An improved synthesis of 5-thio-D-ribose from D-ribono-1,4-lactone.

Article abstract of DOI:10.1016/S0008-6215(02)00170-2

5-Thio-D-ribopyranose was synthesized from D-ribono-1,4-lactone (1) by two approaches: (i) 5-bromo-5-deoxy-D-ribono-1,4-lactone (2) was successively transformed into 5-bromo-5-deoxy, 5-S-acetyl-5-thio or 5-thiocyanato-D-ribofuranose derivatives; appropriate treatment then lead to 5-thio-D-ribopyranose (7) in 46-48% overall yield and; (ii) 2 was transformed into the 5-S-acetyl-5-thio-D-ribono-1,4-lactone derivative (11). Reduction and deprotection of 11 afforded 5-thio-D-ribopyranose (7) in 57% overall yield.

Full text of DOI:10.1016/S0008-6215(02)00170-2

Carbohydrate Research 337 (2002) 1411–1416
www.elsevier.com/locate/carres
Note
An improved synthesis of 5-thio-
D-ribose from
D-ribono-1,4-lactone
Je´roˆme Lalot, Imane Stasik,* Gilles Demailly, Daniel Beaupe`re
Laboratoire des Glucides, Uni6ersite´ de Picardie Jules Verne, 33 rue Saint-Leu, F-80039 Amiens, France
Received 6 May 2002; received in revised form 14 June 2002; accepted 20 June 2002
Abstract
5-Thio-
D
-ribopyranose was synthesized from
D
-ribono-1,4-lactone (1) by two approaches: (i) 5-bromo-5-deoxy-
-ribofuranose derivatives;
-ribopyranose (7) in 46–48% overall yield and; (ii) 2 was transformed into the
-ribono-1,4-lactone derivative (11). Reduction and deprotection of 11 afforded 5-thio- -ribopyranose (7) in
57% overall yield. © 2002 Elsevier Science Ltd. All rights reserved.
D-ribono-1,4-
lactone (2) was successively transformed into 5-bromo-5-deoxy, 5-S-acetyl-5-thio or 5-thiocyanato-
appropriate treatment then lead to 5-thio-
5-S-acetyl-5-thio-
D
D
D
D
Keywords: 5-Bromo-5-deoxy-
D
-ribono-1,4-lactone; 5-Bromo-5-deoxy-
D-ribofuranose; 5-S-Acetyl-5-thio-D-ribono-1,4-lactone; 5-Thiocyanato-D-ri-
bono-1,4-lactone; 5-Thio-
D-ribopyranose
1. Introduction
into the 5,6-episulfide. The second strategy requires a
primary-O-sulfonate displacement of furanoside by use
of reagents containing nucleophilic sulfur: thiocyanate
ion, benzylthiolate, ethyl xanthate10 and thiolacetic acid
salt,5,8,11 which can be used to give sulfur-containing
products and thence thiosugars by deprotection. Re-
cently, Hughes et al. have used the latter strategy and
5-Thioaldopyranoses1 exhibit remarkable biological
activities, such as inhibition of glycosidases. 5-Thio-
glucose inhibits -glucose transport across membranes
and also the release of insulin.2 5-Thio-
-fucose was
found to be a potent inhibitor of bovine a- -fucosi-
dase.3 Glycosides of 1,5-dithio-
-xylopyranose, in par-
D
-
D
L
L
D
obtained 5-thio-
ribopyranose in 15% overall yield.12 We previously
described a rapid synthesis of 5-bromo-5-deoxy- -pen-
tono-1,4-lactones. Based on our previous results of
synthesis of
-pentonolactams,13 we now report on two
routes for a convenient and efficient synthesis of 5-thio-
-ribopyranose using -ribono-1,4-lactone as starting
material: either via 5-bromo-5-deoxy- -ribose deriva-
tive (Pathway A, Scheme 1) or via the 5-S-acetyl-5-
thio- -ribono-1,4-lactone derivative (Pathway B,
D-ribose from 2,3-O-isopropylidene-D-
ticular, have proved to be orally active antithrombotic
agents.4 Among naturally occurring thiosugars with a
D
sulfur atom in the ring, 5-thio-D-mannose has been
isolated from the marine sponge Clathria pyramida.5
D
Syntheses of thiosugars have been reported since the
1960s.
D
-Ribose,6
D
-galactose,7
L
-rhamnose,8 and 2-
D
D
acetamido-2-deoxy-
D
-glucose9 5-thio-analogs have been
D
synthesized.7 These syntheses require usually tedious
and long synthetic strategies to lead to substantially low
yields. Very often two strategies are employed, which
uses two key steps: conversion of the pyranose structure
into a furanose followed by conversion of a 5,6-epoxide
D
Scheme 1).
2. Results and discussion
In pathway A, selective bromination of the primary
* Corresponding author. Tel.: +33-3-22827566; fax: +33-
3-22827560
hydroxyl group in
bromide in N,N-dimethylformamide gave the 5-bromo-
5-deoxy-
-ribono-1,4-lactone (2)14 (95%), which on iso-
D
-ribono-1,4-lactone (1) by thionyl
E-mail address: imane.stasik@u-picardie.fr (I. Stasik).
1 For a recent review, see Ref. 1.
D
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00170-2

1412
J. Lalot et al. / Carbohydrate Research 337 (2002) 1411–1416
To avoid the necessary generation of the thiol group
from the thioacetate or thiocyanate functionality, we
have attempted the treatment of 4 with sodium sulfide
nonahydrate. However, a mixture of the 1,4-anhydro
compound 14,12 as major product, traces of 8 and
propylidenation gave 3 (80%). More conveniently and
more efficiently, 3 could be obtained by a one pot
sequential bromination-protection of 1 (80%). TLC of
the reduction product of 3 by disiamylborane showed
the presence of a mixture of products. NMR analysis of
the crude mixture shows in particular formation of the
bis-(2,3-O-isopropylidene-D-ribofuranose) 5,5%-sulfide
(15) (Scheme 2) was identified by NMR and mass
spectroscopy. Basic conditions were presumably re-
sponsible of the intramolecular displacement of the
bromide atom by the C-1 oxyanion and formation of
14. In less alcaline conditions, by using sodium sulfide,
the anhydride 14 was undetected but compounds 8 and
15 were obtained in equal amount.
5-deoxy-D-ribono-1,4-lactone derivative due to cleavage
of the CꢀBr bond. On the other hand, when 3 was
treated with diisobutylaluminium hydride (DIBAL-H)
in THF, TLC of the crude product (Table 2) showed
the presence of a single spot. 13C NMR analysis showed
disappearance of the carbonyl group (173.6 ppm) and
the presence of two new signals at 97.7 and 103.5 ppm
characteristic of two anomeric carbons in 4 (95%).
Displacement of the bromide group in 4 with potassium
thioacetate in N,N-dimethylformamide gave 5-S-acetyl-
To prevent any cleavage of the CꢀBr bond during the
reduction step, and to improve the synthesis of 5-thio-
D
-ribopyranose (7), we have investigated a second route
involving reduction of the lactone after displacement of
the bromide group (pathway B, Scheme 1).
2,3-O-isopropylidene-5-thio-
yield. Methanolysis of 5 with sodium methoxide in
MeOH afforded 2,3-O-isopropylidene-5-thio- -ribopy-
ranose (8) (a/b=1:1) in 71% yield. Acid hydrolysis of 8
D
-ribofuranose (5) in 95%
In pathway B, 2 was acetylated to give 9 (90%). A
one pot sequential bromination–acetylation of 1 af-
forded 9 in 90% yield. Displacement of the bromide
group with potassium thiocyanate gave the thiocyanate
10 in 65% yield and treatment of 9 with potassium
thioacetate gave the thioacetate derivative 11 in 95%
isolated yield. When 10 was treated with diisobutylalu-
minium hydride or disiamylborane in THF, TLC
showed the presence of a complex mixture of products.
NMR analysis of the crude material showed that par-
tial deacetylation and reduction of the thiocyanate
group occurred and any trace of expected compound
D
gave 5-thio- -ribopyranose (7) (a/b=1:1) in 90% yield.
D
The 13C NMR spectra showed the presence of a- and
b-forms. In comparison, reaction of 5-bromo-5-deoxy-
2,3-O-isopropylidene- -ribofuranose (4) with potas-
D
sium thiocyanate gave 6 in 98% yield. Treatment of 6
with commercially available zinc in acetic acid10b did
not afford the desired product 7 but required activated
zinc.15 The overall yields of the 1“3“4“5“8“7
reaction sequence and 1“3“4“6“7 were 46 and
48%, respectively.
2,3 - O - isopropylidene - 5 - thiocyanato - D - ribofuranose
Scheme 1. Pathway A: (i) SOBr2/DMF; (ii) acetone/I2; (iii) DIBAL-H/THF; (iv) KSAc/DMF; (v) KSCN/DMF; (vi) activated
zinc/AcOH; (vii) MeONa/MeOH; (viii) TFA/H2O. Pathway B: (i) SOBr2/DMF; (ii) AC2O; (iii) KSCN/DMF; (iv) KSAc/DMF;
(v) disiamylborane/THF; (vi) MeONa/MeOH.

J. Lalot et al. / Carbohydrate Research 337 (2002) 1411–1416
1413

1414
J. Lalot et al. / Carbohydrate Research 337 (2002) 1411–1416
Table 2
13C NMR data
Compound
Chemical shifts (ppm)
Other signals
C-1
C-2
C-3
C-4
C-5
3 a
4a a
4b a
5a a
173.3
97.7
103.5
96.9
77.7
75.1
83.3
83.3
80.6
80.5
87.1
83.1
33.0
33.6
33.6
31.1
113.5(CMe2)
26.4; 25.2 (CMe2)
115.0 (CMe2)
26.5; 25.3 (CMe2)
113.2(CMe2)
26.8; 25.3 (CMe2)
115.0 (CMe2)
79.8
86.1
79.9–79.7
26.5; 25.3 (CMe2)
SCOCH3: 195.9; SCOCH3: 30.9
112.9 (CMe2)
5b a
103.5
83.9
86.4
86.4
33.7
26.5; 25.3 (CMe2)
SCOCH3: 195.9; SCOCH3: 30.9
112.3 (SCN, CMe2)
26.3; 24.9 (CMe2)
111.4 (SCN, CMe2)
26.3; 24.9 (CMe2)
6a a
6b a
96.4
82.8–80.0–79.69
86.0–86.0–83.6
35.9
37.6
103.2
7a b,c
7b b,c
8a a,d
73.9
73.0
75.1
74.1
74.5
72.1
71.6
71.3
69.5
70.6
70.2
66.0
28.5
22.7
26.8
112.4 (CMe2)
25.6; 25.2 (CMe2)
109.3 (CMe2)
26.6; 25.2 (CMe2)
20.7; 20.4 (COCH3)
170.1; 169.6 (COCH3)
111.4 (SCN); 20.8; 20.5 (COCH3)
170.9; 169.7 (COCH3)
194.5 (SCOCH3); 30.2 (SCOCH3)
168.9; 169.9 (OCOCH3); 20.4; 20.1 (OCOCH3)
195.3 (SCOCH3); 30.9 (SCOCH3)
170.3; 170.3 (OCOCH3); 20.9; 20.9 (OCOCH3)
195.9 (SCOCH3); 309 (SCOCH3)
170.3; 170.3 (OCOCH3); 20.9; 20.9 (OCOCH3)
8b a,d
9 a
79.6
170.5
170.1
170.8
95.6
76.2
66.6
66.5
66.2
79.6
79.5
73.1
70.4
70.1
70.3
72.4
76.1
67.2
81.8
81.1
81.0
71.3
73.8
27.5
30.8
34.8
29.7
31.5
33.2
10 a
11 a
13a a
13b a
100.4
a In CDCl3.
b In D2O.
c Refs. 6,12.
d Ref. 12.
Scheme 2.
(12) was formed. On another hand, reduction of 11
with disiamylborane in THF gave 13 in 75% yield.
3. Experimental
Methanolysis of 13 gave 5-thio-
b=1:1) in 89% yield. The overall yield of the 1“9“
11“13“7 reaction sequence was 57%.
D
-ribopyranose 7 (a/
General methods.—Melting points were determined
on a Buchi 535 apparatus and are uncorrected. Optical
rotations were measured with a JASCO DIP-370 digital

J. Lalot et al. / Carbohydrate Research 337 (2002) 1411–1416
1415
polarimeter, using a sodium lamp (u=589 nm) at
pressure. The crude material was partitioned between
CH2Cl2 and water. The CH2Cl2 extracts were dried
filtered and concentrated. The residue was chro-
matographed on silica gel. Elution with 4:1 hexanes–
EtOAc gave 5 (0.47 g, 95%) as a colorless syrup: Rf 0.51
(7:3 hexanes–EtOAc); [h]D −7° (a/b=3:7) (c 1.04,
CH2Cl2). Anal. Calcd for C10H16O5S: C, 48.37; H, 6.50.
Found: C, 48.03; H, 6.69.
1
20 °C. H and 13C NMR spectra (Tables 1 and 2) were
recorded in D2O or CDCl3. Me4Si was used as an
internal standard on a Bruker 300 MHz spectrometer.
Thin-layer chromatography (TLC) was performed on
E. Merck glass plates silica gel sheets (Silica Gel F254
)
and visualized under UV light and stained with phos-
phomolybdic acid–aq H2SO4 solution. Column chro-
matography was performed on Kiesel gel (E. Merck
230–400 mesh). All solvents were distilled before use.
2,3-O-Isopropylidene-5-thiocyanato-D-ribonofuranose
(6).—To a solution of the lactone (4) (0.5 g, 2 mmol) in
anhyd DMF (5 mL), under an inert atmosphere, was
added potassium thiocyanate (0.38 g, 2 equiv). The
mixture was kept overnight under an inert atmosphere
at 70 °C. The solution was concentrated and the crude
material was partitioned between CH2Cl2 and water.
The CH2Cl2 extracts were dried filtered and concen-
trated. The residue was chromatographed on silica gel.
Elution with 7:3 hexanes–EtOAc gave 6 (0.45 g, 98%)
as a white solid: Rf 0.57 (3:2 hexanes–EtOAc); mp
67.8–68.8 °C, [h]D −8° (a/b=1:4). Anal. Calcd for
C9H13NO4S: C, 46.74; H, 5.67; N, 6.06. Found: C,
46.78; H, 5.41; N, 5.93.
5-Bromo-5-deoxy-2,3-O-isopropylidene-D-ribono-1,4-
lactone (3).— -Ribono-1,4-lactone (1) (0.5 g, 3.4
D
mmol) was stirred in anhyd DMF (5 mL) under an
inert atmosphere. Freshly distilled SOBr2 (0.445, 1.7
equiv) was added dropwise at 0 °C. The mixture was
stirred for 30 min, then MeOH was added and the
solution was kept for 10 min at rt and concentrated.
The crude material was diluted with water and washed
with CH2Cl2. The water extracts were, filtered and
concentrated. The residue was treated with anhyd ace-
tone (20 mL) and I2 (150 mg, 0.59 mmol). The reaction
mixture was stirred overnight at rt under an inert
atmosphere. Saturated aq sodium thiosulfate was added
to the mixture. The solution was concentrated under
diminished pressure to yield a crude product which was
partitioned between CH2Cl2 and water. The CH2Cl2
extracts were dried, filtered and concentrated under
reduced pressure. The residue was chromatographed on
silica gel. Elution with (4:1 then 3:2) hexanes–EtOAc
gave 3 (0.68 g, 80%) as white solid: Rf 0.89 (1:1
hexanes–EtOAc); mp 82–84 °C; [h]D −45° (c 0.59,
CHCl3). Anal. Calcd for C8H11BrO4: C, 38.27; H, 4.42;
Br, 31.82. Found C, 38.07; H, 4.12; Br 31.94.
2,3-O-Isopropylidene-5-thio- -ribopyranose (8).—To
D
a solution of the S-acetyl derivative 5 (0.5 g, 1.4 mmol)
in MeOH (5 mL) was added NaOMe (0.21 g, 4 mmol).
The mixture was stirred for 30 min at rt. The solution
was passed through ion exchange resin (Dowex 50×8-
100 ion) filtered and concentrated. The residue was
chromatographed on silica gel. Elution with 1:1 hex-
anes–EtOAc gave 8 (0.29 g, 71%) as a colorless syrup:
Rf 0.42 (1:1 hexanes–EtOAc), lit.: for the b form: mp
136–138 °C, [h]D −37° (−30° final) (c 1.44, MeOH).12
Anal. Calcd for C8H14O4S: C, 46.58; H, 6.84; Found: C,
46.63; H, 6.92.
5-Bromo-5-deoxy-2,3-O-isopropylidene-D-ribofura-
nose (4).—To a solution of 3 (1 g, 3.4 mmol) in dry
toluene or freshly distilled THF (10 mL), under an inert
atmosphere, at −80 °C was added DIBAL-H (3.4 mL,
1.1 equiv). The mixture was stirred for 30 min at
−80 °C, then MeOH was added and the solution was
kept for 30 min at rt and concentrated under reduced
pressure. The crude material was partitioned between
CH2Cl2 and water. The CH2Cl2 extracts were dried
filtered and concentrated. The residue was chro-
matographed on silica gel. Elution with 7:3 hexanes–
EtOAc gave 4 (0.96 g, 95%) as a white solid: Rf 0.89
(1:1 hexanes–EtOAc); mp 73.5–74.5 °C; [h]D −39°
(a/b=1:9) (c 1.04, CH2Cl2). Anal. Calcd for
C8H13BrO4: C, 37.96; H, 5.18; Br, 31.57. Found: C,
37.93; H, 5.22; Br, 31.61.
2,3-Di-O-acetyl-5-bromo-5-deoxy-
D-ribono-1,4-lac-
tone (9).— -Ribono-1,4-lactone (1) (0.5 g, 3.4 mmol)
D
was stirred in anhyd DMF (5 mL) under an inert
atmosphere. Freshly distilled SOBr2 (0.445 mL, 1.7
equiv) was added dropwise at 0 °C. The mixture was
stirred at rt for 30 min, then MeOH was added and the
solution was kept for 10 min at rt and concentrated.
The crude material was treated with Ac2O (10 mL).
After 15 min at 60 °C under an inert atmosphere, the
solution was concentrated and the residue was added to
water and extracted with CH2Cl2; the extracts were
dried, filtered and concentrated under reduced pressure.
The residue was chromatographed on silica gel. Elution
with 4:1, then 3:2 hexanes–EtOAc gave 9 (0.90 g, 90%)
as a colorless syrup: Rf 0.60 (3:2 hexanes–EtOAc); [h]D
+3° (c 3.62, CH2Cl2). Anal. Calcd for C9H11BrO6: C,
36.63; H, 3.76; Br, 27.08. Found: C, 37.02; H, 4.13; Br,
27.82.
5-S-Acetyl-2,3-O-isopropylidene-5-thio-D-ribofura-
nose (5).—To a solution of 5-bromo-5-deoxy-2,3-O-
isopropylidene- -ribofuranose (4) (0.5 g, 2 mmol) in
D
anhyd DMF (5 mL) was added potassium thioacetate
(0.27 g, 2.4 mmol). The mixture was kept for 10 min,
under an inert atmosphere, at rt. The suspension was
filtered, and the filtrate was concentrated under reduced
2,3-Di-O-acetyl-5-thiocyanato-D-ribono-1,4-lactone
(10).—To a solution of 3 (0.5 g, 1.7 mmol) in anhyd
DMF (5 mL) was added potassium thiocyanate (0.23 g,
3.4 mmol). The mixture was stirred under an inert

1416
J. Lalot et al. / Carbohydrate Research 337 (2002) 1411–1416
atmosphere at 70 °C for 10 min. The mixture was
concentrated under reduced pressure and the residue
was added to water and extracted with CH2Cl2. The
CH2Cl2 extracts were dried, filtered and concentrated.
The residue was chromatographed on silica gel. Elution
with 4:1 hexanes–EtOAc gave 10 (0.65 g, 65%) as
yellow syrup: Rf 0.54 (3:2 hexanes–EtOAc); [h]D −15°
(c 1.24, CH2Cl2). Anal. Calcd for C10H11NO6S: C,
43.95; H, 4.06; N, 5.13. Found: C, 43.99; H, 4.05; N,
4.87.
under reduced pressure to afford a residue which was
chromatographed on silica gel to give 7 (0.145 g, 90%).
(c) From 13. To a solution of the thioacetate (13) (0.5
g, 1.71 mmol) in MeOH (5 mL) was added NaOMe
(0.092 g, 6 equiv). The mixture was stirred for 3 h at rt.
The solution was passed through ion-exchange resin
(Dowex 50×8-100 ion), filtered and concentrated. The
residue was chromatographed on silica gel to give 7
(0.25 g, 89%).
2,3-Di-O-acetyl-5-S-acetyl-5-thio-D-ribono-1,4-lac-
tone (11).—To a solution of 9 (0.5 g, 1.7 mmol) in
anhyd DMF (5 mL) was added potassium thioacetate
(0.23 g, 2 mmol). The mixture was stirred under an
inert atmosphere at rt for 10 min. The mixture was
filtered and concentrated under reduced pressure to
yield a crude product which was partitioned between
CH2Cl2 and water. The CH2Cl2 extracts were dried,
filtered and concentrated. The residue was chro-
matographed on silica gel. Elution with 4:1 hexanes–
EtOAc gave 11 (0.47 g, 95%) as a colorless syrup: Rf
0.54 (3:2 hexanes–EtOAc); [h]D −20° (c 0.66, CH2Cl2).
Anal. Calcd for C11H14O7S: C, 45.51; H, 4.86. Found:
C, 45.54; H, 4.96.
Acknowledgements
We thank the Conseil Regional de Picardie for finan-
cial support.
References
1. Robine, I.; Vogel, P.; Witezak, Z. N. Curr. Org. Chem.
2001, 34, 1117–1214.
2. Horton, D.; Wander, J. D. In The Carbohydrates; Chem-
istry and Biochemistry; Pigman, W.; Horton, D., Eds.,
2nd ed.; Academic: New York, 1980; Vol. IB, pp 799–
842.
3. Hashimoto, H.; Fujimori, T.; Yuasa, H. J. Carbohydr.
Chem. 1990, 9, 683–694.
4. Bellamy, F.; Barberousse, V.; Martin, N.; Masson, P.;
Millet, J.; Samreth, S.; Sepulchre, C.; Theveniaux, J.;
Horton, D. Eur. J. Med. Chem. 1995, 30, 101–115 and
references cited therein.
5. Capon, R. J.; Macleod, J. K. J. Chem. Soc., Chem.
Commun. 1987, 1200–1201.
6. Clayton, C. J.; Hughes, N. A. Carbohydr. Res. 1967, 4,
32–41.
7. Shin, J. E. N.; Perlin, A. S. Carbohydr. Res. 1979, 76,
165–176.
8. Anisuzzaman, A. K. M.; Whistler, R. L. Carbohydr. Res.
1977, 55, 205–214.
9. Hasegawa, A.; Kawai, Y.; Kasugai, H.; Kiso, M. Carbo-
hydr. Res. 1978, 63, 131–137.
10. (a) Trimnel, D.; Stout, E. I.; Doane, W. M.; Russell, C.
R. J. Org. Chem. 1975, 40, 1337–1339;
(b) Collins, P.; Ferrier, R. Monosaccharides. Their Chem-
istry and Their Roles in Natural Products; Wiley:
Chichester, 1995; pp 240–248.
11. Yuasa, H.; Izukawa, Y.; Hashimoto, H. J. Carbohydr.
Chem. 1989, 8, 753–763.
12. Fleetwood, A.; Hughes, N. A. Carbohydr. Res. 1999, 317,
204–209.
13. Bouchez, V.; Stasik, I.; Beaupere, D.; Uzan, R. Tetra-
hedron Lett. 1997, 38, 7733–7736.
14. Bouchez, V.; Stasik, I.; Beaupere, D.; Uzan, R. Carbo-
hydr. Res. 1997, 300, 139–142.
15. Dolhem, F.; Lievre, C.; Demailly, G. Tetrahedron Lett.
2002, 43, 1847–1849.
16. (a) Lerner, L. M. Methods Carbohydr. Chem. 1972, 6,
131–134;
2,3-Di-O-acetyl-5-S-acetyl-5-thio-
(13).—To 2,3-di-O-acetyl-5-S-acetyl-
D
-ribofuranose
-ribono-1,4-lac-
D
tone (11) (0.5 g,1.72 mmol) at 0 °C was added disiamyl-
borane freshly prepared16 (8 equiv) in THF. The
mixture was stirred, under an inert atmosphere, at rt
for 24 h. Then MeOH was added and the solution was
kept for 30 min and concentrated. The crude material
was diluted with CH2Cl2 and washed with water. The
CH2Cl2 extracts were dried, filtered and concentrated.
The residue was chromatographed on silica gel. Elution
with 4:1 hexanes–EtOAc gave 13 (0.292 g, 75%) as a
colorless syrup: Rf 0.34 (3:2 hexanes–EtOAc); [h]D
+8° (a/b=3:7). Anal. Calcd for C11H16O7S: C, 45.20;
H, 5.52. Found: C, 45.44; H, 6.28.
5-Thio- -ribopyranose (7).—(a) From 6. To a solu-
D
tion of the thiocyanate (6) (0.5 g, 2.16 mmol) in AcOH
(10 mL), at 110 °C was added activated zinc15 (1.7 g, 12
equiv). The mixture was stirred, under an inert atmo-
sphere, for 3 h. The solution was filtered and washed
with water, concentrated under reduced pressure to
afford a residue. The residue was subjected to flash
chromatography on silica gel. Elution with 9:1 then 4:1
CH2Cl2–MeOH gave 7 (0.21 g, 65%) as a colorless
syrup: Rf 0.59 (4:1 CH2Cl2–MeOH), lit.12: mp and
mixed mp 143–145 °C.6,12 Anal. Calcd for C5H10O4S:
C, 36.13; H, 6.06. Found: C, 36.16; H, 5.53.
(b) From 8. To 9:1 TFA–water (5 mL) was added
the thioribose derivative (8) (0.2 g, 0.97 mmol). The
solution was stirred for 15 min at rt and concentrated
(b) Brown, H. C.; Mandal, A. K.; Kulkarni, S. U. J. Org.
Chem. 1977, 42, 1392–1398.