (1H, dd, J 7 and 11, H5),
4.73 (1H, d, J 6, H1), 4.63 (1H, dd, J 7 and 11, H50), 4.15 (1H, dt, J 6 and 7,
H4), 3.83 (2H, ABq, SCH2); m/z (C1, NH3), 602 (M þ NH4)þ.
4-O-Methanesulphonyl-2,3,5-tri-O-benzoyl-L-lyxose Dibenzyl
Dithioacetal 14
2,3,5-Tri-O-benzoyl-L-lyxose dibenzyl dithioacetal 12 (0.3 g,
0.43 m mole) and pyridine (2 mL) were dissolved in alcohol-free chloroform
(10 mL). The solution was cooled to 0ꢁC, methanesulphonyl chloride
(0.05 mL, 0.65 m mole) added, and the reaction mixture was stirred at room
temperature for 3 h. Chromatography of the reaction mixture on silica using
toluene–ethyl acetate (9 : 1) as eluent gave 4-O-methanesulphonyl-2,3,5-tri-O-
benzoyl-L-lyxose dibenzyl dithioacetal 14 as a colourless gum (0.3 g, 90%)
which crystallised on standing, m.p. 55–58ꢁC. (Found: C, 63.40; H, 4.95.
C41H38O9S3 requires C, 63.87; H, 4.97%); dH 8.11 (2H, d, oBz), 7.99 (2H, d,
o
oBz), 7.78 (2H, d, Bz), 7.65–6.85 (19H, m, Bn and m,pBz), 5.99 (2H, m, H2
and H3), 5.77 (1H, dt, J 5 and 8, H4), 4.60 (1H, dd, J 5 and 13, H5), 4.43
(1H, dd, J 8 and 13, H50), 3.90 (1H, d, J 14, 1=2 SCH2), 3.82 (1H, d, J 3, H1),
3.73 (1H, d, J 14, 1=2 SCH2), 3.70 (2H, s, SCH2), 3.11 (3H, s, Ms).
1-Thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-D-ribofuranose 13
A
solution of 4-O-methanesulphonyl-2,3,5-tri-O-benzoyl-L-lyxose
dibenzyl dithioacetal 14 (100 mg, 0.13 m mole) in xylene (1 mL) was heated
at reflux for 1 h. Chromatography on silica using n-hexane–ethyl acetate
(95 : 5) as eluent afforded 1-thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-ꢀ-D-ribo-
furanose 13a as a gum (30 mg, 39%), which was homogeneous on t.l.c.;
o
o
o
dH 8.03 ((2H, d, Bz), 8.02 (2H, d, Bz), 7.90 (2H, d, Bz), 7.55–7.20 (14H,
m, Bn and m,pBz), 6.07 (1H, dd, J 3 and 7, H3), 5.94 (1H, t, J 3, H2), 4.72
(1H, dd, J 7 and 12, H5), 4.55 (1H, dd J 7 and 12, H50), 4.44 (1H, d, J 3, H1),
4.18 (1H, q, J 7, H4), 4.00 (2H, ABq, SCH2); m/z (C1, NH3), 602 (M þ NH4)þ.
The second component, 1-thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-ꢁ-D-
ribofuranose 13b was obtained as a gum (10 mg, 13%), which was homo-
d
o
o
o
geneous on t.l.c. H 8.07 (2H, d, Bz), 7.99 (2H, d, Bz), 7.97 (2H, d, Bz),
7.60–7.25 (14H, m, Bn and m,pBz), 5.95 (1H, t, J 4, H2), 5.68 (1H, dd, J 4
and 6 H3), 4.75 (1H, d, J 4, H1), 4.62 (1H, dd, J 6 and 12, H5), 4.55 (1H, dd,

ORDER
REPRINTS
3838
BIRTWISTLE ET AL.
J 6 and 12, H50), 4.31 (1H, q, J 6, H4), 3.86 (2H, Abq, SHC2); m/z (C1,
NH3), 602 (M þ HN4)þ.
1-Thiobenzyl-2,3,5-tri-O-benzoyl-4-thio-b-D-ribofuranose 13a
2,3,5-O-Tribenzoyl-L-lyxosedibenzyldithioacetal12(0.69 g,1.0 m mole)
was treated with trifluoromethanesulphonic anhydride as for 3 above.
Extraction into ether followed by chromatography on silica afforded 1-thio-
benzyl-2,3,5-tri-O-benzoyl-4-thio-b-D-ribofuranose 13a as a colourless glass
1
(0.3 g, 51%), the H NMR spectrum of which was identical to that of 13a
made by cyclization of compound 14.
REFERENCES
1. Bobek, M.; Whistler, R. Methods Carbohydrate Chem. 1972, 6, 292.
2. Reist, E.; Fisher, L.; Goodman, L. J. Org. Chem. 1968, 33, 189.
3. (i)Dyson, M.R.;Coe, P.L.;Walker,R.T. Carbohydr.Res. 1991, 216,237.
(ii) Dyson, M.R.; Coe, P.L.; Walker, R.T. J. Med. Chem. 1991, 216, 237.
4. Bredenkamp, M.W.; Holzapfel, C.W.; Swanepoel, A.D. Tetrahedron
Lett. 1990, 31, 2759.
5. Bredenkamp, M.W.; Holzapfel, C.W.; Swanepoel, A.D. S. Afr. J.
Chem. 1991, 44(1), 31.
6. Kumar, V.; Dev, S. Tetrahedron Lett. 1983, 24, 1289.
7. Leydier, C.; Bellon, L.; Barascut, J.-L.; Imbach, J.-L. Nucleosides and
Nucleotides 1995, 14(3–5), 1027.
8. Bellon, L.; Barascut, J.-L.; Imbach, J.-L. Nucleosides and Nucleotides
1992, 11(8), 1467.
9. Bellon, L.; Leydier, C.; Barascut, J.-L.; Imbach, J.-L. Nucleosides and
Nucleotides 1993, 12(8), 847.
10. Coe, D.M.; Hilpert, H.; Noble, S.A.; Peel, M.R.; Roberts, S.M.;
Storer, R. J. Chem. Soc., Chem. Commun. 1991, 312.
11. Galynker, I.; Still, W.C. Tetrahedron Lett. 1982, 23, 4461.
12. Mitsunobu, O.; Eguchi, M. Bull. Chem. Soc. Jpn. 1971, 44, 3427.
Received in the UK November 20, 2000

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request
Permission/Reprints Here" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
(AAP) website for guidelines on Fair Use in the Classroom.
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our Website
User Agreement for more details.
Order now!
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC100108233