New 1-C-(5-thio-D-xylopyranosyl) derivatives as potential orally active venous antithrombotics

Article abstract of DOI:10.1016/S0008-6215(03)00147-2

In the search for new orally active antithrombotic drugs that are metabolically stable, we explored the synthesis of 1-C-(5-thio-D-xylosyl) derivatives, examining radical and nucleophilic methods. Thus synthesized were aryl, benzyl, alkylcarboxymethylenyl, arylsulfonylmethylenyl and alkylaminocarboxymethylenyl C-linked analogues of 5-thio-D-xylopyranosides.

Full text of DOI:10.1016/S0008-6215(03)00147-2

Carbohydrate Research 338 (2003) 1271ꢀ1282
/
www.elsevier.com/locate/carres
New 1-C-(5-thio-
D-xylopyranosyl) derivatives as potential orally
active venous antithrombotics
Laurent Mignon,a Christophe Goichot,a Philippe Ratel,a Ge´rald Cagnin,b
Michel Baudry,b Jean-Pierre Praly,b Benaıssa Boubia,a Ve´ronique Barberoussea,*
¨
a Laboratoires Fournier, 50 rue de Dijon, 21121 Daix, France
b Laboratoire de Chimie Organique II, Universite´ C. Bernard Lyon 1, Unite´ Associe´e au CNRS 5622, CPE-Lyon, 43, bd du 11 Novembre 1918, 69622
Villeurbanne, France
Received 2 October 2002; accepted 1 March 2003
Abstract
In the search for new orally active antithrombotic drugs that are metabolically stable, we explored the synthesis of 1-C-(5-thio-
xylosyl) derivatives, examining radical and nucleophilic methods. Thus synthesized were aryl, benzyl, alkylcarboxymethylenyl,
D-
arylsulfonylmethylenyl and alkylaminocarboxymethylenyl C-linked analogues of 5-thio-D-xylopyranosides.
# 2003 Elsevier Science Ltd. All rights reserved.
Keywords: 1-C-(5-Thio-D-xylopyranosyl) derivatives; Venous antithrombotics; Glycosidic linkage
1. Introduction
substrates for glucuronosyltransferase (EC 2.4.1.17) and
were shown to undergo metabolic cleavage of the
glycosidic linkage in vitro and in vivo.7
The prophylaxis of thromboembolic disorders (a major
cause of morbidity and mortality in industrialized
countries) is largely managed by intravenous heparin
therapy (which has drawbacks associated with the mode
of administration and hemorrhagic risk) or by oral
warfarin therapy (which has a delayed onset of action,
presents a risk of bleeding and interactions with
numerous drugs). In the search for new orally active
antithrombotic drugs without such serious side-effects
as bleeding, we have been developing, for the past 10
years, a ‘xylosides’ program. This program is based on
the hypothesis that b-
D-xylopyranosides might be effec-
tive antithrombotic drugs1ꢀ4 since they induce biosynth-
esis of glycosaminoglycans in cell cultures, as
demonstrated by Okayama,5 Schwarz6 and others.
Three representatives of this novel family have been
evaluated in clinical trials (Naroparcil, Beciparcil, Ili-
parcil) and have demonstrated significant pharmacolo-
gical properties. All three compounds proved to be good
In order to obtain derivatives that are more metabo-
D-
xylopyranosyl) analogues. Since little was known about
the synthesis of such derivatives, we investigated various
pathways to this class of sugar derivatives.
lically stable, we set out to synthesize 1-C-(5-thio-b-
2. Results and discussion
* Corresponding author.
address:
Among known methods for synthesis of C-glycosyl
compounds,8ꢀ16 not all were successful. We began with
E-mail
(V. Barberousse).
v.barberousse@fournier.fr
0008-6215/03/$ - see front matter # 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0008-6215(03)00147-2

1272
L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ1282
/
2,3,4-tri-O-benzyl-5-thio-D-xylonolactone (4), as Lo-
pez17 and Boyd18 did for 5-O-analogues. Lactone 4
Methods utilizing silylated enol ethers, as employed
by Hanessian34 with glycosyl halides and by Schmidt35
with sugar trichloroacetimidates (Scheme 4) gave more
satisfactory results.
could be readily synthesized from methyl 5-thio-D-
xylopyranoside (1)19 by standard methods20a via inter-
mediates 220b and 3 (Scheme 1). Attempted transforma-
tion of lactone 4, by methods of Lopez and Boyd’s was
unsuccessful. Failure to obtain the anion derived from
the 7-bromomethyl-4-methyl-2H-1-benzopyran-2-one
by metallation at C-11 with Mg was the main obstacle
Table 1 summarizes the results. This strategy proved
promising as it can lead to several products (such as
compounds 16 and 17), albeit in low yield. The J1,2
coupling constants supported the b anomeric configura-
tions (see Table 1).
(magnesiumꢀrefluxing Et2O or highly activated magne-
/
Phenylsulfonyl and phenylcarbamide derivatives are
also investigated. Most methods for the synthesis of C-
glycosyl compounds use protected sugar derivatives,
except for that of Davidson and co-workers36 who
devised a method in which a Wittig-type reagent reacts
with an unprotected sugar. Conventional methods for
the synthesis of tetrahydropyran derivative using sugars,
require protection of the hydroxyl groups. Davidson
and co-workers reported a sodium salt of a phosphonate
sulfone that reacts in a Wittig manner with unprotected
sugars to yield, after treatment with base, exclusively the
corresponding b tetrahydropyrans.
sium anthracene in THF at room temperature and
under reflux according to Gallagher21 were the two
methods applied without success).
We next attempted to synthesize 2,3,4-tri-O-acetyl-5-
thio-b-D-xylopyranosyl cyanide, which could potentially
lead to either nitrogen- or oxygen-based functional
groups (amide, amine, acid, alcohol).22 The procedures
used, using the acetylated glycosyl bromide22,23 and
Hg(CN)2 or using the b-tetraacetate24ꢀ29 and trimethyl-
silyl cyanide, failed to yield the target compound and led
mainly respectively to a hemithioacetal or a 2-deacety-
lated product.
In this manner, thioxylosyl derivatives were synthe-
sized from the free 5-thioxylose and the diethylaryl
sulfonylmethyl phosphonate (Scheme 5).37,38
Attempted radical synthesis from bromide 5 and
acrylonitrile, as described by Giese,30 did not give the
desired product 6; instead while 7 was the major product
(Scheme 2).
In the method described by Davidson and co-workers,
the final mixture of a and b anomers was acetylated and
then deacetylated to afford the b-anomer exclusively (is
a retro-Michael reaction at the deacetylation step in the
case of the O-sugars). This was not observed with the 5-
thio sugars studied. Thus peracetylated a and b isomers
had to be separated and then deacetylated to yield the
desired compounds 18a and 18b (in 7.3 and 5.5% yields
Reaction of bromide 5 with an aryl cuprate, as
described by Tucker,31 also failed to form the target
product; only 2-deoxy-acetylated derivative 7 was ob-
tained (Scheme 3), supporting previous findings.32
Use of Grignard reagents and bromide 5, following
Panigot and co-workers,33 led to compounds 9 and 11 as
white crystals (Scheme 2), but the yields were modest (15
and 35%, respectively). The J1,2 coupling constants of
10.1 and 10.6 Hz supported the b anomeric configura-
tions.
from 5-thio-D-xylopyranose) as white powders (Scheme
5). The J1,2 coupling constants of 5 and 9.5 Hz
supported the anomeric configurations.
Scheme 1.

L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ
/
1282
1273
Scheme 2.
cyclized to yield 22. In the case of the corresponding O-
xyloside, the a,b-unsaturated ester obtained by the
Wittig reaction did not cyclize immediately but required
a cyclization step in basic media.40 Aminolysis of the
ester using 4-aminobenzonitrile led to the desired
product (Scheme 6). Derivative 23b was obtained in
Scheme 3.
9% yield from 5-thio-D-xylopyranose. The J1,2 coupling
constant of 9.5 Hz supported the anomeric configura-
tion.
The Wittigꢀ
/
Horner reaction conditions used by
Davidson and co-workers36 were modified to yield a
mixture of anomers (a/b: 70/30 as shown in Scheme 5).
The acetylation separation sequence yielded the isomeric
compounds 21b and 21a, which were deacetylated to
form products 20b and 20a under mild reaction condi-
tions that avoid anomerization (by the retro-Michael
reaction because of the acidic a-hydrogen of the
arylsulfonyl group). Compounds 20a and 20b were
obtained as white powders in 9 and 3% yields from 5-
All products were studied in Wessler’s rat model for
venous thrombosis.41 In these experiments, factor Xa is
the thrombogenic agent, with thrombosis being studied
4 h after oral administration of the product. Only 15b,
16b, and 17b demonstrated activities similar to that of
Beciparcil. Surprisingly, compound 16b was extensively
metabolized in in vitro studies with human microsomes8
and so could not be evaluated in clinical trials.
thio-D-xylopyranose. The J1,2 coupling constants of 5
and 9.5 Hz supported the anomeric configurations.
We were also interested in preparing another type of
C-thioxylose analogue of Beciparcil, which was obtained
by using a Wittig reaction (Scheme 6). The reaction
conditions described by Fraser-Reid and co-workers39
did not give the expected compounds; use of pyridine as
solvent afforded the Wittig adduct, which immediately
3. Experimental
3.1. General methods
TLC was performed on precoated plates of Silica gel 60-
254-F; components were detected by UV light and by
spraying the plates with 10% H2SO4 and subsequent

1274
L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ
/
1282
Scheme 4.
heating. Melting points were determined with Kofler
apparatus and are uncorrected. Specific rotations were
(MgSO4), and concentrated under diminished pressure.
The residue was purified by flash chromatography on
recorded with a Perkinꢀ
Elmer 241 polarimeter. 1H
NMR spectra were recorded with a Bruker ACP-300
/
silica gel with 9:1 tolueneꢀ
/
EtOAc to give methyl 2,3,4-
-xylopyranoside20b (2, 16.75 g,
tri-O-benzyl-5-thio-D
79%) as white crystals, mp 66 8C; [a]D28
spectrometer and chemical shifts refer to an internal
ꢂ118 (c 0.67,
/
1
standard of Me4Si (dꢁ/0.00). Elemental analyses were
MeOH); H NMR (300 MHz, CDCl3): d 2.44 (m, 1 H,
H-5), 2.76 (m, 1 H, H-5), 3.41 (s, 1.41 H, CH3a), 3.55 (s,
1.59 H, CH3b), 3.73 (m, 3 H, H-2,3,4), 4.32 (d, 0.47 H,
J1,2 1.2 Hz, H-1a), 4.40 (d, 0.53 H, J1,2 8.6 Hz, H-1b),
4.75 (m, 6 H, CH2Ph), 7.32 (m, 15 H, Ph).
performed with a Perkinꢀ/Elmer CHN 2400 instrument.
3.2. 2,3,4-Tri-O-benzyl-5-thio-D-xylonolactone (4)
A solution of 220b (1 g, 2.2 mmol) and 1 M H2SO4 in
AcOH (30 mL) was heated at 100 8C with stirring. One
hour later, the mixture was poured into ice. The solution
was extracted with CH2Cl2, the organic layer washed
with brine, dried (MgSO4), and concentrated under
diminished pressure. The residue was purified by flash
Potassium hydroxide (52 g, 0.93 mol) and benzyl
bromide (79.6 g, 0.46 mol) were added slowly to a
solution of methyl 5-thio-D
-xylopyranoside19 (1, 8.39 g,
46.6 mmol) in tetrahydrofuran (100 mL). The solution
was refluxed for 4 h, cooled and then poured into 1 M
aq HCl. This mixture was extracted with Et2O. The
organic layer was washed twice with water, dried
chromatography on silica gel with 12:1 tolueneꢀEtOAc
/

L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ
/
1282
1275
Table 1
Results of the silylated enol ethers strategy (A, 5ꢂ
13ꢂMe3SiOTf)
A solution of 3 (500 mg, 1.15 mmol) and Ac2O (1.5
mL) in Me2SO (5 mL) was stirred20 for 48 h. The
mixture was then extracted with Et2O. The organic layer
was diluted with CCl3CH3, washed with water, dried
(MgSO4) and concentrated under diminished pressure.
The product 4 was obtained by precipitation with ether
/Zn Cl2; B,
/
as white crystals; mp 120 8C; [a]D28
ꢃ18 (c 0.3, 1:1
/
1
Me2SO); H NMR (300 MHz, CDCl3): d 3.21
MeOHꢀ
/
(dd, 1 H, J5,5? 12 Hz, J4,5 3.8 Hz, H-5eq), 3.86 (m, 1 H,
H-3), 4.0 (m, 1 H, H-4), 4.12 (d, 1 H, J2,3 6 Hz, H-2),
4.41 (m, 1 H, H-5ax), 4.53 (m, 5 H, CH2Ph), 4.85 (d, 1
H, J 11.7 Hz, CH2Ph), 7.31 (m, 15 H, Ph). Anal. Calcd
for C26H26O4S: C, 71.86; H, 6.03. Found: C, 71.19; H,
5.70.
3.3. 1,5-Anhydro-2,3,4-tri-O-acetyl-5-thio-D-xylitol (7)
Acrylonitrile (987 mL, 15 mmol) and then tributyltin
hydride (960 mg, 3.3 mmol) were added dropwise to a
suspension of bromide 5 (1.065 g, 3 mmol) in ether (6
mL). After 24 h of irradiation with a sun lamp (750 W),
the mixture was concentrated under diminished pres-
sure. The residue was purified by flash chromatography
to give 2,3,4-tri-O-benzyl-5-thio-D-xylopyranose (3, 760
mg, 79%) as white crystals; mp 68 8C; [a]D28
MeOH); H NMR (300 MHz, Me2SO): d 2.79 (m, 2 H,
H-5), 3.6 (m, 3 H, H-2,3,4), 4.77 (m, 6 H, CH2 Ph), 4.9
(d, 0.15 H, J1,2 11 Hz, H-1b), 5.08 (s, 0.85 H, H-1a), 7.31
(m, 15 H, Ph). Anal. Calcd for C25H27O4S: C, 70.89; H,
6.43. Found: C, 70.91; H, 6.47.
ꢂ18 (c 1.4,
/
1
on silica gel with 5:1 tolueneꢀEtOAc to give 7 as white
/
solid (345 mg, 42%); mp 129 8C; [a]2D3 08 (c 1, CDCl3); 1H
NMR (300 MHz, Me2SO): d 1.98 (s, 9 H, OAc), 2.7 (m,
Scheme 5. (i) Rꢁ
/
H/NaHMDS, pyr, 100 8C, 15 min, 30%, 18, a/bꢁ
/
50/50; (ii) Rꢁ
/
CN/NaH, pyr, 10 h, 5 8C, 31%, 20, a/bꢁ70/30;
/
(iii) Ac2O, pyr; (iv) chromatography; (v) NaOMe, MeOH.

1276
L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ1282
/
Scheme 6.
72.9 (C-5), 74.4 (C-3), 75.6 (C-4), 126ꢀ137 (Ph), 169
(CO). Anal. Calcd for C18H22O6S: C, 59.00; H, 6.05.
4 H, CH2), 4.8 (m, 2 H, H-2, H-4), 5.05 (t, 1 H, J 9.6 Hz,
H-3). Anal. Calcd for C11H16O6S: C, 47.82; H, 5.84.
Found: C, 47.77; H, 5.88.
/
Found: C, 59.52; H, 5.80.
Sodium methoxide (8.8 mg, 0.16 mmol) was added to
a suspension of compound 8 (600 mg, 1.63 mmol) in
MeOH (25 mL) and the mixture stirred for 1.5 h at rt.
The mixture was then neutralized with Amberlite† IR-
120 (Hꢂ). Filtration and lyophilisation of the solution
3.4. a-(5-Thio-b-D-xylopyranosyl)-toluene (9)
Benzyl chloride (20 mL, 0.174 mol) in ether (100 mL)
was added dropwise to a suspension of magnesium
turnings (5 g, 0.205 mol) in ether (50 mL) for 30 min at
room temperature (rt). After refluxing for 2 h, a solution
of bromide 5 (4.26 g, 12 mmol) in ether (100 mL) was
added dropwise during 30 min to the Grignard reagent.
The mixture was boiled under reflux for 3 h and then
poured into iced water and AcOH. After stirring, the
organic layer was concentrated and the residue was
treated with Ac2O (50 mL), pyridine (50 mL) and small
amounts of 4-dimethylaminopyridine. The mixture was
stirred overnight, poured into iced 1 M HCl (800 mL)
and extracted with ether. The dried extract was evapo-
rated and the residue purified by flash chromatography
gave compound 9 (295 mg, 75%); mp 103 8C; [a]D24
ꢂ178
/
1
(c 0.2, Me2SO); H NMR (300 MHz, Me2SO): d 2.76
(m, 1 H, H-4), 2.85 (m, 3 H), 2.91 (m, 1 H, H-2), 3.1 (m,
1 H, H-3), 3.34 (s, 2 H), 4.89 (d, 1 H, J 4.2 Hz, OH), 5.01
(d, 1 H, J 4.5 Hz, OH), 5.11 (d, 1 H, J 5.2 Hz, OH), 7.20
(m, 5 H, Ph). Anal. Calcd for C12H16O3S; 0.39 H2O: C,
58.27; H, 6.84. Found: C, 58.16; H, 6.64.
3.5. (5-Thio-b-D-xylopyranosyl)benzene (11)
A solution of 7 g (19.7 mmol) of the bromide 5 in ether
(200 mL) was added dropwise during 30 min to
phenylmagnesium bromide (43 g, 0.24 mol) in ether
(180 mL). The mixture was refluxed for 3 h and then
poured into iced water and AcOH. After stirring, the
organic layer was concentrated and the residue was
treated with Ac2O (50 mL), pyridine (60 mL) and small
amounts of 4-dimethylaminopyridine. The mixture was
stirred overnight, poured into iced 1 M HCl and
extracted with ether. After concentrating under de-
creased pressure, the residue was purified by flash
on silica gel with 8:1 tolueneꢀ
O-acetyl-5-thio-b- -xylopyranosyl)toluene (8), mp
164 8C; [a]2D8
48 (c 0.3, MeOH); H NMR (300 MHz,
/
EtOAc to give a-(2,3,4-tri-
D
1
ꢂ
/
Me2SO): d 1.96 (s, 9 H, OAc), 2.4 (m, 1 H, CH2), 2.67
(m, 1 H, H-5eq), 2.81 (m, 1 H, H-5ax), 3.0 (m, 1 H,
CH2), 3.45 (m, 1 H, H-1), 4.82 (m, 1 H, H-4), 4.94 (t, 1
H, J 10.1 Hz, H-2), 5.08 (t, 1 H, J 9.5 Hz, H-3), 7.26 (m,
5 H, Ph); 13C NMR (60 MHz, CDCl3): d 20.6
(CH3CO2), 30.0 (CH2S), 36.8 (CH2Ph), 46.6 (C-2),

L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ
/
1282
1277
chromatography on silica gel using 9:1 tolueneꢀ
/EtOAc
Hz, J3,4 9.7 Hz, H-3), 5.22ꢀ/5.06 (m, 2 H, H-2,4), 3.67
as eluent to give compound 10 as white crystals (2.4 g,
1
(ddd, 1 H, J1,2 10.1 Hz, H-1), 3.18 (dd, 1 H, J 5 and 17
35%); mp 191 8C; [a]D22
(300 MHz, Me2SO): d 1.63ꢀ
ꢂ
/
28 (c 0.46, MeOH); H NMR
Hz, CH2), 3.01 (dd, 1 H, J 7.7 Hz, CH2), 2.91ꢀ2.7 (m, 2
/
/
2.5 (m, 9 H, OAc), 2.84 (m,
H, H-5), 2.03 (s, 3 H, OAc), 2.01 (s, 3 H, OAc), 1.89 (s, 3
H, OAc). Anal. Calcd for C19H22O7S: C, 57.86; H, 5.62.
Found: C, 57.84; H, 5.65.
1 H, H-5eq), 3.07 (m, 1 H, H-5ax), 4.35 (d, 1 H, J1,2 10.6
Hz, H-1), 5.03 (m, 1 H, H-4), 5.18 (t, 1 H, H-3), 5.36 (t, 1
H, H-2), 7.3 (m, 5 H, Ph). Anal. Calcd for C17H20O6S:
C, 57.94; H, 5.72. Found: C, 58.06; H, 5.63.
Compound 15a formed as white crystals (99% yield);
1
mp 174 8C; [a]2D1
ꢂ
/
308 (c 0.6, pyridine); H NMR (300
To a suspension of compound 10 (1 g, 2.86 mmol) in
MeOH (25 mL) was added NaOMe (30.8 mg, 0.57
mmol). After stirring during 2 h the mixture was
neutralized with Amberlite† IR-120 (Hꢂ). Filtration
followed by flash chromatography on silica gel with 10:1
MHz, C5D5N): d 8.17 (d, 2 H, J 7 Hz, Ar), 7.47 (t, 1 H,
J 7 Hz, Ar), 7.4 (t, 2 H, J 7 Hz, Ar), 4.31 (m, 1 H, J4,5e
5.9 Hz, J4,5a 8.9 Hz, H-4), 4.23 (dd, 1 H, J 3.9 and 16.5
Hz, CH2), 4.1 (dd, 1 H, J2,3 8.3 Hz, H-2), 3.97 (ddd, 1 H,
J1,2 10 Hz, H-1), 3.86 (t, 1 H, H-3), 3.3 (dd, 1 H, J 8.5
CH2Cl2ꢀ
/
MeOH gave compound 11 as white crystals
478 (c 0.5, MeOH);
Hz, CH2), 3.1ꢀ
C13H16O4S: C, 58.19; H, 6.01. Found: C, 57.94; H, 5.99.
/
2.92 (m, 2 H, H-5). Anal. Calcd for
(459 mg, 71%); mp 195 8C; [a]D21
ꢂ
/
1H NMR (300 MHz, Me2SO): d 2.59 (m, 2 H, H-5), 3.03
(m, 1 H, H-2), 3.5 (m, 1 H, H-4), 3.65 (m, 2 H, H-3,1),
4.76 (d, 1 H, J 4 Hz, OH), 4.96 (d, 1 H, J 5 Hz, OH),
5.12 (d, 1 H, J 5 Hz, OH), 7.29 (m, 5 H, Ph). Anal.
Calcd for C11H14O3S: C, 58.38; H, 6.23. Found: C,
58.09; H, 6.23.
3.6.1.3. 3,7-Anhydro-2,2-dimethyl-4-thio-
heptonic acid, g-lactone (15f). Flash chromatography
with 5:1 tolueneꢀEtOAc produced 2-methyl-2-(2,3,4-tri-
O-acetyl-5-thio-b-D-xylopyranosyl)propanoic
methyl ester 14f in 54% yield; mp 119 8C; [a]D25
L-gluco-
/
acid
ꢃ
/
298
1
(c 0.43, MeOH); H NMR (300 MHz, CDCl3): d 1.13,
1.32 (2s, 6 H, CH3), 1.92, 1.93, 2.0 (3s, 9 H, OAc), 2.65
(m, 1 H, H-5ax), 2.91 (m, 1 H, H-5eq), 3.53 (d, 1 H, J1,-2
10.7 Hz, H-1), 3.7 (s, 3 H, OCH3), 5.0 (m, 2 H, H-2, H-
4), 5.23 (t, 1 H, H-3). Anal. Calcd for C16H24O8S: C,
51.05; H, 6.43. Found: C, 50.96; H, 6.67.
3.6. Use of enoxysilanes: C-glycosyl bond formation
3.6.1. Procedure A. To a solution of bromide 5 and 2.2
equiv of ZnCl2 in CH2Cl2 was added dropwise enol
ether 1243 (2 equiv). One hour later, the mixture was
poured into iced water and extracted with CH2Cl2. The
organic layer was washed (HCl 1 M, brine) and dried
(MgSO4). The residue was purified by flash chromato-
graphy on silica gel. To a suspension of the triacetate 14
in MeOH was added 0.1 equiv of NaOMe and 1 h later
the solution was made neutral with Amberlite† IR-120
(Hꢂ). Filtration and evaporation of the filtrate gave the
product 15.
Compound 15f was obtained: white crystals; quanti-
1
tative yield; mp 200 8C; [a]D25
ꢂ
/
718 (c 0.43, MeOH); H
NMR (300 MHz, Me2SO): d 1.04, 1.18 (2s, 6 H, CH3),
2.6 (m, 1 H, H-5ax), 2.73 (m, 1 H, H-5eq), 3.33 (m, 1 H,
H-3), 3.43 (m, 1 H, H-4), 4.05 (t, 1 H, J 9.5 Hz, H-2),
5.46, 5.59 (2d, 2 H, OH); 13C NMR (60 MHz, Me2SO):
d 18.0 (CH3), 22.0, (CH3), 33.8 (CH2S), 42.8 (C-1), 52.1
(C (CH3)2), 74, 75.7 (C-4, C-3), 83 (C-2), 179.4 (Cꢀ
/
O).
Anal. Calcd for C9H14O4S: C, 49.52; H, 6.46. Found: C,
49.45; H, 6.40.
3.6.1.1. 1-(2,3,4-Tri-O-acetyl-5-thio-b-
syl)propan-2-one (14g). Flash chromatography (3:2
EtOAcꢀpetroleum ether) gave 14g as white crystals;
mp 79 8C; [a]2D1
D-xylopyrano-
/
3.6.2. Procedure B. To a solution of the trichloroaceti-
midate 1344 and 1 equiv of enol ether 12 in CH2Cl2 was
added dropwise 0.1 equiv of trimethylsilyltriflate. One
hour later diisopropylethylamine was added to the
mixture, which was poured into iced water and then
extracted with EtOAc. The organic layer was dried
(MgSO4) and concentrated under diminished pressure.
The residue was purified by flash chromatography on
silica gel and the compound 14 was then deacetylated as
in Procedure A to give 15.
1
ꢃ158 (c 0.5, CH2Cl2); H NMR (200
/
MHz, CDCl3): d 5.1 (t, 1 H, J3,4 9.4 Hz, H-3), 5.02 (m, 1
H, J4,5e 5.2 Hz, H-4), 4.95 (dd, 1 H, J2,3 9.4 Hz, H-2),
3.55 (ddd, 1 H, J1,2 10.2 Hz, H-1), 2.94 (dd, 1 H, J4,5a
10.3 Hz, H-5a), 2.8 (dd, 1 H, J5a,5e 13.3 Hz, H-5e), 2.76
(dd, 1 H, J 4.8 and 17 Hz, CH2), 2.44 (dd, 1 H, J 8.4 Hz,
CH2), 2.13 (s, 3 H, CH3), 1.97 (s, 3 H, OAc), 1.96 (s, 6 H,
OAc). Anal. Calcd for C14H20O7S: C, 50.59; H, 6.07.
Found: C, 50.6; H, 6.16.
3.6.1.2. 2?-(5-Thio-b-
(15a). Flash chromatography with 2:3 EtOAcꢀ
leum ether gave 2?-(2,3,4-tri-O-acetyl-5-thio-b-
pyranosyl)acetophenone 14a in 51% yield; mp 128 8C;
[a]2D1 318 (c 0. 3, CHCl3); 1H NMR (200 MHz,
D
-xylopyranosyl)acetophenone
petro-
-xylo-
3.6.2.1. 4-Cyano-2?-(5-thio-b-
xylopyranosyl)acetophenone (15b). Flash chromatogra-
phy using 9:1 tolueneꢀEtOAc gave 4-Cyano-2?-(2,3,4-
-xylopyranosyl)acetophenone
D-
/
D
/
tri-O-acetyl-5-thio-b-
D
ꢃ
/
(14b) in 33% yield; mp 182 8C; [a]D24
ꢃ388 (c 0.64,
/
1
CHCl3); H NMR (300 MHz, CDCl3): d 1.93 (s, 3 H,
OAc), 2.02 (s, 3 H, OAc), 2.03 (s, 3 H, OAc), 2.76 (m, 1
CDCl3): d 7.93 (d, 2 H, J 7 Hz, Ar), 7.6 (t, 1 H, J 7
Hz, Ar), 7.48 (t, 2 H, J 7 Hz, Ar), 5.17 (t, 1 H, J2,3 9.7

1278
L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ1282
/
H, H-5ax), 2.86 (m, 1 H, H-5eq), 3.08 (m, 2 H, CH2CO),
3.63 (m, 1 H, H-1), 5.11 (t, 1 H, H-3), 4.96 (t, 1 H, J1,2
10.3 Hz, H-2), 4.88 (m, 1 H, H-4), 7.78 (d, 2 H, J 8.4 Hz,
Ph), 8 (d, 2 H, J 8.4 Hz, Ph); 13C NMR (60 MHz,
CDCl3): d 20.1, 20.5, 20.8 (CH3CO), 30.3 (C-5), 39.5,
39.8 (C-1, CH2CO), 72.6, 74, 75.1 (C-2, C-3, C-4), 116.8
(Ph), 117.7 (CN), 128.6 (Ph), 132.7 (Ph), 139 (Ph), 169.7
(CO2), 194.7 (CO). Anal. Calcd for C20H21NO7S: C,
57.27; H, 5.05; N, 3.34. Found: C, 57.04; H, 3.90; N,
3.16.Compound 15b was obtained by flash chromato-
4-Phenyl-1-(5-thio-b-
15d: flash chromatography using 24:1 CH2Cl2ꢀ
72% yield; mp 115 8C; [a]D23
198 (c 0.5, MeOH); H
NMR (300 MHz, Me2SO): d 2.25 (m, 1 H), 2.49 (m, 2
H), 2.72 (m, 4 H), 2.97 (m, 4 H), 3.38 (m, 1 H), 4.9 (d, 1
H, J 3.8 Hz, OH), 5.06 (d, 1 H, J 5 Hz, OH), 5.12 (d, 1
H, J 5 Hz, OH), 7.28 (m, 1 H, Ph). Anal. Calcd for
C15H20O4S: C, 60.78; H, 6.80. Found: C, 60.35; H, 6.87.
D
-xylopyranosyl)-2-butanone
/MeOH;
1
ꢂ
/
3.6.2.4. 4-[[4-(5-Thio-b-
benzonitrile (15e). To a solution of 4-(3-oxobutyl)ben-
zonitrile42 (2.77 g, 16 mmol) in THF (20 mL) at ꢃ
40 8C
D-xylopyranosyl)-3-oxo]butyl]-
graphy using 10:1 CH2Cl2ꢀMeOH then crystallization
/
with 2-propanol; 66% yield; mp 118 8C; [a]D22
ꢂ
/
108 (c
/
1
0.5, MeOH); H NMR (300 MHz, Me2SO): d 2.5 (m, 2
H, H-5, H-5?), 2.94 (m, 2 H, CH2CO), 3.08 (m, 1 H),
3.16 (m, 1 H), 3.39 (m, 1 H), 3.60 (dd, 1 H, J 16.3 Hz, J
3.9 Hz, CH2CO), 4.90 (d, 1 H, J 4 Hz, OH), 5.08 (d, 1 H,
J 4.6 Hz, OH), 5.19 (d, 1 H, J 4.6 Hz, OH), 8,04 (m, 4
H, Ph). Anal. Calcd for C14H15NO4S: C, 57.32; H, 5.15;
N, 4.77. Found: C, 56.77; H, 5.21; N, 4.67.
under Ar atmosphere, was added 1.1 equiv of lithium
diisopropylamide followed by dropwise addition of
trimethylsilyl triflate (14.22 g, 64 mmol) during a period
of 10 min. The reaction was quenched with diisopropy-
lethylamine (10 mL) and poured into NaHCO3 solution
(50 mL) with ice. The mixture was extracted with
pentane and the organic layer was concentrated under
diminished pressure. The residue was purified by flash
chromatography on silica gel with 5:1:0.01 pentaneꢀ
/
3.6.2.2. 4-Phenyl-1-(5-thio-b-
buten-2-one (15c). Flash chromatography using 9:1
tolueneꢀEtOAc yielded 4-phenyl-1-(2,3,4-tri-O-acetyl-
5-thio-b- -xylopyranosyl)-(E)-3-buten-2-one (14c)
(29%); mp 156 8C; [a]2D3 198 (c 0.6, CHCl3); 1H
NMR (300 MHz, CDCl3): d 1.93, 1.95, 1.98 (3s, 9 H,
OAc), 2.73, (m, 2 H, H-5eq, CH2CO), 2.96 (m, 1 H,
CH2CO), 2.98 (m, 1 H, H-5ax), 3.71 (m, 1 H, H-1), 4.86
(m, 1 H, H-3), 4.92 (t, 1 H, J 10.2 Hz, H-2), 5.1 (t, 1 H, J
D
-xylopyranosyl)-(E)-3-
etherꢀtriethylamine and the product, a colorless liquid
/
(yield 34%) was used immediately for the synthesis of
14e.
Starting from 4-[3-[(trimethylsilyl)oxy]-3-butenyl]ben-
/
D
ꢂ
/
zonitrile, flash chromatography using 5:2 cyclohexaneꢀ
EtOAc yielded 4-[[4-(2,3,4-tri-O-acetyl-5-thio-b- -xylo-
pyranosyl)-3-oxo]butyl]benzonitrile 14e (11%); mp
170 8C; [a]2D9 128 (c 0.15, CHCl3); 1H NMR (300
/
D
ꢃ
/
MHz, Me2SO): d 1.93, 1.94, 1.98 (3s, 9 H, OAc), 2.46
(m, 1 H, CH2CO), 2.72 (m, 2 H, H-5eq, CH2CO), 2.83
9.5 Hz, H-3), 6.94 (d, 1 H, J 15 Hz, CH ꢀ
5 H, Ph), 7.60 (d, 1 H, CHꢀCH Ph). HRMS: Calcd for
C21H24O7NaS [MꢂNa], 443.1140; Found: 443.1140.
Compound 15c was obtained by flash chromatogra-
phy using 9:1 CH2Cl2ꢀMeOH; 80% yield; mp 117 8C;
[a]D19:50 278 (c 0.6, MeOH); 1H NMR (300 MHz,
/
CHPh), 7.3 (m,
/
(s, 4 H, CH2ꢁ/CH2), 2.95 (m, 1 H, H-5ax), 3.60 (m, 1 H,
/
H-1), 4.82 (t, 1 H, J1,2 9.6 Hz, H-2), 4.88 (m, 1 H, H-4),
5.07 (t, 1 H, J 9.6 Hz, H-3), 7.42 (d, 2 H, J 8.4 Hz, Ar),
7.73 (d, 2 H, J 8.4 Hz, Ar). Anal. Calcd for
C22H25NO7S: C, 59.05; H, 5.63. Found: C, 59.15; H,
5.70.
/
ꢂ
/
Me2SO): d 2.45 (m, 2 H), 2.57 (m, 1 H), 2.95 (m, 1 H),
3.06 (2 H), 3.12 (m, 1 H), 3.40 (m, 1 H), 4.95 (broad s, 1
H, OH), 5.08 (broad s,1 H, OH), 5.17 (broad s, 1 H,
OH), 6.92 (d, 1 H, J 16.2 Hz), 7.43 (m, 3 H), 7.60 (d, 1
H, J 16.2 Hz), 7.73 (m, 2 H, Ph). Anal. Calcd for
C15H18O4S; 0.16 H2O: C, 60.612; H, 6.21. Found: C,
60.39; H, 6.20.
4-[[4-(5-Thio-b-
nitrile 15e: Flash chromatography using 6:4:0.01
MeCNꢀwaterꢀtrifluoroacetic acid; yield 77%; mp
153 8C; [a]2D4 128 (c 0.22, MeOH); 1H NMR (300
D-xylopyranosyl)-3-oxo]butyl]benzo-
/
/
ꢂ
/
MHz, Me2SO): d 2.26 (m, 1 H), 2.49 (m, 1 H), 2.90 (m, 8
H), 3.37 (m, 1 H), 4.90 (d, 1 H, J 4.2 Hz, OH), 5.07 (d, 1
H, J 4.9 Hz, OH), 5.14 (d, 1 H, J 4.9 Hz, OH), 7.42 (d, 2
H, J 8.4 Hz, Ar), 7.73 (d, 2 H, J 8.4 Hz, Ar). Anal.
Calcd for C16H19NO4S; 0.37 H2O: C, 58.58; H, 6.06; N,
4.27. Found: C, 58.46; H, 5.92; N, 4.18.
3.6.2.3. 4-Phenyl-1-(5-thio-b-
butanone (15d). Flash chromatography using 4:1
methylcyclohexaneꢀEtOAc yielded 4-phenyl-1-(2,3,4-
tri-O-acetyl-5-thio-b- -xylopyranosyl)-2-butanone 14d
(13%); mp 124 8C; [a]2D5 218 (c 0.5, MeOH); 1H
D-xylopyranosyl)-2-
/
D
ꢂ
/
3.6.2.5. 2-[5-Thio-b-D-xylopyranosyl)-1-hydroxy-
NMR (300 MHz, Me2SO): d 1.92, 1.94, 1.97 (3s, 9 H,
OAc), 2.43 (m, 1 H, CH2CO), 2.67 (m, 1 H, CH2CO),
ethyl]benzonitrile (17b). To a solution of compound 14b
(510 mg, 1.22 mmol) in CH2Cl2 (25 mL) and MeOH (5
mL) was added NaBH4 (100 mg, 2.6 mmol) under an
inert atmosphere. The mixture was hydrolyzed 30 min
later on iced water and extracted with CH2Cl2. The
organic layer was washed with water, dried and
evaporated under diminished pressure. The residue
2.76 (s, 4 H, CH2ꢁ
/
CH2), 2.77 (m, 1 H, H-5eq), 2.95 (m,
1 H, H-5ax), 3.6 (m, 1 H, H-1), 4.82 (t, 1 H, J 9.6 Hz, H-
2), 4.86 (m, 1 H, H-4), 5.07 (t, 1 H, J 9.6 Hz, H-3), 7.22
(m, 5 H, Ph). HRMS: Calcd for C21H26O7NaS [Mꢂ
/
Na],
445.1297; Found: 445.1289.

L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ
/
1282
1279
gave [2-(2,3,4-tri-O-acetyl-5-thio-b-
D
-xylopyranosyl)-1-
(300 MHz, Me2SO): d 1.53 (m, 1 H, CH2CH2Ph), 2.26
(m, 1 H, CH2CH2Ph), 2.45 (m, 1 H, H-5ax), 2.56 (m, 1
H, H-5eq), 2.67 (m, 1 H, CH2Ph), 2.85 (m, 2 H, CH2Ph,
H-2), 3.12 (m, 2 H, H-3,4), 3.38 (m, 1 H, H-1), 4.86 (d, 1
H, J 4.2 Hz, OH), 5.04 (m, 2 H, OH), 7.41 (d, 2 H, J 8.2
Hz, Ph) 7.74 (d, 2 H, J 8.2 Hz, Ph). Anal. Calcd for
C14H17NO3S: C, 60.19; H, 6.13; N, 5.01. Found: C,
59.88; H, 6.14; N, 4.81.
hydroxyethyl]benzonitrile (500 mg, 97.5%); 1H NMR
(300 MHz, CDCl3): d 2.01, (s, 9 H, OAc), 2.03, (m, 2.5
H), 2.33 (d, 0.5 H, J 4.5 Hz OH), 2.6 (m, 1.5 H) 2.9 (m, 1
H), 3.26 (m, 0.5 H), 5.04 (m, 4 H), 7.47 (m, 2 H, Ph),
7.65 (m, 2 H, Ph). To this product (380 mg, 0.9 mmol) in
MeOH (20 mL) was added a NaMeO solution (55 mL,
18% in MeOH). After stirring this mixture one for 1 h,
the mixture was neutralized with Amberlite† IR-120
(Hꢂ resin). After filtration, the residue was concen-
trated under diminished pressure and purified by flash
3.6.2.7. Phenyl
(5-thio-a,b-D-xylopyranosyl)methyl
sulfone (18). To a stirred solution of diethyl phenylsul-
fonylmethyl phosphonate (14 g, 47.9 mmol) in THF (10
mL) under N2 cooled at 0 8C was added dropwise a
solution of sodium bis(trimethylsilyl)amide (96 mL, 96
mmol, 1 M in THF). The solution was stirred for 30
min, and then concentrated under vacuum. A solution
chromatography on silica gel with 9:1 CH2Cl2ꢀ
and by lyophilisation to give 17b (260 mg; 97%); mp
80 8C; [a]2D2 9.28 (c 0.24, Me2SO); 1H NMR (300 MHz,
/
MeOH
ꢃ
/
Me2SO): d 1.28 (m, 0.5 H, CH2Ph), 1.60 (m, 0.5 H,
CH2CPh), 2.40 (m, 3.5 H, H-1, CH2CPh, H-5), 2.85 (m,
1.5 H, H-3,2), 3.12 (m, 1 H, H-2), 3.40 (m, 1 H, H-4),
4.86 (m, 1 H, OH), 5.07 (m, 2 H, OH), 5.12 (m, 2 H, OH,
CHPh), 5.55 (d, 0.5 H, J 4.5 Hz, OH), 5.62 (d, 0.5 H, J
4.5 Hz OH), 7.54 (m, 2 H, Ph), 7.82 (m, 2 H, Ph). Anal.
Calcd for C14H17NO7S: C, 55.61; H, 5.93; N, 4.63.
Found: C, 55.27; H, 5.85; N, 4.56.
of 5-thio-D-xylopyranose (4 g, 24.07 mmol) in dry
pyridine (50 mL) was added to the white crystals. The
solution was then stirred under N2 at 80 8C for 25 min
and then concentrated in vacuo. Flash chromatographic
purification (9:1 CH2Cl2ꢀCH3OH) on silica gel yielded
/
2.2 g (30%) of 18 as a yellow oil (1:1 mixture of a and b
1
anomers). H NMR (300 MHz, Me2SO): d 2.39ꢀ
(m, 2 H, H-5), 2.82ꢀ2.94 (m, 1 H, H-1b,3b), 3.01ꢀ
(m, 1 H, H-2b,3a), 3.12ꢀ
3.40 (m, 1.5 H, H-4, CH2SO2b), 3.52ꢀ
/
2.48
3.6.2.6. [2-(5-Thio-b-
nitrile (16b). A solution of [2-(2,3,4-tri-O-acetyl-5-thio-
b- -xylopyranosyl)-1-hydroxyethyl]benzonitrile (2 g,
D-xylopyranosyl)ethyl]benzo-
/
/3.09
/
3.18 (m, 0.5 H, H-1a), 3.32ꢀ
/
D
/
3.58 (m, 1 H, H-
4.75 mmol), dimethylaminopyridine (6.08 g, 50 mmol),
phenyl chlorothionocarbonate (2 mL, 15 mmol) in
MeCN (60 mL) was stirred under inert atmosphere for
2 h. The mixture was then neutralized (NaHCO3 5%)
and concentrated under diminished pressure. The resi-
due was dissolved in CH2Cl2, washed with water, dried
2a, CH2SO2a), 3.68 (dd, 0.5 H, J 9.0 and 15.0 Hz,
CH2SO2a), 3.82 (dd, 0.5 H, J 2.0 and 15.0 Hz,
CH2SO2b), 4.89 (d, 0.5 H, J 4.5 Hz, OH), 4.95 (d, 0.5
H, J 4.5 Hz, OHa), 5.01 (d, 0.5 H, J 4.5 Hz, OHb), 5.10
(d, 0.5 H, J 4.5 Hz, OHa) 5.31 (d, 0.5 H, J 5.5 Hz,
OHb), 5.33 (d, O.5 H, J 5.5 Hz, OHa), 7.61ꢀ
/7.67 (m, 2
and evaporated. [2-(2,3,4-Tri-O-acetyl-5-thio-b-
D-xylo-
H, Ar meta), 7.71ꢀ7.75 (m, 1 H, Ar para), 7.89ꢀ
/
/
7.92 (m,
pyranosyl)-1-(phenylthiocarbonate)oxoethyl)benzoni-
trile was obtained (2.38 g, 90%) by flash chromato-
2 H, Ar ortho).
graphy on silicagel with 3:2 methylcyclohexaneꢀ
/
EtOAc.
3.6.2.8. Phenyl
sulfone (18a). (2,3,4-Tri-O-acetyl-5-thio-a-
nosyl)methylphenyl sulfone 19a (0.4 g, 0.93 mmol) was
deacetylated using the procedure described for [2-(2,3,4-
tri-O-acetyl-5-thio-b-
with sodium methoxide. The compound was obtained as
a white powder (0.277 g, 98% yield); mp 50 8C; [a]D27
958 (c 0.40, CH3OH); H NMR (300 MHz, Me2SO): d
2.43 (m, 2 H, H-5), 3.05 (m, 1 H, H-3), 3.16 (m, 1 H, H-
1), 3.36 (m, 1 H, H-4), 3.52ꢀ3.59 (m, 2 H, H-2,
(5-thio-a-
D
-xylopyranosyl)methyl
-xylopyra-
A solution of [2-(2,3,4-tri-O-acetyl-5-thio-b- -xylopyr-
D
D
anosyl)-1-(phenylthiocarbonate)oxoethyl]benzonitrile
(2.3 g, 4.12 mmol), azobisisobutyronitrile (138 mg, 0.84
mmol), tributyltin hydride (1.7 mL, 6.43 mmol) in
toluene (60 mL) was boiled at 110 8C for 45 min. The
mixture was evaporated and subjected to flash chroma-
D-xylopyranosyl)ethyl]benzonitrile
ꢂ
/
1
tography on silica gel with 6:1 tolueneꢀ
/
EtOAc. [2-
(2,3,4-Tri-O-acetyl-5-thio-b- -xylopyranosyl)ethyl]ben-
D
zonitrile was obtained (1.37 g, 82%); 1H NMR (300
MHz, Me2SO): d 1.51 (m, 1 H, CH2CH2Ph), 1.91 (m, 1
H, CH2CH2Ph), 1.95, 1.97, 2.0 (3s, 9 H, OAc), 2.65 (m,
1 H, CH2Ph), 2.83 (m, 3 H, CH2Ph, H-5), 3.14 (m, 1 H,
H-1), 4.90 (m, 2 H, H-2,4), 5.05 (t, 1 H, H-3), 7.40 (d, 2
H, Ph), 7.75 (d, 2 H, Ph). To a suspension of this
product (1.53 g, 3.78 mmol) in MeOH (60 mL) was
added 18% MeOH solution of NaOMe (180 mL). One
hour later the mixture was neutralized with Amberlite†
IR-120 (Hꢂ) resin, filtered and evaporated. The residue
/
CH2SO2), 3.68 (dd, 1 H, J 9.0 and 15.0 Hz, CH2SO2),
4.95 (d, 1 H, J 4.5 Hz, OH), 5.10 (d, 1 H, J 5.5 Hz, OH),
5.31(d, 1 H, J 5 Hz, OH), 7.64 (t, 2 H, J 7 Hz, Ar meta),
7.70ꢀ7.76 (m, 1 H, Ar para), 7.91 (d, 2 H, J 7 Hz, Ar
/
ortho). Anal. Calcd For C12H16O5S2; 0.39 H2O: C,
46.28; H, 5.43, Found: C, 45.86; H, 5.17.
3.6.2.9. Phenyl
sulfone (18b). (2,3,4-Tri-O-acetyl-5-thio-b-
nosyl)methyl phenyl sulfone (19b, 0.43 g, 1 mmol) was
(5-thio-b-
D
-xylopyranosyl)methyl
D-xylopyra-
was crystallized in MeOHꢀ
/
ether to give 16b (0.5 g,
50%); mp 144 8C; [a]2D3 248 (c 0.41, MeOH); 1H NMR
ꢃ
/
deacetylated with NaOMe using the procedure de-

1280
L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ1282
/
scribed for [2-(2,3,4-tri-O-acetyl-5-thio-b-
syl)ethyl]benzonitrile. The compound was obtained as a
white powder (0.26 g, 65% yield); mp 163 8C; [a]D28
48
(c 0.42, CH3OH); 1H NMR (300 MHz, Me2SO): d 2.37
(dd, 1 H, J 10.5 and 13.0 Hz, H-5), 2.82ꢀ2.94 (m, 2 H,
H-1,3), 3.05 (m, 1 H, H-2), 3.34ꢀ3.37 (m, 2 H, H-4,
CH2SO2), 3.82 (dd, 1 H, J 2.0 and 15.0 Hz, CH2SO2),
4.89 (d, 1 H, J 4.5 Hz, OH), 5.01 (d, 1 H, J 4.5 Hz, OH),
5.31 (d, 1 H, J 5.5 Hz, OH), 7.62 (t, 2 H, J 7.0 Hz, Ar
meta), 7.75 (t, 1 H, J 7.0 Hz, Ar para), 7.91 (d, 2 H, J
7.0 Hz, Ar ortho). Anal. Calcd For C12H16O5S2: C,
47.35; H, 5.30. Found: C, 46.94; H, 5.14.
D
-xylopyrano-
CH2SO2, H-4), 3.88ꢀ3.96 (m, 1 H, CH2SO2), 4.95 (d,
1 H, J 5 Hz, OH), 5.12 (d, 1 H, J 5 Hz, OH), 5.37 (d, 1
H, J 5 Hz, OH), 8.14 (s, 4 H, Ar).
/
ꢂ
/
/
3.6.2.12. 4-([5-Thio-a-
sulfonyl]benzonitrile (20a). 4-[(2,3,4-Tri-O-acetyl-5-thio-
a- -xylopyranosyl)methyl sulfonyl]benzonitrile (21a,
0.80 g, 1.76 mmol) was deacetylated using the usual
procedure with MeOHꢀNH3 for 2 h. The product was
obtained as a white powder (0.56 g, 97% yield); mp
D-xylopyranosyl)methyl
/
D
/
1
170 8C; [a]2D3
MHz, Me2SO): d 2.32ꢀ
J 8.5 and 4.5 Hz, H-3), 3.12ꢀ
ꢂ
/
1248 (c 0.26, CH3OH); H NMR (300
2.45 (m, 2 H, H-5), 3.02 (td, 1 H,
3.16 (m, 1 H, H-1), 3.34ꢀ
/
/
/
3.6.2.10. (2,3,4-Tri-O-acetyl-5-thio-a-
xylopyranosyl)methyl phenyl sulfone (19a and 19b).
Phenyl (5-thio- -xylopyranosyl)methyl sulfone (18,
1.44 g, 4.73 mmol) was acetylated conventionally and
after flash chromatographic purification on silica gel (6:4
and
b-
D
-
3.38 (m, 1 H, H-2), 3.53 (ddd, 1 H, J 8.5 and 4.5 and 5.5
Hz, H-4), 3.60 (dd, 1 H, J 15.0 and 2.5 Hz, CH2SO2),
3.93 (dd, 1 H, J 15.0 and 10.0 Hz, CH2SO2), 4.96 (d, 1
H, J 4.5 Hz, OH); 5.12 (d, 1 H, J 4.5 Hz, OH); 5.39 (d, 1
H, J 5.5 Hz, OH); 8.14 (s, 4 H, Ar). Anal. Calcd For
C13H15NO5S2; 0.5 H2O: C, 46.09; H, 4.72; N, 4.13.
Found: C, 45.73; H, 4.70; N, 3.98.
D
tolueneꢀether), afforded 0.415 g of compound 19b as
/
white powder (28% yield); mp 50 8C; [a]D28
CHCl3); H NMR (300 MHz, Me2SO): d 1.93 (s, 3 H,
Ac), 1.94 (s, 3 H, Ac), 1.96 (s, 3 H, Ac), 2.69 (dd, 1 H, J
4.5 and 13.0 Hz, H-5), 2.95 (dd, 1 H, J 11 and 13.5 Hz,
ꢃ58 (c 0.42,
/
1
3.6.2.13. 4-[(5-Thio-b-
sulfonyl]benzonitrile (20b). 4-[(2,3,4-Tri-O-acetyl-5-thio-
b- -xylopyranosyl)methyl sulfonyl]benzonitrile (21b,
0.15 g, 0.33 mmol) was deacetylated with MeOHꢀNH3
D-xylopyranosyl)methyl
H-5?), 3.34 (m, 1 H, H-1), 3.40ꢀ/3.60 (m, 2 H, CH2SO2),
D
4.77ꢀ4.84 (m, 1 H, H-4), 4.82 (t, 1 H, J 9.5 Hz, H-2),
/
/
5.10 (t, 1 H, J 9.5 Hz, H-3), 7.64 (t, 2 H, J 7.0 Hz, Ar
meta), 7.77 (m, 1 H, Ar para), 7.95 (d, 2 H, J 7.0 Hz, Ar
for 2 h. The product was obtained as a white powder
(0.1 g, 93% yield); mp 180 8C; [a]D23
ꢂ
/
158 (c 0.43,
2.49
2.94 (m, 2 H, H-1,3), 3.05 (td, 1 H,
J 9.5 and 5.5 Hz, H-2), 2.29ꢀ3.35 (m, 1 H, H-4), 3.52
1
ortho); HRMS: Calcd for C18H22O8NaS2 [Mꢂ
453.0654; Found: 453.0642, and 0.376 g of 19a isomer
as white powder (25% yield); mp 145 8C; [a]D27
928 (c
/Na],
CH3OH); H NMR (300 MHz, Me2SO): d 2.41ꢀ
/
(m, 2 H, H-5), 2.83ꢀ
/
ꢂ
/
/
0.38, CHCl3); 1H NMR (300 MHz, Me2SO): d 1.90 (s, 3
H, Ac), 1.96, (s, 3 H, Ac), 1.97 (s, 3 H, Ac), 2.63 (dd, 1
H, J 4.5 and 13.5 Hz, H-5), 2.96 (dd, 1 H, J 11 and 13.5
Hz, H-5?), 3.32 (m, 1 H, H-1), 3.50 (dd, 1 H, J 2.0 and
15.0 Hz, CH2SO2), 4.23 (dd, 1 H, J 9.0 and 15.0 Hz,
CH2SO2), 4.83 (ddd, 1 H, J 4.5, 10.0 and 11.0 Hz, H-4),
4.85 (dd, 1 H, J 5.0 and 10.0 Hz, H-2), 5.03 (t, 1 H, J
10.0 Hz, H-3), 7.66 (t, 2 H, J 7.5 Hz, Ar meta), 7.76 (t, 1
H, J 7.5 Hz, Ar para), 7.93 (d, 2 H, J 7.5 Hz, Ar ortho).
(dd, 1 H, J 9.5 and 15.0 Hz, CH2SO2), 3.86 (dd, 1 H, J
2.0 and 15.0 Hz, CH2SO2), 4.95 (d, 1 H, J 5.5 Hz, OH),
5.05 (d, 1 H, J 5.5 Hz, OH), 5.37 (d, 1 H, J 5.5 Hz, OH),
8.14(s, 4 H, Ar). Anal. Calcd For C13H15NO5S2; 0.5
H2O: C, 46.09; H, 4.72; N, 4.13. Found: C, 45.70; H,
4.79; N, 4.07.
3.6.2.14. 4-([2,3,4-Tri-O-acetyl-5-thio-a- and b-
xylopyranosyl)methyl sulfonyl]benzonitrile (21a and
21b). 4-([5-Thio- -xylopyranosyl)methyl sulfony]benzo-
D-
HRMS: Calcd for C18H22O8NaS2 [MꢂNa], 453.0654;
/
D
Found: 453.0642.
nitrile (20) (4.08, 12.4 mmol) was for acetylated and,
conventionally after flash chromatographic separation
3.6.2.11. 4-((5-Thio-D-xylopyranosyl)methyl
on silica gel (6:4 tolueneꢀ
21a anomer as a white powder (32% yield); mp 117 8C;
[a]2D3 1228 (c 0.40, CH3OH); 1H NMR (300 MHz,
Me2SO): d 1.96 (s, 3 H, Ac), 1.97 (s, 3 H, Ac), 1.98 (s, 3
H, Ac), 2.59 (dd, 1 H, J 4.5 and 13.5 Hz, H-5), 2.86 (dd,
/
ether), afforded 1.28 g of the
sulfonyl)benzonitrile (20). To a stirred solution of diethyl
methyl-(4-cyanophenyl)sulfonyl phosphonate (23.9 g, 78
mmol) in anhydrous pyridine (50 mL) under N2 and
cooled at 5 8C was added NaH (3 g, 125 mmol). The
mixture, which became pale yellow, was stirred for 20
ꢂ
/
1 H, J 11.0 and 13.5 Hz, H-5), 3.37ꢀ3.41 (m, 1 H, H-1),
/
min and then 5-thio-
D
-xylopyranose (2.5 g, 15 mmol)
3.63 (dd, 1 H, J 2.5 and 15.5 Hz, CH2SO2), 4.45 (dd, 1
H, J 10.0 and 15.5 Hz, CH2SO2), 4.83 (ddd, 1 H, J 10.0,
11.0 and 4.5 Hz, H-4), 4.94 (dd, 1 H, J 5.0 and 10.0 Hz,
H-2), 5.06 (t, 1 H, J 10.0 Hz, H-3), 8.16 (s, 4 H, Ar).
Anal. Calcd For C19H21NO8S2: C, 50.10; H, 4.65; N,
3.07. Found: C, 49.77; H, 4.63; N, 3.20. The anomer 21b
was obtained as a white powder (0.41 g, 11% yield); mp
was added. The mixture was stirred at rt under N2 at
80 8C for 2 h and then concentrated under vacuum.
The crude product was purified by flash chromato-
graphy (9:1 CH2Cl2ꢀ
yellow powder as a 7:3 mixture of a and b anomers. H
NMR (300 MHz, Me2SO): d 2.38ꢀ2.44, (m, 2 H, H-5),
3.01ꢀ3.16 (m, 3 H, H-1,2,3), 3.30ꢀ3.64 (m, 2 H,
/CH3OH) to yield 1.55 g (31%) of
1
/
/
/
153 8C; [a]2D3
ꢃ
18 (c 0.60, CHCl3); 1H NMR (300 MHz,
/

L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ
/
1282
1281
Me2SO): d 1.98 (s, 3 H, Ac), 1.99 (s, 3 H, Ac), 2.01 (s, 3
H, Ac), 2.68 (dd, 1 H, J 4.5 and 13.0 Hz, H-5), 2.92 (dd,
and the solvent removed under diminished pressure.
Purification by flash chromatography 9:1 CH2Cl2ꢀ
CH3OH yielded 2.22 g (29%) of brown powder as a
/
1 H, J 11.0 and 13.0 Hz, H-5), 3.52ꢀ/3.69 (m, 3 H, H-1,
1
CH2SO2), 4.77ꢀ4.85 (m, 2 H, H-2,4), 5.10 (t, 1 H, J 9.5
/
1:1 mixture of a and b anomers. H NMR (300 MHz,
Hz, H-3), 8.16 (s, 4 H, Ar). Anal. Calcd For
C19H21NO8S2: C, 50.10; H, 4.65; N, 3.07. Found: C,
50.02; H, 4.68; N, 2.96.
Me2SO): d 2.18 (t, 0.5 H, J 15.0 Hz, H-5b), 2.38ꢀ
/2.66
(m, 3 H, CH2, H-5), 2.86 (dd, 0.5 H, J 3.5 and 15.0 Hz,
H-5a), 2.96ꢀ3.10 (m, 1.5 H, H-2b,3b,4b), 3.14 (m, 0.5 H,
H-3a), 3.25 (m, 0.5 H, H-4a), 3.25ꢀ3.47 (m, 1 H, H-1),
/
/
3.6.2.15. Ethyl (2,3,4-tri-O-acetyl-
osyl)acetate (22). 5-Thio-D-xylopyranose (9.1 g, 54.76
D-thioxylopyran-
3.62 (m, 0.5 H, H-2a), 4.92 (d, 0.5 H, J 4 Hz, OH), 4.94
(d, 0.5 H, J 3.5 Hz, OH), 5.08 (d, 0.5 H, J 4.5 Hz, OH),
5.20 (d, 0.5 H, J 5 Hz, OH), 5.21 (d, 0.5 H, J 4.5 Hz,
OH), 5.25 (d, 0.5 H, J 5 Hz, OH), 7.77 (s, 4 H, Ar),
10.41 (s, 0.5 H, NHCO), 10.50 (s, 0.5 H, NHCO).
mmol) and (ethoxycarbamylmethylene) triphenyl phos-
phorane (30.5 g, 87.55 mmol) were dissolved in pyridine
(60 mL). The reaction mixture was then stirred at 90 8C
for 10 h. The solvent was then removed under vacuum
and the crude mixture purified by flash chromatography
3.6.2.17. 4-[(5-Thio-a-
benzonitrile (23a). The same procedure as those used for
23b yielded 0.3 g of 23a (93.5% yield); mp 90 8C; [a]D25
2218 (c 0.43, CH3OH); 1H NMR (300 MHz, Me2SO): d
2.53ꢀ2.66 (m, 3 H, CH2, H-5), 2.86 (dd, 1 H, J 3.5 and
D-xylopyranosyl)acetamido]-
(95:5 CH2Cl2ꢀCH3OH) to yield ethyl (5-thio-D-xylopyr-
/
anosyl)acetate as a brown oil (4.64 g, 36%). Recrystalli-
zation in ether gave a yellow powder (2.74 g, 21%); mp
ꢂ
/
1
75 8C; H NMR (300 MHz, Me2SO): d 1.18 (m, 3 H,
/
CH3), 2.10 (dd, 0.5 H, J 9 and 15 Hz, CH2CO), 2.43 (dd,
0.5 H, J 11 and 15 Hz, CH2CO), 2.49 (s, 1 H, CH2CO),
2.90 (m, 2 H, H-5), 3.13 (m, 2 H, H-3,4), 3.39 (m, 1 H,
H-1), 3.57 (m, 1 H, H-2), 4.08 (m, 2 H, OCH2), 4.84 (d, 1
H, J 3 Hz, OH), 5.02 (d, 1 H, J 5 Hz, OH,), 5.11 (d, 0.5
H, J 5.5 Hz, OH), 5.15 (d, 0.5 H, J 5 Hz, OH). Ethyl (5-
15.0 Hz, H-5?), 3.14 (m, 1 H, H-3), 3.25 (m, 1 H, H-4),
3.43 (m, 1 H, H-1), 3.62 (m, 1 H, H-2), 4.92 (d, 1 H, J
4.0 Hz, OH), 5.21 (d, 1 H, J 4.5 Hz, OH), 5.25 (d, 1 H, J
5.0 Hz, OH), 7.77 (s, 4 H, Ar), 10.5 (s, 1 H, NHCO).
Anal. Calcd For C14H16N2O4S; 0.44 H2O: C, 53.16; H,
5.38; N, 8.86. Found: C, 53.22;H, 5.35; N, 8.69.
thio-
D-xylopyranosyl)acetate (10.5 g, 44.44 mmol) was
dissolved in pyridineꢀ
/
CH2Cl2 (60 mL, 2:1) and cooled
3.6.2.18. 4-[(5-Thio-b-
xylopyranosyl)acetamido]benzonitrile (23b). 4-[(2,3,4-Tri-
O-acetyl-5-thio-b- -xylopyranosyl)acetamido]benzoni-
trile (24b, 0.77 g, 1.77 mmol) was dissolved in MeOH (30
mL) and a saturated solution of NH3 in MeOH (6 mL)
was added. The mixture was then stirred at rt for 3 h, the
solvent removed under diminished pressure, and the
D-
in an ice bath, and then Ac2O (30 mL) was added
dropwise. The mixture was stirred overnight at rt,
cooled in an ice bath, quenched with 1 M aq HCl (100
mL), and extracted with ether (500 mL). The organic
layer was washed with 1 M HCl (100 mL), saturated
D
NaHCO3 (2ꢄ100 mL), water (100 mL) and dried
/
(MgSO4). The solvent was removed under diminished
pressure to yield 15.4 g of a and b anomers (1:1) as a
yellow oil (96% yield). H NMR (300 MHz, Me2SO): d
crude product lyophilised from water to yield 0.6 g of
1
25b (97%); mp 162 8C; [a]D22
NMR (300 MHz, Me2SO): d 2.18 (t, 1 H, J 15.0 Hz, H-
ꢂ
/
208 (c 1.02, CH3OH); H
1
1.18 (2t, 3 H, J 7.0 Hz, CH3), 1.95ꢀ
COCH3), 2.22 (s, 2 H, CH2CO2Et), 2.58ꢀ
H-5), 3.35 (m, 0.5 H, H-2), 3.53 (m, 0.5 H, H-1b), 4.10
(m, 2 H, OCH2CH3), 4.83ꢀ4.91 (m, 2.5 H, H-2b,4), 5.03
(dd, 0.5 H, J 5.0 and 10.0 Hz, H-2a), 5.11 (t, 0.5 H, J
10.0 Hz, H-3b), 5.14 (t, 0.5 H, J 10.0 Hz, H-3a). Anal.
Calcd For C15H22O8S: C, 49.71; H, 6.12. Found: C,
49.86; H, 6.22.
/
1.99 (6s, 9 H,
5), 2.38ꢀ2.50 (m, 3 H, CH2, H-5?), 2.96ꢀ3.11 (m, 3 H,
/
/
/3.04 (2m, 2 H,
H-2,3,4), 3.38 (m, 1 H, H-1), 4.94 (d, 1 H, J 3.5 Hz,
OH), 5.08 (d, 1 H, J 4.5 Hz, OH), 5.20 (d, 1 H, J 5.0 Hz,
OH), 7.77 (s, 4 H, Ar), 10.41 (s, 1 H, NHCO). Anal.
Calcd For C14H16N2O4 S; 0.48 H2O: C, 53.04; H, 5.39;
N, 8.84. Found: C, 53.31; H, 5.29; N, 8.76.
/
3.6.2.19. 4-[(2,3,4-Tri-O-acetyl-5-thio-a- and b-
xylopyranosyl)acetamido]benzonitrile (24a and 24b). 4-
[(5-Thio- -xylopyranosyl)acetamido]benzonitrile 23 (2
g, 6.49 mmol) was dissolved in pyridineꢀAc2O (60/20
D-
3.6.2.16. 4-[(5-Thio-D-xylopyranosyl)acetamido]-
benzonitrile (23). 4 Aminobenzonitrile (14.5 g, 122.74
mmol) was dissolved in dimethoxyethane (DME, 50
D
/
mL) at 0 8C and then stirred overnight at rt. After
conventional workup (see compound 22) the crude
mL) and molecular sieves 13ꢄ was added. Then NaH
/
(7.4 g, 308.33 mmol) was added slowly. To the reaction
mixture which became yellow then green and then
brown in 15 min, DME (50 mL) was added. After 30
min of stirring at rt compound 22 (8.90 g, 24.56 mmol)
in DME (10 mL) was added. The reaction was complete
in 10 min. The reaction mixture was poured on ice (200
product was flash chromatographed using 1:1 tolueneꢀ
/
ether as solvent to yield 1.18 g of the b anomer (42%
1
yield); mp 201 8C; [a]D25
ꢂ98 (c 0.51, MeOH); H NMR
/
(300 MHz, Me2SO): d 1.91 (s, 3 H, Ac), 1.95 (s, 3 H,
Ac), 1.98 (s, 3 H, Ac), 2.33 (dd, 1 H, J 15 and 19 Hz,
CH2), 2.70 (dd, 1 H, J 15 and 5 Hz, CH2), 2.75 (dd, 1 H,
J 13 and 4.5 Hz, H-5), 2.99 (dd, 1 H, J 13 and 11 Hz, H-
mL) extracted with EtOAc (3ꢄ300 mL), dried (MgSO4)
/

1282
L. Mignon et al. / Carbohydrate Research 338 (2003) 1271ꢀ1282
/
19. Whistler, R. L.; Van Es, T. J. Org. Chem. 1963, 28, 2303ꢀ
2304.
20. (a) Yuasa, H.; Tamura, J. I.; Hashimoto, H. J. Chem. Soc.,
/
5?), 2.61 (sextet, 1 H, J 9.5, 9 and 5 Hz, H-1), 4.90 (m, 1
H, H-4), 4.91 (t, 1 H, J 9.5 Hz, H-2), 5.12 (t, 1 H, J 9.5
Hz, H-3), 7.77 (s, 4 H, Ar), 10.41 (s, 1 H, NHCO). Anal.
Perkin Trans. 1 1990, 2763ꢀ
(b) McAllister, G. D.; Taylor, R. J. K. Tetrahedron Lett.
2001, 1197ꢀ1200.
21. Gallagher, M. J.; Harvey, S.; Raston, C. L.; Sue, R. E. J.
Chem. Soc., Chem. Commun. 1988, 289ꢀ290.
22. BeMiller, J. N.; Yadav, M. P.; Kalabokis, V. N.; Myers,
R. W. Carbohydr. Res. 1990, 200, 111ꢀ126.
23. Coxon, B.; Fletcher, H. G., Jr. J. Am. Chem. Soc. 1964,
86, 922ꢀ925.
24. Allevi, P.; Anastasia, M.; Ciuffreda, P.; Frecchi, A.; Scala,
A. J. Chem. Soc., Perkin Trans. 1 1989, 1275ꢀ1280.
25. Kobayashi, M.; Shimadate, T. Chem. Pharm. Bull. 1986,
34, 4069ꢀ4074.
26. Cai, M. S.; Qiu, D. X. Carbohydr. Res. 1989, 191, 125ꢀ
/2769;
Calcd for C20H22N2O7S×
/
0.11 H2O: C, 54.85; H, 5.15; N,
6.40. Found: C, 54.73; H, 5.01; N, 6.24. The a anomer
/
(0.57 g, 25% yield) had mp 195 8C; [a]D22
ꢂ1508 (c 0.31,
/
CH3OH); 1H NMR (300 MHz, Me2SO): d 1.95 (s, 3 H,
Ac), 2.00 (s, 3 H, Ac), 2.01 (s, 3 H, Ac), 2.80 (dd, 1 H, J
/
5.0 and 11.5 Hz, H-5), 2.93ꢀ3.02 (m, 3 H, CH2, H-5?),
/
/
3.50 (m, 1 H, H-1), 4.92 (m, 1 H, H-4), 5.09 (dd, 1 H, J
4.5 and 10.0 Hz, H-2), 5.16 (t, 1 H, J 10.0 Hz, H-3), 7.77
(m, 4 H, Ar,), 10.5 (s, 1 H, NHCO). Anal. Calcd For
C20H22N2O7S: C, 55.29; H, 5.10; N, 6.45. Found: C,
55.27; H, 5.18; N, 6.19.
/
/
/
/
126.
27. Allevi, P.; Anastasia, M.; Ciuffreda, P.; Scala, A. J.
References
Carbohydr. Chem. 1993, 12, 209ꢀ
28. Garcia Lopez, M. T.; De las Heras, F. G.; San Felix, A. J.
Carbohydr. Chem. 1987, 6, 273ꢀ279.
29. Drew, K. N.; Gross, P. H. J. Org. Chem. 1991, 56, 509ꢀ
/
222.
1. Bellamy, F.; Horton, D.; Millet, J.; Picart, F.; Samreth, S.;
Chazan, J. B. J. Med. Chem. 1993, 36, 898ꢀ
/903.
/
2. Samreth, S.; Barberousse, V.; Bellamy, F.; Horton, D.;
/
Masson, P.; Millet, J.; Renaut, P.; Sepulchre, C.; Theve-
513.
30. Giese, B.; Dupuis, J.; Leising, M.; Nix, M.; Lindner, H. J.
niaux, J. Trends Recept. Res. 1993, 20, 41ꢀ
/
59.
3. Bellamy, F.; Barberousse, V.; Martin, N.; Masson, P.;
Carbohydr. Res. 1987, 171, 329ꢀ
31. Tucker, C. E.; Magid, T. N.; Knochel, P. J. Am. Chem.
Soc. 1992, 114, 3983ꢀ3985.
32. Bihovsky, R.; Selick, C.; Giusti, J. J. Org. Chem. 1988, 53,
4026ꢀ4031.
33. (a) Panigot, M. J.; Curley, R. W., Jr. J. Carbohydr. Chem.
1994, 13, 293ꢀ302;
(b) Panigot, M. J.; Humphries, K. A.; Curley, R. W., Jr. J.
Carbohydr. Chem. 1994, 13, 303ꢀ321.
34. Ogawa, T.; Pernet, A. G.; Hanessian, S. Tetrahedron Lett.
1973, 37, 3543ꢀ3546.
35. Hoffmann, M. G.; Schmidt, R. R. Liebigs Ann. Chem.
1985, 2403ꢀ2419.
36. Davidson, A. H.; Hughes, L. R.; Qureshi, S. S.; Wright, B.
Tetrahedron Lett. 1988, 29, 693ꢀ696.
37. Green, M. J. Chem. Soc. 1963, 1324ꢀ
38. Mbongo, A.; Frechou, C.; Beaupe`re, D.; Uzan, R.;
Demailly, G. Carbohydr. Res. 1993, 246, 361ꢀ370.
39. Dawe, R. D.; Fraser-Reid, B. J. Org. Chem. 1984, 49,
522ꢀ528.
40. Horton, D.; Koh, D. Carbohydr. Res. 1993, 250, 231ꢀ
41. Theveniaux, J.; Millet, J. Unpublished results.
42. Condon, S.; Dupre, D.; Fargayrac, G.; Nedelec, J.-Y. Eur.
J. Org. Chem. 2002, 1, 105ꢀ111.
43. (a) Bajic, M.; Kumar, A.; Boykin, D. W. Heterocyclic
Commun. 1996, 2, 135ꢀ140;
(b) Yokokawa, F.; Asano, T.; Shioiri, T. Tetrahedron
2001, 57, 6311ꢀ6327;
(c) Aggarwal, V. K.; Sheldon, C. G.; MacDonald, G. J.;
Martin, W. P. J. Am. Chem. Soc. 2002, 124, 10300ꢀ10301.
/341.
Millet, J.; Samreth, S.; Sepulchre, C.; Theveniaux, J.;
Horton, D. Euro. J. Med. Chem. 1995, 30, 101sꢀ
/115s.
/
4. Samreth, S.; Barberousse, V.; Bellamy, F.; Horton, D.;
Masson, P.; Millet, J.; Renaut, P.; Sepulchre, C.; Theve-
/
niaux, J. Actual. Chim. Ther. 1994, 21, 23ꢀ
5. Okayama, M.; Kimata, K.; Suzuki, S. J. Biochem.
(Tokyo) 1973, 74, 1069ꢀ1073.
6. Schwartz, N. B. J. Biol. Chem. 1977, 252, 6316ꢀ
7. Guichard, J.P.; Guillou, F. Unpublished results.
8. Postema, M. H. D. Tetrahedron 1992, 48, 8545ꢀ
/
33.
/
/
/6321.
/
/8599.
/
9. (a) Levy, D. E.; Tang, C. The Chemistry of C-glycosides;
Pergamon Elsevier Science Ltd: Oxford, 1995;
(b) Postema, M. H. D. C-Glycoside Synthesis; CRC Press:
Boca Raton, FL, 1995.
/
/
10. Belosludtsev, Y. Y.; Bhatt, R. K.; Falck, J. R. Tetrahedron
/
1327.
Lett. 1995, 36, 5881ꢀ
/
5882.
11. Wang, X.; Gross, P. H. J. Org. Chem. 1995, 60, 1201ꢀ
/
/
1206.
12. Mazeas, D.; Skrydstrup, T.; Beau, J. M. Angew. Chem.,
/
Int. Ed. Engl. 1995, 34, 909ꢀ
13. Mata, F. Z.; Martinez, M. B.; Perez, J. A. G. Carbohydr.
Res. 1992, 225, 159ꢀ161.
14. Toshima, K.; Matsuo, G.; Tatsuta, K. Tetrahedron Lett.
1992, 33, 2175ꢀ2178.
15. Jaramillo, C.; Knapp, S. Synthesis 1994, 1ꢀ
16. Dheilly, L.; Frechou, C.; Beaupere, D.; Uzan, R.; De-
mailly, G. Carbohydr. Res. 1992, 224, 301ꢀ306.
17. Lopez, R.; Fernandez-Mayoralas, A. J. Org. Chem. 1994,
59, 737ꢀ745.
18. Boyd, V. A.; Drake, B. E.; Sulikowski, G. A. J. Org.
Chem. 1993, 58, 3191ꢀ3193.
/912.
/247.
/
/
/
/
20.
/
/
/
/
/
44. Samreth, S.; Millet, J.; Bellamy, F.; Bajgrowicz, J.;
/
Barberousse, V. EP-365 397; Chem. Abstr. 1991, 114, 858.