Chemical interconversions of 4-cyanophenyl 1,5-dithio-β-D-xylopyranoside (Beciparcil): Structural modification at the C-4 position

Article abstract of DOI:10.1016/S0008-6215(98)00314-0

The title dithioxyloside 1, an orally active antithrombotic agent, as its 2,3-isopropylidene acetal, was converted into the corresponding glycos-4-ulose, which served as precursor via reduction to the 4-epimer of 1 and via oximation-reduction to the 4-acetamido-4-deoxy 4-epimer of 1. Copyright (C) 1998 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(98)00314-0

Carbohydrate Research 314 (1998) 161–167
Chemical interconversions of 4-cyanophenyl
1,5-dithio-b-
D
-xylopyranoside (Beciparcil®): structural
modification at the C-4 position
Yun Li a, Derek Horton a,*, Ve´ronique Barberousse b, Franc¸ois Bellamy b,
Patrice Renaut b, Soth Samreth b
a Department of Chemistry, The Ohio State Uni6ersity, Columbus, OH 43210, USA
b Laboratoires Fournier S.A., Centre de Recherche, 50 rue de Dijon, F-21121 Daix, France
Received 12 October 1998; accepted 4 November 1998
Abstract
The title dithioxyloside 1, an orally active antithrombotic agent, as its 2,3-isopropylidene acetal, was converted into
the corresponding glycos-4-ulose, which served as precursor via reduction to the 4-epimer of 1 and via oximation–re-
duction to the 4-acetamido-4-deoxy 4-epimer of 1. © 1998 Elsevier Science Ltd. All rights reserved.
Keywords: Xylosides; Dithio sugars; 1,5-Dithioxylosides; Antithrombotic agents
4-fluoro derivative of 1, and we now report
1. Introduction
results on the inversion of configuration at the
C-4 position and amination at C-4. The high
interest in structural modifications of this
dithioxyloside is manifested in recent work
from other laboratories [4].
As a part of a program to find venous
antithrombotic agents orally active in mam-
malian systems [1,2], we have identified 4-
cyanophenyl
1,5-dithio-b-
D
-xylopyranoside
The multiplicity of sensitive functional
groups present in 1 limits the range of chemi-
cal reagents that can be utilized for functional
transformations; most conventional oxidizing
and reducing reagents cannot be utilized. Fur-
thermore, the replacement of the ring oxygen
atom of sugars by sulfur leads to significant
changes in the behavior of these compounds.
The high nucleophilicity of sulfur in two envi-
ronments creates a great propensity for inter-
nal displacement of potential leaving-groups.
Despite these limitations, carefully regulated
procedures enabled the conversion of thiogly-
coside 1 into its corresponding 4-axial hy-
droxyl analogue 2 and its 4-axial 4-acetamido
analogue 3.
(Beciparcil, 1) as a particularly promising
compound, and its behavior in a range of
biological assays has been discussed in detail
[2]. With the goal of enhancing the biological
activity and evaluating structure–activity rela-
tionships, a range of synthetically modified
analogues have been prepared from 1. A pre-
vious paper [3] described the synthesis of the
2- and 4-monomethyl ethers and the 4-deoxy-
* Corresponding author. Present address: Department of
Chemistry, The American University, 4400 Massachusetts
Avenue NW, Washington, DC 20016, USA.
E-mail address: carbchm@american.edu (D. Horton)
0008-6215/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(98)00314-0

162
Y. Li et al. / Carbohydrate Research 314 (1998) 161–167
2. Results and discussion
The difficulties encountered in the preparation
of 5 and 6 evidently arise from participation
of the sulfur ring-atom to form an intermedi-
ate episulfonium ion 7 when a good leaving
group such as a triflate or a tosylate is present
at C-4. Similar instances have been previously
reported [6]. An intermediate such as 7 would
be prone to polymerization.
Although only a few methods for the spe-
cific protection of trans-disposed vicinal diols
in six-membered ring-systems are available in
the literature [5], we have shown that 1 can be
readily transformed into the readily separable,
crystalline 2,3- and 3,4-isopropylidene acetals
in 94% total yield [3]. The present work de-
scribes functional transformations of the 2,3-
acetal 4.
Application of the Mitsunobu reaction [7]
to the 2,3-acetal 4 did not afford the desired
inversion product 8. Isolated instead were
mainly the b-elimination product 9, along
with a small proportion of the simple acyla-
tion product 10 (when acetic acid was utilized,
R%=Me) (Scheme 1). The formation of 9 can
be accounted for by an elimination reaction
rather than substitution of the intermediate
11, because of the slightly acidic character of
the proton at C-5. When no acid was added to
the reaction, the formation of 9 reached 80%,
and thus would constitute an efficient method
for the preparation of 9 (Table 1).
Synthesis of 4-cyanophenyl 1,5-dithio-h- -
L
arabinopyranoside (2).—Attempts to convert
the 2,3-acetal 4 into the corresponding 4-trifl-
ate 5 from 4 by the action of triflic anhy-
dride–pyridine in dichloromethane led only to
a polymer-like, brown precipitate that was not
soluble in either organic solvents (ether, ethyl
acetate, or acetone) or water. The tosylate 6
(prepared with p-toluenesulfonyl chloride and
pyridine in dichloromethane) darkened (de-
composed) very rapidly in chloroform-d at
room temperature (rt) to form a dark-brown,
insoluble solid.
Different methods were tested for selective
oxidation of the hydroxyl function in 4 in the
Scheme 1.

Y. Li et al. / Carbohydrate Research 314 (1998) 161–167
163
Table 1
Attempted Mitsunobu reaction of the 2,3-acetal 4
Conditionsa
Time (h)
Product (%)
4
9
10
DEAD (6 equiv)–PPh3 (6 equiv)–PhCO2H (3.5 equiv)
DEAD (4 equiv)–PPh3 (4 equiv)–AcOH (4 equiv)
DEAD (2 equiv)–PPh3 (2 equiv)
50
28
15
0
70
0
31
0
80
0
25
0
a All reactions conducted in THF at rt.
presence of the two sulfur atoms. All attempts
to oxidize alcohol 4 to ketone 12 with chromi-
um(VI) oxidants such as pyridinium chloro-
chromate (PCC) or pyridinium dichlorochro-
mate (PDC) suffered from poor yields (15–
20%). However, the use of dimethyl sulfoxide
as oxidant gave better results. The best yield
was obtained with a Swern-type oxidation
(dimethyl sulfoxide–oxalyl chloride–triethy-
lamine [8]) conducted at low temperature
(Table 2).
Several reducing agents were tested for their
ability to selectively reduce the oxime 14 and
its acetate 15 to an amine in the presence of
the cyano group. For practical reasons, the
crude reduction product was acetylated di-
rectly (Ac2O–pyridine) and the acetamido
compound 16 was isolated by chromatogra-
phy on silica gel. The best result obtained
involved reduction of the free oxime 14 with
sodium borohydride–molybdenum trioxide
[9], which afforded 38% of the axial acetamide
16 along with 23% of the acetylated oxime 15
(resulting from the acetylation of the unre-
acted starting oxime 14). Other procedures,
for example sodium borohydride–nickel chlo-
ride hexahydrate [9], diborane–tetrahydro-
furan, sodium cyanoborohydride–TiCl3 [10],
and hydrogen–Raney nickel [11] gave less sat-
isfactory results. There was no detectable pro-
duction of the equatorial acetamide. Deace-
tonation of 16 under acidic conditions gave
the target acetamido product 3 in excellent
yield.
The reduction of 12 with sodium borohydride
took place from the less-hindered side to give
predominantly (91%) the 4-axial alcohol 13,
along with 5% of its 4-epimer 4. The 1H NMR
spectrum of 13 showed J3,4=2.1 Hz, as com-
pared with J3,4 =9.3 Hz for 4, indicating
clearly that the proton at C-4 in 13 was equa-
torial. Acidic hydrolysis of 13 gave the target
arabino analogue 2.
Compounds 2 and 3 were examined for
their ability to act as acceptors of
D
-galactose
using a partially purified galactosyltransferase
I from chick embryo [12]. Both were essen-
tially inactive at 5×10−3 M.
Synthesis of 4-cyanophenyl 4-acetamido-4-
deoxy-1,5-dithio-h- -arabinopyranoside (3).—
L
The glycos-4-ulose 12 was converted into its
oxime 14 with hydroxylamine hydrochloride–
pyridine in excellent yield (Scheme 2). It is
noteworthy that only one isomeric oxime was
3. Experimental
General methods.—TLC was performed on
precoated plates of Silica Gel 60F-254 (E.
Merck); components were detected by UV
light and by spraying the plates with 10%
H2SO4 and subsequent heating. Melting points
were determined with a Thomas–Hoover ap-
paratus and are uncorrected. Evaporation
were performed under diminished pressure.
Specific rotations were recorded with a
1
formed, as shown by the H NMR spectrum
of the crude product. The possibility of hydro-
gen bonding between the hydroxyl group of
the oxime and the O-3 atom suggests that the
configuration of the oxime is syn. Acetylation
of 14 [acetic anhydride–triethylamine–N,N-
dimethylaminopyridine (cat.)] gave the ace-
toxime 15 in 82% yield.

164
Y. Li et al. / Carbohydrate Research 314 (1998) 161–167
Table 2
Selective oxidation of the hydroxyl group of 4
Conditionsa
Temp. (°C)
Time (h)
Yield (%)
12
4
PCC (5 equiv)
PDC (4 equiv)
Me2SO (2 equiv)–TFAA (1.5 equiv)–Et3N (3 equiv)
Me2SO (3 equiv)–(COCl)2 (1.5 equiv)–Et3N (7 equiv)
rt
rt
20
72
0.5
0.5
15
18
33
65–75
47
53
25
0
−60 to −50
−60 to −45
a CH2Cl2 was the solvent in each experiment.
1
Perkin–Elmer 141 polarimeter. H and 13C
(305.40): C, 58.99; H, 4.95. Found: C, 58.98;
H, 4.97.
NMR spectra were recorded with a Bruker
AM-250 or AM-300 spectrometer, and chemi-
cal shifts refer to an internal standard of
Me4Si (l=0.00). Chemical-ionization (CI)
mass spectra were recorded at The Ohio State
University Chemical Instrument Center with
Kratos MS-30 and VG 70-250S mass spec-
trometers. Elemental analyses were performed
by Atlantic Microlabs, Atlanta, GA.
4-deoxy-2,3-O-isopropyli-
-threo-pent-4-eno-pyranos-
ide (9).—To a solution of 4-cyanophenyl 2,3-
O-isopropylidene-1,5-dithio-b- -xylopyranosi-
When 4 (69 mg, 0.21 mmol) was treated by
the same procedure with PPh3 (224 mg, 4
equiv), AcOH (38 mL, 4 equiv), and DEAD
(134 mL, 4 equiv) in THF (2 mL) for 28 h at
rt, only the starting 2,3-acetal 4 (48 mg, 70%)
and its 4-acetate 10 (19 mg, 25%) were
obtained.
4-Cyanophenyl 4-O-acetyl-2,3-O-isopropyli-
4-Cyanophenyl
dene-1,5-dithio-h-
dene - 1,5 - dithio - i- -xylopyranoside (10).—
D
This was obtained as a colorless oil; [h]D32
L
1
−39° (c 2.6, CHCl3); H NMR (250 MHz,
D
CDCl3): l 7.61 (m, 4 H, Ar), 5.04 (m, 1 H,
H-4), 4.32 (d, 1 H, J1,2 10.3 Hz, H-1), 3.70 (dd,
1 H, J2,3 8.7 Hz, H-2), 3.49 (dd, 1 H, J3,4 9.8
Hz, H-3), 2.92 (dd, 1 H, J4,5a 4.7, J5a,5b 13.3
Hz, H-5a), 2.69 (dd, 1 H, J4,5b 10.7 Hz, H-5b),
2.10 (s, 3 H, OAc), 1.48 (s, 3 H, Me), 1.45 (s,
3 H, Me); 13C NMR (63 MHz, CDCl3): l
169.9 (COCH3), 138.9 (Ar-C), 132.2 (Ar-CH),
131.6 (Ar-CH), 118.2 (Ar-C), 111.2 (CN),
109.0 (Me2CO2), 80.1, 78.7, 72.4 (C-2, 3, 4),
50.0 (C-1), 32.4 (C-5), 26.7 (Me), 26.6 (Me),
21.0 (COCH3). High-resolution MS: calcd for
C17H19NO4S2: m/z 365.0755; found: 365.0760.
4-Cyanophenyl 2,3-O-isopropylidene-1,5-di-
de [3] (4, 60 mg, 0.19 mmol) and PPh3 (97 mg,
2 equiv) in anhyd THF (2 mL) cooled to 0 °C
was added dropwise 59 mL (2 equiv) of di-
ethyl azodicarboxylate (DEAD, Aldrich) via a
syringe under argon. The cold bath was re-
moved and the mixture was stirred under ar-
gon for 15 h at rt. The solvent was evaporated
off and the crude product purified by chro-
matography over silica gel (1:4 Et2O–hexane)
to afford 9 as a colorless solid (45 mg, 80%),
mp (from EtOH) 97–99.5 °C, [h]1D9 −135° (c
1
1.0, CHCl3); H NMR (250 MHz, CDCl3): l
7.62 (m, 4 H, Ar), 5.97 (dd, 1 H, J3,5 1.5, J4,5
9.6 Hz, H-5), 5.88 (dd, 1 H, J3,4 2.4 Hz, H-4),
4.97 (d, 1 H, J1,2 10.9 Hz, H-1), 4.33 (ddd, 1
H, J2,3 8.4 Hz, H-3), 3.78 (dd, 1 H, H-2), 1.50
thio-h- -threo-pentopyranosid-4-ulose (12).—
L
To a solution of (COCl)2 (0.46 mL, 1.5 equiv)
in anhyd CH2Cl2 (10 mL) cooled to −60 °C
was added dropwise 0.745 mL (3 equiv) of
anhyd Me2SO via a syringe under argon. After
5 min at −60 °C, a solution of 1.132 g (3.5
mmol) of 4-cyanophenyl 2,3-O-isopropyli-
13
(s, 3 H, Me), 1.48 (s, 3 H, Me); C NMR (63
MHz, CDCl3): d 138.8 (Ar-C), 132.3 (Ar-CH),
132.2 (Ar-CH), 121.4, 119.9 (C-4, 5), 118.3
(Ar-C), 111.5 (Me2CO2), 111.4 (CN), 78.0,
77.2 (C-2, 3), 50.0 (C-1), 26.9 (Me), 26.7 (Me);
MS (EI): 305 (1.0, M+), 230 [6.9, M−
Me2C(OH)O], 113 (100, M−SC6H4CN−
Me2CO). Anal. Calcd for C15H15NO2S2
dene-1,5-dithio-b- -xylopyranoside [3] (4) in
D
anhyd CH2Cl2 (20 mL) was added dropwise
via a cannula needle. The temperature was
allowed to rise slowly to −45 °C (40 min) and

Y. Li et al. / Carbohydrate Research 314 (1998) 161–167
165
Scheme 2.
3.4 mL (7 equiv) of Et3N was then added at
−50 °C. The temperature was allowed to rise
to −25 °C (ꢀ30 min) and then water (30 mL)
was added and the cold bath removed. The
mixture was extracted with CH2Cl2 (3×100
mL) and the combined organic layer was
washed with 10% aq AcOH (2×20 mL), satu-
rated aq NaHCO3 (to pH 8), and water (2×30
mL), dried (MgSO4) and evaporated. The crude
product was purified by chromatography on
silica gel (2:3 EtOAc–hexane) to afford 12 as
a colorless solid (730 mg, 65%), mp (from
EtOAc–hexane) 161–162 °C, [h]1D8 +134.6° (c
equiv) during 10 min. After 1 h at 0 °C, 25% aq
AcOH (1 mL) was added and the solvents were
evaporated. Water (30 mL) was added to the
mixture, which was then extracted with EtOAc
(3×100 mL). The organic layer was washed
with saturated aq NaHCO3 (2×30 mL) and
then saturated aq NaCl (2×30 mL), dried
(MgSO4), and evaporated. The crude solid was
purified by chromatography over silica gel (1:1
–
EtOAc hexane) to afford the known 4 (30 mg,
5%) and its 4-epimer 13 as a colorless solid (549
mg, 91%), mp (from EtOAc–hexane) 131–
1
132 °C, [h]1D9 +17.0° (c 0.9, CHCl3); H NMR
1
(250 MHz, CDCl3): l 7.62 (m, 4 H, Ar), 4.55
(m, 1 H, H-4), 4.40 (d, 1 H, J1,2 10.5 Hz, H-1),
4.12 (dd, 1 H, J2,3 8.8 Hz, H-2), 3.43 (dd, 1 H,
J3,4 2.1 Hz, H-3), 3.11 (dd, 1 H, J4,5a 1.9, J5a,5b
14.5 Hz, H-5a), 2.75 (dd, 1 H, J4,5b 3.4 Hz,
H-5b), 2.30 (d, 1 H, J4,OH 4.0 Hz, OH, D2O
exchangeable), 1.47 (s, 6 H, 2×Me); 13C NMR
(63 MHz, CDCl3): l 139.9 (Ar-C), 132.3 (Ar-
CH), 130.8 (Ar-CH), 118.5 (Ar-C), 110.7
(Me2CO2), 108.7 (CN), 81.5, 73.3, 66.1 (C-2, 3,
4), 51.3 (C-1), 36.1 (C-5), 26.8 (Me), 26.6 (Me);
EIMS: 323 (0.6, M+), 248 [3.6, M−
Me2C(OH)O], 189 (2.6, M−SC6H4CN), 131
(70.6, M−SC6H4CN−Me2CO), 59 (100).
Anal. Calcd for C15H17NO3S2 (323.41): C,
55.70; H, 5.30. Found: C, 55.72; H, 5.35.
0.5, CHCl3); H NMR (200 MHz, CDCl3): l
7.65 (m, 4 H, Ar), 4.65 (d, 1 H, J1,2 10.1 Hz,
H-1), 4.23 (dd, 1 H, J2,3 9.6, J3,5a 1.0 Hz, H-3),
3.91 (dd, 1 H, H-2), 3.64 (dd, 1 H, J5a,5b 14.2
Hz, H-5a), 3.05 (d, 1 H, H-5b), 1.50 (s, 6 H,
13
2×Me); C NMR (63 MHz, CDCl3): l 195.0
(C-4), 138.0 (Ar-C), 132.4 (Ar-CH), 132.3 (Ar-
CH), 118.1 (Ar-C), 111.8 (Me2CO2), 111.3
(CN), 82.0, 81.1 (C-2, 3), 51.2 (C-1), 38.4 (C-5),
26.7 (Me), 26.3 (Me); EIMS: 321 (1.0, M+),
246 [4.3, M−Me2C(OH)O], 187 (26.2,
M−SC6H4CN), 129 (100, M−SC6H4-
CN−Me2CO). Anal. Calcd for C15H15NO3S2
(321.40): C, 56.05; H, 4.70. Found: C, 55.91; H,
4.67.
Table 2 details the outcome of other proce-
dures for oxidation of compound 4.
4-Cyanophenyl 1,5-dithio-h- -arabinopyran-
L
oside1 (2).—To a solution of the 2,3-acetal
4-Cyanophenyl 2,3-O-isopropylidene-1,5-di-
thio-h- -arabinopyranoside (13).—To a solu-
L
1 While this article was in press, a synthesis of this com-
pound by a different route was reported [E. Bozo´, S. Boros,
J. Kuszmann, Carbohydr. Res., 311 (1998) 191–202], giving
NMR data essentially identical to those reported here.
tion of the glycosidulose 12 (600 mg, 1.87
mmol) in MeOH (30 mL) and CH2Cl2 (15 mL)
cooled to 0 °C was added NaBH4 (71 mg, 1

166
Y. Li et al. / Carbohydrate Research 314 (1998) 161–167
mL) cooled to 0 °C was added 108 mL (4
equiv) of Et3N, 37 mL (2 equiv) of Ac2O, and
4-dimethylaminopyridine (DMAP, catalytic
amount). The cold bath was removed, the
solution was stirred for 15 h at rt, CH2Cl2 (30
mL) was added, and the mixture was washed
with water (3×5 mL). The organic layer was
dried (MgSO4), and evaporated. The crude
product was purified by chromatography over
silica gel (1:1 EtOAc–hexane) to afford 15 as
a colorless oil (60 mg, 82%); [h]2D0 +62° (c 0.8,
13 (107 mg, 0.33 mmol) in MeOH (5 mL) was
added Amberlite IR-120 (H+) resin (ꢀ20
mg), and the mixture was vigorously stirred
for 17 h at rt. Removal of the resin by filtra-
tion through Celite and evaporation of MeOH
gave a pale-yellow solid that was washed with
ether (2×3 mL) to afford 2 as a colorless
solid (86 mg, 92%); mp (from EtOAc) 215–
1
217 °C, [h]2D0 −52° (c 0.2, MeOH); H NMR
(250 MHz, Me2SO-d6/D2O): l 7.76 (d, 2 H, J
8.5 Hz, Ar), 7.55 (d, 2 H, Ar), 4.41 (d, 1 H,
J1,2 7.1 Hz, H-1), 4.01 (m, 1 H, H-4), 3.89 (t,
1 H, J2,3 7.0 Hz, H-2), 3.43 (m, 1 H, H-3), 2.71
(d, 2 H, J4,5 4.6 Hz, H-5); EIMS: 283 (0.9,
M+), 149 (23.6, M−SC6H4CN), 135 (69.6,
HSC6H4CN), 131 (100, M−SC6H4CN−
H2O). Anal. Calcd for C12H13NO3S2 (283.35):
C, 50.86; H, 4.62. Found: C, 50.68; H, 4.47.
4-Cyanophenyl 2,3-O-isopropylidene-1,5-di-
1
CHCl3); H NMR (300 MHz, CDCl3): l 7.63
(m, 4 H, Ar), 4.54 (d, 1 H, J1,2 10.2 Hz, H-1),
4.17 (d, 1 H, J2,3 9.1 Hz, H-3), 3.96 (d, 1 H,
J5a,5b 14.9 Hz, H-5a), 3.86 (dd, 1 H, H-2), 3.29
(d, 1 H, H-5b), 2.20 (s, 3H, CH3CO), 1.53 (s,
3 H, Me), 1.52 (s, 3 H, Me); 13C NMR (63
MHz, CDCl3): l 167.6 (CH3CO), 157.2 (C-4),
138.1 (Ar-C), 132.3 (Ar-CH), 132.2 (Ar-CH),
118.1 (Ar-C), 111.6 (CN, Me2CO2), 81.3, 78.1
(C-2, 3), 50.7 (C-1), 26.6 (C-5, 2×Me), 19.4
(CH3CO); MS (EI): 378 (0.1, M+), 202 (6.2,
M−SC6H4CN−Ac+1), 126 [3.6, M−
SC6H4CN−Ac−Me2C(OH)O], 43 (100, Ac).
High-resolution MS: calcd for C17H18N2O4S2:
m/z 378.0708; found: 378.0699.
thio-h- -threo-pentopyranosid-4-ulose oxime
L
(14).—To a suspension of the glycos-4-ulose
12 (102 mg, 0.32 mmol) and NH2OH·HCl
(45 mg, 2 equiv) in MeOH (5 mL) cooled to
0 °C was added dropwise 54 mL (2.1 equiv) of
pyridine. The cold bath was removed and the
solution was stirred for 1.5 h at rt. Ethyl
acetate (50 mL) was added and the mixture
was washed with water (3×15 mL). The or-
ganic layer was dried (MgSO4), and evapo-
rated to afford 14 as a pure (NMR), colorless
solid (105 mg, 98%), mp (from EtOAc–hex-
ane) 192–190 °C (dec.), [h]1D9 +121° (c 0.4,
4-Cyanophenyl 4-acetamido-4-deoxy-2,3-O-
isopropylidene-1,5-dithio-h- -arabinopyranosi-
L
de (16).—To a suspension of the oxime 14
(130 mg, 0.39 mmol) in MeOH (4 mL) cooled
to 0 °C was added 78 mg (1.4 equiv) of MoO3
[9] and 206 mg (14 equiv) of NaBH4. The cold
bath was removed and the mixture was stirred
for 2 h at rt. Then added at 0 °C were 56 mg
(1 equiv) of MoO3 and 147 mg (10 equiv) of
NaBH4. After 2 h at rt, 10% aq AcOH (1 mL)
was added to decompose the excess of NaBH4,
concd NH4OH (1 mL) was then added, and
the solvents were evaporated off under dimin-
ished pressure. Water (5 mL) was added to the
mixture, which was then extracted with
CH2Cl2 (3×40 mL). The organic layer was
dried (MgSO4), and evaporated.
1
CHCl3); H NMR (250 MHz, CDCl3): l 7.75
(b, 1H, OH), 7.63 (m, 4 H, Ar), 4.52 (d, 1 H,
J1,2 10.1 Hz, H-1), 4.07 (d, 1 H, J2,3 9.1 Hz,
H-3), 4.05 (d, 1 H, J5a,5b 14.8 Hz, H-5a), 3.81
(dd, 1 H, H-2), 3.18 (d, 1 H, H-5b), 1.51 (s, 6
H, 2×Me); 13C NMR (63 MHz, CDCl3): l
149.5 (C-4), 138.7 (Ar-C), 132.2 (Ar-CH),
131.8 (Ar-CH), 118.2 (Ar-C), 111.2 (CN),
111.1 (Me2CO2), 81.4, 78.2 (C-2, 3), 50.6 (C-
1), 26.7 (Me), 26.5 (Me), 25.0 (C-5); MS (EI):
336 (0.1, M+), 261 [2.8, M−Me2C(OH)O],
202 (6.6, M−SC6H4CN), 135 (77.8, HSC6-
H4CN), 43 (100). Anal. Calcd for C15H16-
N2O3S2 (336.41): C, 53.55; H, 4.79. Found: C,
53.48; H, 4.85.
The crude oil was dissolved in CH2Cl2 (5
mL), and then were added 188 mL (6 equiv) of
pyridine and 110 mL (3 equiv) of Ac2O. After
16 h at rt, all solvents were evaporated off and
the crude product was purified by chromatog-
raphy over silica gel (2:3–4:1 EtOAc–hexane)
to afford the known 15 (33 mg, 23%) and the
4-acetamido derivative 16 as a colorless solid
(53 mg, 38%), mp (from EtOAc–hexane)
4-Cyanophenyl
4-acetoximino-2,3-O-iso-
-threo-pentopyrano-
propylidene-1,5-dithio-h-
L
sid-4-ulose (15).—To a solution of the 4-
oxime 14 (65 mg, 0.19 mmol) in CH2Cl2 (2

Y. Li et al. / Carbohydrate Research 314 (1998) 161–167
167
152.5–153.5 °C, [h]1D8 +48° (c 0.5, CHCl3); 1H
NMR (300 MHz, CDCl3): l 7.61 (m, 4 H,
Ar), 6.05 (bd, 1H, J4,NH 7.4 Hz, NH), 4.92 (m,
1 H, H-4), 4.39 (d, 1 H, J1,2 10.4 Hz, H-1),
3.82 (dd, 1 H, J2,3 9.1 Hz, H-2), 3.52 (dd, 1 H,
J3,4 3.4 Hz, H-3), 3.12 (dd, 1 H, J4,5a 2.7, J5a,5b
14.5 Hz, H-5a), 2.78 (dd, 1 H, J4,5b 3.1 Hz,
H-5b), 2.08 (s, 3H, Ac), 1.46 (s, 3H, Me), 1.45
(s, 3 H, Me); 13C NMR (75 MHz, CDCl3): l
170.1 (CH3CO), 139.8 (Ar-C), 132.3 (Ar-CH),
130.2 (Ar-CH), 118.3 (Ar-C), 110.6 (CN),
108.8 (Me2CO2), 79.5, 74.6 (C-2, 3), 51.2 (C-
1), 46.8 (C-4), 34.8 (C-5), 26.6 (Me), 26.5
(Me), 23.4 (CH3CO); EIMS: 364 (0.6, M+),
305 (1.1, M−AcNH), 247 (3.8, M−
AcNH−Me2CO), 230 (4.0, M−SC6H4CN),
172 (41.5, M−SC6H4CN−Me2CO), 135
(23.0, HSC6H4CN), 43 (100, Ac). Anal. Calcd
for C17H20N2O3S2 (364.46): C, 56.02; H, 5.53.
Found: C, 55.76; H, 5.45.
M−OH), 173 (12.3, M−OH−SC6H4CN),
132 (14.8, M−AcNH−SC6H4CN), 43 (100,
Ac). Anal. Calcd for C14H16N2O3S2 (324.40):
C, 51.83; H, 4.97; N, 8.63. Found: C, 51.90;
H, 5.05; N, 8.23.
References
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4-Cyanophenyl
4-acetamido-4-deoxy-1,5-
dithio-h- -arabinopyranoside (17).—To a so-
L
lution of the 2,3-acetal 16 (208 mg, 0.57
mmol) in MeOH (15 mL) was added Amber-
lite IR-120 (H+) resin (ꢀ20 mg), and the
mixture was vigorously stirred for 17 h at rt,
then 3 h at reflux. Removal of the resin by
filtration through Celite and evaporation of
MeOH gave a pure (NMR), colorless solid
(178 mg, 96%), mp (from MeOH–Et2O) 199–
1
200 °C, [h]2D0 −158° (c 0.1, MeOH); H NMR
[8] A.J. Manuso, D. Swern, Synthesis, (1981) 165–185.
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(250 MHz, CD3OD): l 7.61 (m, 4 H, Ar), 4.51
(m, 1 H, H-4), 4.34 (d, 1 H, J1,2 7.2 Hz, H-1),
4.02 (t, 1 H, J2,3 7.2 Hz, H-2), 3.68 (dd, 1 H,
J3,4 3.6 Hz, H-3), 2.88 (dd, 1 H, J4,5a 6.7, J5a,5b
13.8 Hz, H-5a), 2.75 (dd, 1 H, J4,5b 2.7 Hz,
H-5b), 2.01 (s, 3H, Ac); MS (EI): 307 (0.1,
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.