A New Approach to the Synthesis of Benzothiazole, Benzoxazole, and Pyridine Nucleosides as Potential Antitumor Agents

Article abstract of DOI:10.1081/NCN-120026407

A modified nitrogen and sulfur glycosylation reaction involving benzothiazole benzoxazole and pyridine nucleoside bases with furanose and pyranose sugars are described. Conformational analysis has been studied by homo- and heteronuclear two-dimensional NMR methods (2D DFQ-COSY, HMQC and HMBC). The N and S sites of glycosylation were determined from the ¹H, ¹³C heteronuclear multiple-quantum coherence (HMQC) experiments. All the deprotected nucleosides were tested for their potential antitumor activity.

Full text of DOI:10.1081/NCN-120026407

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A New Approach to the Synthesis of Benzothiazole,
Benzoxazole, and Pyridine Nucleosides as Potential
Antitumor Agents
Ahmed I. Khodair a d , Najim A. Al-Masoudi b & Jean-Pierre Gesson c
a Chemistry Department , Faculty of Education , Tanta University (Kafr El-Sheikh Branch) ,
Kafr El-Sheikh, Egypt
b Fakultät für Chemie , Universität Konstanz , Konstanz, Germany
c Laboratoire de Chimie XII , Université de Poitiers et CNRS , Poitiers, France
d Chemistry Department , Faculty of Education , Tanta University (Kafr El-Sheikh Branch) ,
Kafr El-Sheikh, Egypt
Published online: 31 Aug 2006.
To cite this article: Ahmed I. Khodair , Najim A. Al-Masoudi & Jean-Pierre Gesson (2003) A New Approach to the Synthesis of
Benzothiazole, Benzoxazole, and Pyridine Nucleosides as Potential Antitumor Agents, Nucleosides, Nucleotides and Nucleic
Acids, 22:11, 2061-2076, DOI: 10.1081/NCN-120026407
To link to this article: http://dx.doi.org/10.1081/NCN-120026407
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, No. 11, pp. 2061–2076, 2003
A New Approach to the Synthesis of Benzothiazole,
Benzoxazole, and Pyridine Nucleosides as
Potential Antitumor Agents
2
3
Ahmed I. Khodair,1, Najim A. Al-Masoudi, and Jean-Pierre Gesson
*
1Chemistry Department, Faculty of Education, Tanta University
(Kafr El-Sheikh Branch), Kafr El-Sheikh, Egypt
2Fakulta¨t fur Chemie, Universita¨t Konstanz, Konstanz, Germany
¨
Laboratoire de Chimie XII, Universite de Poitiers et CNRS,
Poitiers, France
3
´
ABSTRACT
A modified nitrogen and sulfur glycosylation reaction involving benzothiazole
benzoxazole and pyridine nucleoside bases with furanose and pyranose sugars
are described. Conformational analysis has been studied by homo- and hetero-
nuclear two-dimensional NMR methods (2D DFQ-COSY, HMQC and HMBC).
The N and S sites of glycosylation were determined from the 1H, 13C hetero-
nuclear multiple-quantum coherence (HMQC) experiments. All the deprotected
nucleosides were tested for their potential antitumor activity.
*Correspondence: Ahmed I. Khodair, Chemistry Department, Faculty of Education, Tanta
University (Kafr El-Sheikh Branch), Kafr El-Sheikh, Egypt; Fax: 20-472-23415; E-mail:
khodair_62@yahoo.com.
2061
DOI: 10.1081/NCN-120026407
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

2062
Khodair, Al-Masoudi, and Gesson
INTRODUCTION
Important biological processes are carried out by carbohydrate processing
enzymes and in particular by glycosides.[1–3] Their roles in therapeutic and biological
applications as a consequence of modifying or blocking their action have attracted
the attention of organic chemists and biochemists. These strategies have been applied
to glycosides involved in intestinal digestion, post-translational processing of glyco-
proteins, and lysosomal catabolism of glycoconjugates. Thus, a number of them show
promise as antidiabetes,[4] antitumor metastasis,[5] and antiobesity drugs,[6] and as
antifeedents[7] and antivirals.[8–11] We have recently reported that S-glycosylated
hydantoin derivatives showed potent activity against the herpes simplex virus
(HSV),[12] the human immunodeficiency virus (HIV)[13] and the leukemia sub-
panel.[14] The importance of such compounds prompted our interest in the synthesis
and chemistry of this type of compounds. In the course of identifying new chemical
structures which may serve as leads for designing novel antitumor and antiviral
agents, we were particularly interested in S-glycosylation of 2-thiohydantoins.[12–16]
In this respect, it seemed worth-while to link the benzothiazole, benzoxazole and pyri-
dine to an hydrophilic moiety such as a glycoside. It was thus anticipated a better
water solubility of these heterocycles and an improved selectivity toward cancer cells
which are known to be specifically enriched in carbohydrate receptors such as
lectins.[17,18] The present work describes the synthesis of a series of nitrogen glycosyl-
ated and their sulfur analogues bearing benzothiazole, benzoxazole and pyridine
bases via new synthetic strategies. Furthermore, the confirmation of their most stable
conformation and the antitumor screening has been studied.
RESULTS AND DISCUSSION
The silylation of the nucleoside bases 1a–c was accomplished with bis(trimethyl-
silyl)-acetamide (BSA) in anhydrous MeCN at 70–80ꢀC, and furnished the trimethyl-
silylated derivatives 2a–c. These derivatives were condensed, devised by Vorbruggen
¨
et al.,[21] with 1,2,3,5-tetra-O-acetyl-b-d-ribofuranose (3) in the presence of trimethyl-
silyl trifluoromethyanesulfonate (TMSOTf) as a catalyst at 70–80ꢀC for 60 min. The
nucleosides 4a,b[22] were isolated by silica gel column chromatography in 72–76%
yields. Removal of the acetyl groups from the glycon moiety of 4a,b with 16%
NH3=MeOH solution at r. t. furnished 3-(b-d-ribofuranosyl)-2-thiobenzothiazole
(5a)[22] and 3-(b-d-ribofuranosyl)-2-thiobenzoxazole (5b)[22] instead of N-(hydroxy-
2-phenyl)-N-(b-d-ribofuranosyl)thiocarbamide,[22] respectively (Sch. 1). The proton
spin systems were identified from DFQ-COSY[23] spectra. The anomeric coupling
constants of 5a is a typical for the b-configurated ribofuranoses (7.5 Hz). The rota-
ting from nuclear overhauser effect (NOE)[24–26] between 10-H at dH 6.84 and 40-H is
an additional proof for b-configuration, and these data are in agreement with those
reported earlier by Gosselin et al.[22] The ribosylation occurred at the N-site of the
benzothiazole 1a. This was also visible in the HMBC spectrum where the anomeric
proton of 5a showed cross peak to C-3a (only one rotator about the glycosidic link-
age was observed), and no such correlation to C-7a was shown, indicating for the
N-glycosylation and not the S-glycosylation. Protons bearing carbon were detected

Benzothiazole and Benzoxazole Nucleosides
2063
Scheme 1. Reagents and conditions: (a) MeCN, BSA, 70–80ꢀC; (b) 1,2,3,5-tetra-O-acetyl-b-
d-ribofuranose (3), TMSOTf, 70–80ꢀC; (c) 16% NH3=MeOH, r. t.
in HMQC spectra.[27] Carbon 2 resonates at highest field (dC 191.2) due to the shield-
ing nature around thiocarbonyl bond, proving the N-glycosylation and excluding
substitution at the sulfur atom (Sch. 1). These data are also in agreement with the
13C-NMR spectrum of 3-(4-morpholinomethyl)-2-thiobenzothiazole 8,[28] which in
turn was prepared from the reaction of 1a with morpholine and formaldehyde in
EtOH at r. t., since the thiocarbonyl group at C-2 appears at dC 190.1 (Sch. 2). More
evidence for the formation of N-nucleoside 4a was obtained from the comparison
with the spectral data obtained by Schantle et al.[29] during the N-methylation
of N-substituted 4-methyl-5-phenyl-1H-imidazole-2-thione. On the other hand,

2064
Khodair, Al-Masoudi, and Gesson
Scheme 2. Reagents and conditions: (a) Allyl iodide, NaOH, H2O, r. t.; (b) HCHO, morpho-
line, EtOH, r. t.
2c was condensed with 3 under the same above conditions to give 6 (78%), after
purification by chromatography. Deblocking of 6 with 16% NH3=MeOH solution
1
at r. t. furnished 7 (Sch. 1). The structure of 7 was established on its H, 13C-
0
0
NMR and mass spectra. The doublet at d 5.80 (J1 ,2 4.57 Hz) was attributed to
the anomeric proton of the b-configuration, whereas the 13C NMR spectrum was
characterized by a singlet at d 166.1, corresponding to C-2, then proving S-glycosyla-
tion and excluding substitution at the nitrogen atom (Sch. 1).
These data are in agreement with the 13C-NMR spectrum of 2-allylmercapto-
benzothiazole (9),[30] which was prepared from the reaction of 1a with allyl iodide
in aqueous NaOH at r. t. and characterized by the appearance of the mercapto group
at dC 165.9. (Sch. 2). Again, these data are also in agreement with those of S-methy-
lation of some derivatives of N-substituted-1H-imidazole-2-thione.[29]
When compound 1a was reacted with 1.1 equivalent of NaH in anhydrous
MeCN followed by the addition of 1.1 equivalent of 2,3,4,6-tetra-O-acetyl-b-d-glu-
copyranosyl bromide(10),[31] the 2-(20,30,40,60-tetra-O-acetyl-b-d-glucopyranosyl)-2-
thiobenzothiazole (13a)[32] and 3-(20,30,40,60-tetra-O-acetyl-b-d-glucopyranosyl)-2-
thiobenzothiazole (14a)[32] in 84 and 4% yield, respectively, were obtained. Similarly,
the treatment of compounds 1b and 1c with 2,3,4,6-tetra-O-benzoyl-b-d-glucopyra-
nosyl bromide (11)[31] and 10 under the same above conditions afforded 2-(20,30,40,60-
tetra-O-benzoyl-b-d-glucopyranosyl)-2-thiobenzoxazole (13b) and 5-methoxy-2-
(20,30,40,60-tetra-O-acetyl-b-d-glucopyranosyl)-2-thiobenzothiazole (13c) in 82 and
83% yield, respectively.
This series was extended with more sugar moieties such as the acylated galactose
bromide[33] bearing the benzothiazole precursors to examine their potential biologi-
cal activity. Thus, the galactose bromide derivative 12 was selected to react with: 1a,
giving 13d[34] in 90% yield, 1b affording 13e in 45% yield and 14b in 38% yield,
and finally with 1c to yield 13f in 60% yield and 14c in 22% yield, respectively.
Deprotection of 13a–f and 14b,c with saturated 16% NH3=MeOH solution at r. t.
furnished the corresponding free nucleosides 15a–f and 16a,b, respectively (Sch. 3).

Benzothiazole and Benzoxazole Nucleosides
2065
Scheme 3. Reagents and conditions: (a) NaH, MeCN, r. t.; (b) 2,3,4,6-tetra-O-acetyl-a-d-gluco-
pyranosyl bromide (10) or 2,3,4,6-tetra-O-benzoyl-a-d-glucopyranosyl bromide (11) or
2,3,4,6-tetra-O-acetyl-a-d-galactopyranosyl bromide (12), r. t.; (c) 16% NH3=MeOH, r. t.
The structures of 15a–f and 16a,b were confirmed on the basis of their spectroscopic
and mass spectral data and the earlier results of Zinner and Peseke.[32] The mass
1
spectrum of 15e showed a molecular ion peak at m=z 313, while the H-NMR spec-
trum showed a doublet at dH 5.36 with J1 ,2 9.8 Hz, corresponding to the 10-H and
indicating a b-configuration. C-2 of 15e resonated at dC 162.5, establishing the S-gly-
cosylation. The structure of 16a was assigned from the mass (molecular ion peak at
m=z 313), 1H and 13C-NMR spectra. The anomeric proton appeared as a doublet at
0
0

2066
Khodair, Al-Masoudi, and Gesson
0
0
dH 6.03 (J1 ,2 9.1 Hz), corresponding to the diaxial coupling and then the b-con-
figuration. The 13C NMR spectrum was characterized by a singlet at dC 181.4, cor-
responding to C-2, and then proving the N-glycosylation. Furthermore, the
3
heteronuclear spectra (HMQC, DFQ-COSY) of 16a,b showed JC,H correlation
between C-3a and 10-H, which is an additional proof for N-glycosylation, since no
such correlation was shown by 15a-f, which is indication of the S-glycosylation.
When 2-mercapto-pyridine 17 was reacted with 1.1 equivalent of NaH in anhy-
drous MeCN followed by addition of 1.1 equivalent of 10 and 12, two products
18a[35] and 18b[35] were isolated in 77 and 86% yields, respectively. On the other
hand, silylation of 17 with BSA in anhydrous MeCN at 70–80ꢀC afforded the tri-
methylsilylated derivative 20. Condensation of 20, by applying Vorbruggen et al.[21]
¨
method, with 3 in the presence of TMSOTf as catalyst at 70–80ꢀC for 60 min gave,
after purification by column chromatography, 21[36] (72% yield). Deblocking of
18a,b and 21 with 16% NH3=MeOH solution at r. t. furnished 19a[37] (85%),
19b (97%) and 22 (90%), respectively (Sch. 4). The structures of 18–22 were identified
by the spectroscopic methods, since the structure of 19b was supported by the mass
Scheme 4. Reagents and conditions: (a) 10 or 12, NaH, MeCN, r. t.; (b) 16% NH3=MeOH, r. t.;
(c) MeCN, BSA, 70–80ꢀC; (d) 3, TMSOTf, 70–80ꢀC.

Benzothiazole and Benzoxazole Nucleosides
2067
spectra, which showed a molecular ion peak at m=z 273. 10-H appeared as a doublet
0
0
at dH 5.07 with J1 ,2 9.7 Hz, confirming the diaxial coupling with the b-configuration.
C-2 at 19b resonates at dC 158.8, proving the S-glycosylation and excluding substitu-
tion at the nitrogen atom. The mass spectrum of 21 was characterized by a molecular
0
0
ion peak at m=z 369, while the resonance at dH 6.09 (J1 ,2 4.6 Hz) as a doublet was
attributed to 10-H with a b-configuration, and these data are in agreement with
the 1H-NMR data of 1-(2-thiopyridyl-2,3-O-isopropylidene-5-O-(tert-butyldiphenyl-
silyl)-b-d-ribofuranose and its a-anomer (the anomeric protons appeared at dH
6.19 and 6.68, respectively).[38] The 13C NMR spectrum of compound 22 was cha-
racterized by a singlet at dC 158.1, corresponding to C-2, and again proving the
S-glycosylation.
In conclusion, we have described the successful syntheses of benzothiazole, benz-
oxazole and pyridine nucleosides bearing the furanose and pyranose sugar moieties,
and established their configuration and most stable conformation by analysis of their
spectral data (ROESY, DFQ-COSY, HMBC and HMQC NMR spectra). Com-
pounds 5a,b, 15a–f, 16a,b, 19a,b and 22 were screened against leukemia-1210[39,40]
and were found to be inactive. The antiviral and the other antitumor activities of
the prepared compounds are under investigation.
EXPERIMENTAL
General Methods. Melting points (ꢀC) are uncorrected. Aluminum sheets
coated with silica gel 60 F254 (Merck) were used for TLC. Viewing under a short
wavelength UV lamp effected detection. IR spectra (KBr disc) were obtained on a
Pye Unicam spectra 1000. NMR spectra were measured in DMSO-d6 and CDCl3
using SiMe4 as internal reference on a Bruker Advance DPX 300 MHz spectrometer.
Analytical data were obtained from the Service Central de Microanalyse (CNRS,
Lyon). Mass spectra were recorded by EI on a Varian MAT 311A spectrometer
and FAB on a Kratos MS 50 spectrometer.
3-(20,30,50-Tri-O-acetyl-b-d-ribofuranosyl)-2-thiobenzothiazole (4a). General
Procedure: A suspension of 1a (835 mg, 5.0 mmol) in anhydrous MeCN (25 mL)
and BSA (1.25 mL, 5.0 mmol) was heated at 70–80ꢀC for 30 min. 1,2,3,5-Tetra-O-
acetyl-b-d-ribofuranose (3) (1.75 g, 5.0 mmol) dissolved in anhydrous MeCN
(25 mL) was added to the reaction mixture via a cannula, followed by the addition
of TMSOTf (1.0 mL, 1.0 mmol) and the reaction mixture was heated at 70–80ꢀC
for 1 h. After cooling, a saturated aqueous NaHCO3 solution was added and the
resulting mixture extracted with CH2Cl2. The combined organic fractions were
washed with saturated NaCl solution, dried (MgSO4), filtered, and evaporated to
dryness. The residue obtained was purified by flash chromatography (eluent EtOAc=
petroleum ether 40–60ꢀC, 1:3) to give 4a (1.62 g, 76%) as a white foam (lit.[22] mp
1
134–136ꢀC, 75%). MS; m=z: 425 (Mþ). H-NMR (CDCl3): d 2.05, 2.16, 2.22, (3s,
9H, 3 Ac), 4.12 (dd, J ¼ 7.1, 7.1 Hz, 1H, 50-H), 4.36 (m, 2H, 40-H, 500-H), 5.52 (dd,
J ¼ 4.3, 6.7 Hz, 1H, 30-H), 5.79 (dd, J ¼ 6.9, 6.9 Hz, 1H, 20-H), 7.22 (d, J ¼ 6.8 Hz,
1H, 10-H), 7.27–7.62 (m, 4H, Ar-H). 13C-NMR (CDCl3): d 20.3, 20.5, 20.8 (3 Ac),

2068
Khodair, Al-Masoudi, and Gesson
62.6 (C-50), 68.7 (C-30), 69.7 (C-20), 79.4 (C-40), 88.1 (C-10), 113.2, 121.4, 125.1, 125.9,
126.7, 139.4 (C-Ar), 169.4, 169.7, 170.1 (3 CO), 191.8 (C-2).
3-(20,30,50-Tri-O-acetyl-b-d-ribofuranosyl)-2-thiobenzoxazole (4b). From 1b
(755 mg, 5.0 mmol) in the manner described for 4þa. Yield 1.47 g (72%) as a white foam
1
(lit.[22] mp 107–108ꢀC, 47%). MS; m=z: 409 (M ). H-NMR (CDCl3): d 2.07, 2.18;
2.21 (3s, 9H, 3 Ac), 4.12 (dd, J ¼ 7.0, 7.1 Hz, 1H, 50-H), 4.40 (m, 2H, 40-H, 500-H),
5.48 (dd, J ¼ 4.4, 6.7 Hz, 1H, 30-H), 5.70 (dd, J ¼ 6.9, 6.9 Hz, 1H, 20-H), 6.67 (d,
1H, J ¼ 7.0 Hz, 10-H), 7.24–7.47 (m, 4H, Ar-H). 13C-NMR (CDCl3): d 20.2, 20.4,
20.6 (3 Ac), 62.7 (C-50), 69.2 (C-30), 70.0 (C-20), 79.9 (C-40), 88.3 (C-10), 110.4,
110.8, 124.6, 124.7, 128.9, 146.8 (C-Ar), 169.3, 169.5, 169.9 (3 CO), 180.1 (C-2).
3-(b-d-Ribofuranosyl)-2-thiobenzothiazole (5a). General Procedure: To a stirred
solution of 4a (850 mg, 2.0 mmol) in anhydrous MeOH (20 mL) was added a solution
of 16% NH3=MeOH (10 mL) at r. t. and the stirring was continued for 16 h. The sol-
vent was evaporated and the residue was chromatographed on silica gel using
MeOH, in gradient, (0–5%) and CH2Cl2 as eluent to give 5a (514 mg, 86%) as a white
1
solid, mp 129–131ꢀC (lit.[22] mp 153–154ꢀC, 91%). MS; m=z: 299 (Mþ). H-NMR
(DMSO-d6): d 3.73 (m, 2H, 50-H, 500-H), 3.92 (m, 1H, 40-H), 4.17 (dd, J ¼ 4.9,
5.0 Hz, 1H, 30-H), 4.55 (dd, J ¼ 6.6, 7.1 Hz, 1H, 20-H), 5.19 (d, J ¼ 4.9 Hz, 1H, 30-
OH), 5.24 (t, J ¼ 4.9 Hz, 1H, 50-OH), 5.34 (d, J ¼ 6.5 Hz, 1H, 20-OH), 6.84 (d,
J ¼ 7.5 Hz, 1H, 10-H), 7.28–8.08 (m, 4H, Ar-H). 13C-NMR (DMSO-d6): d 61.1
(C-50), 69.2 (C-30), 70.2 (C-20), 85.9 (C-40), 90.2 (C-10), 115.3, 121.8, 125.1, 125.8,
127.1, 139.7 (C-Ar), 191.2 (C-2).
3-(b-d-Ribofuranosyl)-2-thiobenzoxazole (5b). From 4b (818 mg, 2.0 mmol) in
the manner described for 5a. Yield 475 mg (84%þ) as a white solid, mp 206–208ꢀC
1
(lit.[22] mp 183–185ꢀC, 75%). MS; m=z: 283 (M ). H-NMR (DMSO-d6): d 3.74
(m, 2H, 50-H, 500-H), 4.02 (m, 1H, 40-H), 4.21 (m, 1H, 30-H), 4.53 (dd, J ¼ 6.2,
7.3 Hz, 1H, 20-H), 5.12 (d, J ¼ 4.8 Hz, 1H, 30-OH), 5.16 (t, J¼4.7 Hz, 1H, 50-OH),
5.32 (d, J ¼ 6.1 Hz, 1H, 20-OH), 6.36 (d, J ¼ 7.4 Hz, 1H, 10-H), 7.25–8.00 (m, 4H,
13
Ar-H). C-NMR (DMSO-d6): d 61.1 (C-50), 69.6 (C-30), 70.9 (C-20), 85.9 (C-40),
90.6 (C-10), 109.8, 112.9, 124.2, 124.8, 129.3, 146.5 (C-Ar), 180.12 (C-2).
5-Methoxy-2-(20,30,50-tri-O-acetyl-b-d-ribofuranosylmercapto)benzothiazole (6).
From 1c (985 mg, 5.0 mmol) in the manner described for 4a. Yield 1.77 g (78%) of
6 as pale yellow foam. MS; m=z: 455 (Mþ). Calculated for C19H21NO8S2 (455.49):
C, 50.10; H, 4.65; N, 3.07. Found: C, 49.86; H, 4.53; N, 2.84. [a]D þ 21ꢀ (c 0.7,
1
CHCl3). H-NMR (CDCl3): d 2.10, 2.13, 2.14 (3s, 9H, 3 Ac), 3.86 (s, 3H, OCH3),
4.12 (dd, J ¼ 7.1, 7.1 Hz, 1H, 50-H), 4.46 (m, 2H, 40-H, 500-H), 5.47 (dd, J ¼ 5.2,
5.2 Hz, 1H, 30-H), 5.60 (dd, J ¼ 4.5, 4.8 Hz, 1H, 20-H), 6.14 (d, J ¼ 4.3 Hz, 1H, 10-H),
6.96–7.63 (m, 3H, Ar-H). 13C-NMR (CDCl3): d 20.0, 20.1, 20. 6 (3 Ac), 55.2
(OCH3), 62.6 (C-50), 70.8 (C-30), 74.3 (C-20), 80.3 (C-40), 86.9 (C-10), 104.6,
114.4, 120.9, 126.9, 153.9, 158.6 (C-Ar), 162.7 (C-2), 168.9, 169.2, 169.9 (3 CO).
5-Methoxy-2-(b-d-ribofuranosylmercapto)benzothiazole (7). From 6 (910 mg,
2.0 mmol) in the manner described for 5a. Yield 580 mg (88%) as a white solid,

Benzothiazole and Benzoxazole Nucleosides
2069
mp 125–127ꢀC. MS; m=z: 329 (Mþ). Calculated for C13H15NO5S2 (329.38): C, 47.40;
H, 4.59; N, 4.25. Found: C, 47.22; H, 4.82; N, 3.93. [a]D ꢁ25ꢀ (c 0.5, MeOH).
1H-NMR (DMSO-d6): d 3.50 (m, 2H, 50-H, 500-H), 3.84 (s, 3H, OCH3), 3.90
(m, 1H, 40-H), 4.04 (m, 1H, 30-H), 4.15 (m, 1H, 20-H) 4.87 (br. s, 1H, 30-OH), 5.24
(br. s, 1H, 50-OH), 5.65 (br. s, 1H, 20-OH), 5.80 (d, J ¼ 4.6 Hz, 1H, 10-H), 7.01–7.90
13
(m, 3H, Ar-H). C-NMR (DMSO-d6): d 55.7 (OCH3), 61.8 (C-50), 70.9 (C-30),
75.6 (C-20), 86.5 (C-40), 89.8 (C-10), 104.9, 114.2, 122.3, 126.7, 154.1, 158.9
(C-Ar), 166.0 (C-2).
3-(4-Morpholinomethyl)-2-thiobenzothiazole (8). A mixture of 1a (167 mg,
1.0 mmol) and morpholine (87 mg, 1 mmol) in anhydrous EtOH (5 mL) and aqueous
formaldehyde (1 mL) was stirred for 6 h at r. t. until the starting material was con-
sumed (TLC). The separated solid was collected by filtration and recrystallized from
EtOH to give 245 mg (92%) of 8 as a white solid, mp 140–142ꢀC (lit.[28] mp
149–150ꢀC, 79%). MS; m=z ¼ 266 (Mþ). 1H NMR (DMSO-d6): d 2.66 (m, 4H, 20-H,
60-H), 3.52 (m, 4H, 30-H, 50-H), 5.15 (s, 2H, NCH2N), 7.36–7.74 (m, 4H, Ar-H);
13C NMR (DMSO-d6): d 50.9 (C-20, C-60), 65.8 (C-30, C-50), 65.9 (CH2), 114.4,
121.9, 124.8, 125.3, 126.9, 141.6 (C-Ar), 190.1 (C-2).
2-Allylmercaptobenzothiazole (9). To a solution of 1a (167 mg, 1.0 mmol) in 1%
aqueous NaOH (5 mL) was added allyl iodide (185 mg, 1.1 mmol) at r. t., with stir-
ring. After 16 h at the same temperature, an aqueous solution of saturated NaHCO3
was added and the reaction mixture was extracted with CH2Cl2 (3 ꢂ 10 mL). The
combined organic extract was washed with saturated NaCl solution, dried (MgSO4),
filtered, and evaporated to dryness. The residue was purified by flash chromatogra-
phy (eluent: EtOAc=pet. ether 40–60ꢀC, 10–30%) to afford 9 (200 mg, 96%) as pale
1
yellow oil (lit.,[30] oil). MS; m=z: 207 (Mþ). H-NMR (CDCl3): d 3.95 (m, 2H,
CH2), 5.14–5.37 (m, 2H, NCH2), 6.00 (m, 1H, ¼ CH), 7.22–7.87 (m, 4H, Ar-H).
13C-NMR (CDCl3): d 35.9 (CH2), 118.9 (¼ CH), 120.7 (NCH2), 121.3, 124.0,
125.62, 132.1, 135.1, 153.0 (C-Ar), 165.9 (C-2).
2-(20,30,40,60-Tetra-O-acetyl-b-d-glucopyranosylmercapto)benzothiazole (13a) and
3-(20,30,40,60-Tetra-O-acetyl-b-d-glucopyranosyl)-2-thiobenzothiazole (14a). General
Procedure: To a suspension of 1a (0.85 g, 5 mmol) in anhydrous MeCN (5 mL) at
r. t. was added NaH (50%, 0.26 g, 5.0 mmol), and the mixture was stirred at the same
temperature for 30 min. The mixture became clear after 15 min. The sugar bromide
10 (2.26 g, 5.5 mmol) was added, and the mixture was stirred at r. t. for 12 h until
the starting material was consumed (TLC) and then filtered. Evaporation of the fil-
trate afforded an oil, purified by flash chromatography (eluent: EtOAc=pet. ether,
40–60ꢀC, 10–30%,) to afford 13a (2.10 g, 84%) as a white foam (lit.,[32] mp 138–139ꢀC,
34%) and 0.01 g (4%) of 14a as pale yellow foam (lit.,[32] mp 195–196ꢀC, 3.8%).
1
13a: MS; m=z: 497 (Mþ). H-NMR (CDCl3): d 2.03, 2.04, 2.05 (3s, 9H, 3 Ac),
3.94 (ddd, J ¼ 2.2, 4.7, 6.9 Hz, 1H, 50-H), 4.20 (dd, J ¼ 2.0, 12.4 Hz, 1H, 60-H),
4.33 (dd, J ¼ 4.9, 12.4 Hz, 1H, 600-H), 5.15–5.26 (m, 2H, 20-H, 40-H), 5.36 (dd,
J ¼ 9.2, 10.1 Hz, 1H, 30-H), 5.60 (d, J ¼ 10.2 Hz, 1H, 10-H), 7.30–7.95 (m, 4H,
13
Ar-H). C-NMR (CDCl3): d 20.4, 20.5, 20.6 (4 Ac), 61.7 (C-60), 67.9 (C-20), 69.5

2070
Khodair, Al-Masoudi, and Gesson
(C-30), 73.6 (C-40), 76.1 (C-50), 83.8 (C-10), 120.9, 122.2, 124.9, 126.3, 135.6, 152.5
(C-Ar); 161.7 (C-2), 169.2, 169.3, 169.9, 170.4 (4 CO).
1
14a: MS; m=z 497 (Mþ). H-NMR(CDCl3): d 2.03, 2.05 2.08, 2.12 (4s, 12H, 4
Ac), 4.08 (m, 1H, 50-H), 4.30 (m, 2H, 60-H, 600-H), 5.26 (dd, J ¼ 9.7, 10.1 Hz, 1H, 40-
H), 5.57 (dd, J ¼ 9.2, 9.5 Hz, 1H, 20-H), 5.76 (dd, J ¼ 9.4, 9.4 Hz, 1H, 30-H), 6.93 (d,
1H, J ¼ 9.5 Hz, 1H, 10-H), 7.28–7.7.90 (m, 4H, Ar-H).
2-(20,30,40,60-Tetra-O-benzoyl-b-d-glucopyranosylmercapto)benzoxazole (13b).
From 1b (0.76 g, 5.0 mmol) and 11 (3.62 g, 5.5 mmol) in the manner described
for 13a. Yield 0.60 g (82%) as white foam. MS; m=z: 729 (Mþ). Calculated for
C41H31NO10S (729.75): C, 67.48; H, 4.28; N, 1.92. Found: C, 67.12; H, 4.59; N,
1
1.78. [a]D þ 54ꢀ (c 1.2, CHCl3). H-NMR (CDCl3): d 4.48 (dd, J ¼ 4.5, 5.8 Hz,
2H, 60-H, 600-H), 4.64 (dd, J ¼ 5.6, 5.6 Hz, 1H, 50-H), 5.69–5.81 (m, 2H, 30-H,
40-H), 6.07–6.14 (m, 2H, 10-H, 20-H), 7.22–7.7.95 (m, 24H, Ar-H). 13C-NMR
(CDCl3): d 63.1 (C-60), 69.2 (C-20), 70.4 (C-30), 73.9 (C-40), 77.0 (C-50), 83.7
(C-10), 110.11–151.9 (C-Ar), 161.1 (C-2), 165.16, 165.3, 165.7, 166.1 (4 CO).
5-Methoxy-2-(20,30,40,60-tetra-O-acetyl-b-d-glucopyranosylmercapto)benzothiazole
(13c). From 1c (1.15 g, 5.0 mmol) in the manner described for 13a. Yield 0.88 g
(83%) as pale yellow foam. MS; m=z: 527 (Mþ). Calculated for C22H25NO10S2
(527.56): C, 50.09; H, 4.78; N, 2.66. Found: C, 49.87; H, 5.08; N, 2.80. [a]D þ 72ꢀ
1
(c 0.7, CHCl3). H-NMR (CDCl3): d 2.03, 2.05, 2.06, 2.70 (4s, 12H, 4 Ac), 3.88
(s, 3H, OCH3), 3.94 (ddd, J ¼ 2.6, 5.0, 7.5 Hz, 1H, 50-H), 4.21 (d, J ¼ 12.4 Hz, 1H,
60-H), 4.30 (dd, J ¼ 4.9, 12.4 Hz, 1H, 600-H), 5.15-5.25 (m, 2H, 20-H, 40-H), 5.40
(m, 1H, 30-H), 5.54 (d, J ¼ 10.2 Hz, 1H, 10-H), 7.00–7.65 (m, 3H, Ar-H). 13C-NMR
(CDCl3): d 20.3, 20.3, 20.4, 20.7 (4 Ac), 55.4 (OCH3), 61.6 (C-60), 67.8 (C-20), 69.4
(C-30); 73.5 (C-40), 75.9 (C-50), 83.8 (C-10), 104.8, 114.9, 121.0, 127.3, 153.7, 158.9
(C-Ar), 162.6 (C-2), 169.2, 169.8, 170.3 (4 CO).
2-(20,30,40,60-Tetra-O-acetyl-b-d-galactopyranosylmercapto)benzothiazole (13d).
From 1a (0.84 g, 5.0 mmol) and 12 (2.26 g, 5.5 mmol) in the manner described for
13a. The product was purified by flash chromatography (eluent: EtOAc=pet. ether
40–60ꢀC 10–30%) to afford 13d (2.25 g, 90%) as a colorless oil (lit.[34] mp 110–
1
111ꢀC, 73%). MS; m=z: 497 (Mþ). H-NMR (CDCl3): d 2.00, 2.01, 2.07, 2.18 (4s,
12H, 4 Ac), 3.88 (s, 3H, OCH3), 4.07–4.19 (m, 3H, 50-H, 6-H0, 600-H), 5.23 (dd,
J ¼ 3.4, 9.8 Hz, 1H, 40-H), 5.44 (dd, J ¼ 9.9, 10.1 Hz, 1H, 20-H), 5.52 (d, J ¼ 3.3 Hz,
1H, 30-H), 5.56 (d, J ¼ 10.1 Hz, 1H, 10-H), 7.34–7.95 (m, 4H, Ar-H). 13C-NMR
(CDCl3): d 20.3, 20.4, 20.4, 20.4 (4 Ac), 61.1 (C-60), 67.7 (C-20), 69.9 (C-30), 71.4
(C-40), 74.7 (C-50), 84.24 (C-10), 120.8, 122.0, 124.8, 126.1, 135.5, 152.4 (C-Ar),
161.9 (C-2), 169.3, 169.6, 169.9, 170.0 (4 CO).
2-(20,30,40,60-Tetra-O-acetyl-b-d-galactopyranosylmercapto) benzoxazole (13e) and
3-(20,30,40,60-Tetra-O-acetyl-b-d-galactopyranosyl)-2-thiobenzoxazole (14b). From
1b (0.76 g, 5.0 mmol) of 1b and 12 (2.26 g, 5.5 mmol) in the manner described for
13a and 14a. Yield 1.09 g (45%) of 13e as pale yellow foam and 0.92 g (38%) of
14b as pale yellow oil.

Benzothiazole and Benzoxazole Nucleosides
2071
13e: MS; m=z: 481 (Mþ). Calculated for C21H23NO10S (481.47): C, 52.39; H,
1
4.81; N, 2.91. Found: C, 52.20; H, 4.96; N, 2.68. [a]D þ 11.5ꢀ (c 0.7, CHCl3). H-
NMR (CDCl3): d 1.98, 2.02, 2.08, 2.19 (4s, 12H, 4 Ac), 4.14–4.29 (m, 3H, 5-H0,
60-H, 600-H), 5.22 (dd, J ¼ 3.4, 9.9 Hz, 1H, 40-H), 5.30 (dd, J ¼ 10.1, 10.1 Hz, 1H,
20-H), 5.44 (dd, J ¼ 3.4, 10.0 Hz, 1H, H-30), 5.72 (d, J ¼ 10.2 Hz, 1H, 10-H), 7.20–
7.70 (m, 4H, Ar-H). 13C-NMR (CDCl3): d 20.5, 20.6, 20.6, 20.7 (4 Ac), 61.2 (C-
60), 67.0 (C-20), 67.1 (C-30), 71.7 (C-40), 75.0 (C-50), 83.9 (C-10), 110.2, 118.9, 124.7,
125.9, 141.5, 151.9 (C-Ar), 161.0 (C-2), 169.7, 169.9, 170.2, 170.4 (4 CO).
14b: MS; m=z: 481 (Mþ). Calculated for C21H23NO10S (481.47): C, 52.39; H,
1
4.81; N, 2.91. Found: C, 52.28; H, 4.94; N, 2.72. H-NMR (CDCl3): d 2.00, 2.03,
2.07, 2.22 (4s, 12H, 4 Ac), 4.16–4.30 (m, 3H, 50-H, 60-H, 600-H), 5.24 (dd, J ¼ 9.6,
10.1 Hz, 1H, 40-H), 5.38 (dd, J ¼ 9.2, 9.5 Hz, 1H, 20-H), 5.63 (dd, J ¼ 9.4, 9.4 Hz,
1H, 30-H), 6.32 (d, J ¼ 9.1 Hz, 1H, 10-H), 7.20–7.50 (m, 4H, Ar-H).
5-Methoxy-2-(20,30,40,60-tetra-O-acetyl-b-d-galactopyranosylmercapto)benzothia-
zole (13f) and 5-Methoxy-3-(20,30,40,60-tetra-O-acetyl-b-d-galactopyranosyl)-2-thio-
benzothiazole (14c). From 1c (1.15 g, 5.0 mmol) and 12 (2.26 g, 5.5 mmol) in the
manner described for 13a and 14a. Yield 1.60 g (60%) of 13f as pale yellow foam
and 0.58 g (22%) of 14c as pale yellow foam.
13f: MS; m=z: 527 (Mþ). Calculated for C22H25NO10S2 (527.56): C, 50.09; H,
1
4.78; N, 2.66. Found: C, 50.26; H, 5.16; N, 2.52. H-NMR (CDCl3): d 1.98, 2.02,
2.08, 2.19 (4s, 12H, 4 Ac), 3.82 (s, 3H, OCH3), 4.12–4.32 (m, 3H, 5-H0, 60-H, 600-H),
5.22 (dd, J ¼ 3.4, 9.8 Hz, 1H, 40-H), 5.30 (dd, J ¼ 10.1, 10.1 Hz, 1H, 20-H), 5.45
(d, J ¼ 3.4 Hz, 1H, H-30), 5.74 (d, J ¼ 10.2 Hz, 1H, 10-H), 7.15–7.65 (m, 3H, Ar-H).
14c: MS; m=z: 527 (Mþ). Calculated for C22H25NO10S2 (527.56): C, 50.09; H,
1
4.78; N, 2.66. Found: C, 49.92; H, 5.10; N, 2.94. H-NMR (CDCl3): d 2.00, 2.03,
2.07, 2.22 (4s, 12H, 4 Ac), 3.86 s, 3H, OCH3), 4.20–4.36 (m, 3H, 50-H, 60-H, 600-H),
5.24 (dd, J ¼ 9.6, 10.2 Hz, 1H, 40-H), 5.38 (dd, J ¼ 9.3, 9.5 Hz, 1H, 20-H), 5.64 (dd,
J ¼ 9.4, 9.4 Hz, 1H, 30-H), 6.33 (d, J ¼ 9.1 Hz, 1H, 10-H), 7.05–7.53 (m, 3H, Ar-H).
2-(b-d-Glucopyranosylmercapto)benzothiazole (15a). From 13a (0.50 g, 1.0 mmol)
of 13a in the manner described for 5a. The product was chromatographed on silica
gel using MeOH, in gradient, (0–10%) and CH2Cl2, as eluent to give 15a (0.28 g,
1
86%) as a white foam (lit.,[32] mp 110–180ꢀC, 75%). MS; m=z: 329 (Mþ). H-NMR
(CD3OD-d4): d 3.17–3.36 (m, 4H, 40-H, 50-H, 60-H, 600-H), 3.60 (dd, J ¼ 4.3, 9.3 Hz,
1H, 20-H), 3.78 (dd, J ¼ 1.6, 12.0 Hz, 1H, 30-H), 5.57 (d, 1H, J ¼ 9.1 Hz, 10-H); 7.20–
7.78 (m, 4H, Ar-H).
2-(b-d-Glucopyranosylmercapto)benzoxazole (15b). From 13b (0.73 g, 1.0 mmol)
of 13b in the manner described for 5a. Yield 0.25 g (80%) as white foam. MS; m=z: 313
(Mþ). Calculated for C13H15NO6S (313.32): C, 49.83; H, 4.82; N, 4.47. Found: C,
1
49.59; H, 4.98; N, 4.60. [a]D ꢁ106ꢀ (c 0.5, MeOH). H-NMR (CD3OD-d4): d 3.15–
3.36 (m, 4H, 40-H, 50-H, 60-H, 600-H), 3.60 (dd, J ¼ 4.2, 9.4 Hz, 1H, 20-H), 3.78 (dd,
J ¼ 1.6, 12.1 Hz, 1H, 30-H), 5.57 (d, J ¼ 9.4 Hz, 1H, 10-H), 7.00–8.00 (m, 4H, Ar-H).
5-Methoxy-2-(b-d-glucopyranosylmercapto)benzothiazole (15c). From 13c
(0.53 g, 1.0 mmol) in the manner described for 5a. Yield 0.30 g (84%) as a white solid,

2072
Khodair, Al-Masoudi, and Gesson
mp 127–129ꢀC. MS; m=z: 359 (Mþ). Calculated for C14H17NO6S2 (359.41): C, 46.79;
1
H, 4.77; N, 3.90. Found: C, 46.43; H, 4.60; N, 4.04. [a]D ꢁ87ꢀ (c 0.23, MeOH). H-
NMR (CD3OD-d4): d 3.32 (s, 3H, OCH3), 3.50 (m, 5H, 20-H, 40-H, 50-H, 60-H, 600-H),
3.77 (dd, J ¼ 4.0, 12.2 Hz, 1H, 30-H), 5.18 (d, 1H, J ¼ 9.2 Hz, 10-H), 6.94–7.68 (m, 3H,
13
Ar-H). C-NMR (CD3OD-d4): d 55.5 (OCH3), 61.5 (C-60), 69.8 (C-20), 72.5 (C-30),
78.3 (C-40), 80.9 (C-50), 86. 6 (C-10), 104.7, 114.1, 121.2, 127.0, 153.9, 158.8 (C-Ar),
165.5 (C-2).
2-(b-d-Galactopyranosylmercapto)benzothiazole (15d). From 13d (0.50 g,
1.0 mmol) in the manner described for 5a. Yield 0.28 g (85%)þas a white solid, mp
118–120ꢀC (lit.,[32] mp 100–195ꢀC, 79%). MS; m=z: 329 (M ). [a]D þ 5.0ꢀ (c 0.7,
1
MeOH). H-NMR (DMSO-d6): d 3.37–3.80 (m, 6H, 20-H, 30-H, 40-H, 50-H, 60-H,
600-H), 4.64 (d, 1H, J ¼ 4.6 Hz, 60-OH), 4.70 (d, 1H, J ¼ 5.2 Hz, 40-OH), 5.05
13
(d, 1H, J ¼ 5.5 Hz, 30-OH), 5.10 (d, 1H, J ¼ 9.7 Hz, 10-H), 5.50 (d, 1H, J ¼ 6.0 Hz,
20-OH), 7.37–8.04 (m, 4H, Ar-H). C-NMR (DMSO-d6): d 60.3 (C-60), 68.4 (C-20),
69.6 (C-30), 74.7 (C-40), 79.9 (C-50), 87.2 (C-10), 121.5, 121.8, 124.7, 126.5, 135.2,
152.5 (C-Ar), 165.4 (C-2).
2-(b-d-Galactopyranosylmercapto)benzoxazole (15e). From 13e (0.48 g,
1.0 mmol) in the manner described for 5a. Yield 0.26 g (84%) as pale yellow foam.
MS; m=z: 313 (Mþ). Calculated for C13H15NO6S (313.33): C, 49.83; H, 4.82; N,
4.47. Found: C, 49.62; H, 5.00; N, 4.56. [a]D ꢁ71ꢀ (c 0.4, MeOH). 1H-NMR
(DMSO-d6): d 3.35–3.76 (m, 6H, 20-H, 30-H, 40-H, 50-H, 60-H, 600-H), 4.62 (d,
J ¼ 5.0 Hz, 1H, 60-OH), 4.65 (d, J ¼ 5.8 Hz, 1H, 40-OH), 5.06 (d, J ¼ 5.6 Hz, 1H,
30-OH), 5.36 (d, J ¼ 9.8 Hz, 1H, 10-H), 5.53 (d, J ¼ 6.2 Hz, 1H, 20-OH), 7.33–7.68
13
(m, 4H, Ar-H). C-NMR (DMSO-d6): d 60.1 (C-60), 68.12 (C-20), 69.3 (C-30), 74.3
(C-40), 79.8 (C-50), 9.70 (C-10), 110.2, 118.3, 124.5, 124.6, 141.1, 151.2 (C-Ar),
162.5 (C-2).
5-Methoxy-2-(b-d-galactopyranosylmercapto)benzothiazole (15f). From 13f
(0.53 g, 1.0 mmol) in the manner described for 5a. Yield 0.29 g (80%) as pale yellow
foam. MS; m=z: 359 (Mþ). Calculated for C14H17NO6S2 (359.41): C, 46.79; H, 4.77;
1
N, 3.90. Found: C, 46.50; H, 4.94; N, 3.58. [a]D ꢁ20ꢀ (c 0.2, MeOH). H-NMR
(DMSO-d6): d 3.30–3.83 (m, 9H, OCH3, 20-H, 30-H, 40-H, 50-H, 60-H, 600-H), 4.59–
4.68 (m, 2H, 40-OH, 60-OH), 5.00 (d, 1H, J ¼ 5.4 Hz, 30-OH), 5.08 (d, 1H, J ¼ 9.7 Hz,
Hz, 10-H), 5.45 (d, 1H, J ¼ 6.1 Hz, 20-OH), 6.99–7.90 (m, 3H, Ar-H).
3-(b-d-Galactopyranosyl)-2-thiobenzoxazole (16a). From 14b (0.48 g, 1.0 mmol)
in the manner described for 5a. Yield 0.26 g (83%) of 16a as pale yellow foam.
MS; m=z: 313 (Mþ). Calculated for C13H15NO6S (313.33): C, 49.83; H, 4.83; N,
4.47. Found: C, 49.72; H, 4.98; N, 4.18. [a]D þ 56ꢀ (c 0.4, MeOH). 1H-NMR
(CD3COCD3-d6): d 3.82–3.91 (m, 4H, 40-H, 50-H, 60-H, 600-H), 4.05 (br. s, 1H, 60-
OH), 4.14 (m, 1H, 30-H), 4.39–4.45 (m, 2H, 30-OH, 40-OH), 4.48 (d, J ¼ 9.5 Hz,
1H, 20-H), 4.72 (d, J ¼ 3.8 Hz, 1H, 20-OH), 6.00 (d, J ¼ 9.1 Hz, 1H, H-10), 7.31–
13
7.73 (m, 4H, Ar-H). C-NMR (DMSO-d6): d 62.4 (C-60), 69.2 (C-20), 69.9 (C-30),
74.8 (C-40), 78.9 (C-50), 88.4 (C-10), 110.7, 113.5, 125.13, 125.7, 140.8, 147.8 (C-
Ar), 181.4 (C-2).

Benzothiazole and Benzoxazole Nucleosides
2073
14c
5-Methoxy-3-(b-d-galactopyranosyl)-2-thiobenzothiazole
(16b). From
(0.53 g, 1.0 mmol) in the manner described for 5a. Yield 0.28 g (77%) as pale yellow
foam. MS; m=z: 359 (Mþ). Calculated for C14H17NO6S2 (359.41): C, 46.79; H,
4.77; N, 3.90. Found: C, 46.46; H, 4.88; N, 3.80. [a]D þ 15ꢀ (c 0.2, MeOH).
1H-NMR (CD3COCD3-d6): d 3.83 (s, 3H, OCH3), 4.03–4.53 (m, 5H, 30-H, 40-H,
50-H, 60-H, 600-H), 4.63 (dd, J ¼ 8.8, 9.5 Hz, 1H, 20-H), 6.60 (d, J ¼ 9.2 Hz, 1H,
H-10), 6.91–7.90 (m, 3H, Ar-H).
2-(20,30,40,60-Tetra-O-acetyl-b-d-glucopyranosylmercapto)pyridine (18a). From
17 (0.55 g, 5.0 mmol) in the manner described for 13a. The product was purified
by flash chromatography using CH2Cl2 as eluent to afford 18a (1.70 g, 77%) as pale
1
yellow solid, mp 140–142ꢀC (lit.,[35] mp 120–123ꢀC, 72%). MS; m=z: 441 (Mþ). H-
NMR (CDCl3): d 2.01, 2.02, 2.03,2.04 (4s, 12H, 4 Ac), 3.88 (m, 1H, 50-H), 4.12 (dd,
J ¼ 2.2, 12.3 Hz, 1H, 60-H), 4.25 (dd, J ¼ 4.7, 12.4 Hz, 1H, 600-H), 5.16 (d, J ¼ 9.9 Hz,
1H, 40-H), 5.25 (d, J ¼ 10.2 Hz, 1H, 20-H), 5.35 (dd, J ¼ 9.3, 9.3 Hz, 1H, 30-H), 5.84
(d, J ¼ 10.4 Hz, 1H, H-10), 7.05–8.46 (m, 4H, Ar-H). 13C-NMR (CDCl3): d 20.6, 20.6,
20.7, 20.7 (4 Ac), 62.0 (C-60) 68.3 (C-20), 69.5 (C-30), 74.2 (C-40), 75.9 (C-50), 81.6
(C-10), 120.90, 123.3, 136.6, 149.7, 155.3 (C-Ar), 169.4, 169.5, 170.2, 170.6 (4 CO).
2-(20,30,40,60-Tetra-O-acetyl-b-d-galactopyranosylmercapto)pyridine (18b). From
17 (0.55 g, 5.0 mmol) and 12 (2.26 g, 5.5 mmol) in the manner described for 13a.
The product was purified by flash chromatography (eluent, CH2Cl2) to afford
18b (1.90 g, 86%) as pale yellow foam (lit.,[35] syrup, 85%). MS; m=z: 441 (Mþ).
1H-NMR (CDCl3): d 1.98, 2.02, 2.15, 2.22 (4s, 12H, 4 Ac), 4.10–4.17 (m, 3H,
50-H, 60-H, 600-H), 5.22 (dd, J ¼ 3.4, 9.9 Hz, 1H, 40-H), 5.40 (d, J ¼ 10.2 Hz, 1H,
20-H), 5.50 (d, J ¼ 3.4 Hz, 1H, 30-H), 5.84 (d, J ¼ 10.4 Hz, 1H, 10-H), 7.09–8.47
13
(m, 4H, Ar-H). C-NMR (CDCl3): d 20.3, 20.3, 20.4, 20.5 (4 Ac), 61.1 (C-60),
66.5 (C-20), 67.2 (C-30), 71.7 (C-40), 74.2 (C-50), 81.8 (C-10), 120.7, 123.1, 136.6,
149.2, 155.1 (C-Ar), 169.4, 169.7, 169.9, 170.0 (4 CO).
2-(b-d-Glucopyranosylmercapto)pyridine (19a). From 18a (0.55 g, 1.0 mmol) in
the manner described for 15a. The product was chromatographed on silica gel using
MeOH, in gradient, (0–5%) and CH2Cl2 as eluent to give 19a (0.27 g, 97%) as a white
foam (lit.,[37] mp 93–101ꢀC, 75%). MS; m=z: 273 (Mþ). 1H-NMR (CD3OD-d4):
d 3.27–3.41 (m, 4H, 40-H, 50-H, 60-H, 600-H), 3.60 (m, 1H, 30-H), 3.76 (m, 1H, 20-H),
5.12(d, J ¼ 9.8 Hz, 1H, 10-H), 7.04–8.29 (m, 4H, Ar-H). 13C-NMR (DMSO-d6):
d 62.6 (C-60), 71.1 (C-20), 73.7 (C-30), 79.5 (C-40), 82.0 (C-50), 86.1 (C-10), 122.0,
124.5, 138.7, 150.1 (C-Ar), 159.1 (C-2).
2-(b-d-Galactopyranosylmercapto)pyridine (19b). From 18b (0.50 g, 1.0 mmol)
in the manner described fþor 5a. Yield 257 mg (85%) as a yellow solid, mp 162–
164ꢀC. MS; m=z: 273 (M ). Calculated for C11H15NO5S (273.30): C, 48.34; H,
1
5.53; N, 5.13. Found: C, 48.00; H, 5.68; N, 4.82. [a]D ꢁ38ꢀC (c 0.5, MeOH). H-
NMR (DMSO-d6): d 3.15–3.74 (m, 6H, 20-H, 30-H, 40-H, 50-H, 60-H, 600-H), 4.54–
4.63 (m, 2H, 40-OH, 60-OH), 4.93 (d, J ¼ 5.6 Hz, 1H, 20-OH), 5.07 (d, J ¼ 9.7 Hz,
1H, 10-H), 5.24 (d, J ¼ 5.8 Hz, 1H, 20-OH), 7.11–8.37 (m, 4H, Ar-H). 13C-NMR

2074
Khodair, Al-Masoudi, and Gesson
(DMSO-d6): d 60. 7 (C-60), 68.6 (C-20), 69.2 (C-30), 75.0 (C-40), 79.9 (C-50), 84.8 (C-
10), 120.46, 122.1, 137.2, 149.37 (C-Ar), 158.8 (C-2).
2-(20,30,50-Tri-O-acetyl-b-d-ribofuranosylmercapto)pyridine
(21). From
17
(0.55 g, 5.0 mmol) in the manner described for 4a. The product was purified by flash
chromatography (eluent: EtOAc=pet. ether, 40–60ꢀC, 10–30%,) to give 21 (1.77 g,
1
96%) as a yellow oil (lit.,[36] syrup, 95%). MS; m=z: 369 (Mþ). H-NMR (CDCl3): d
1.97, 1.98, 1.99 (3s, 9H, 3 Ac), 4.03 (dd, J ¼ 5.0, 12.9 Hz, 1H, 50-H), 4.27 (m, 2H, 40-
H, 500-H), 5.32 (dd, J ¼ 5.0, 5.0 Hz, 1H, 30-H), 5.39 (dd, J ¼ 4.7, 5.0 Hz, 1H, 20-H),
6.09 (d, J ¼ 4.6 Hz, 1H, 10-H.), 6.93–8.34 (m, 4H, Ar-H). 13C-NMR (CDCl3): d 20.5,
20. 8, 22.5 (3 Ac), 63.2 (C-50), 71.4 (C-30), 74.5 (C-20), 80.1 (C-40), 84.9 (C-10), 120.7
(C-4), 123.1 (C-5), 136.7 (C-3), 149.7 (C-6), 156.2 (C-2), 169.5, 169.7, 170.4 (3 CO).
2-(b-d-Ribofuranosylmercapto)pyridine (22). From 21 (0.74 g, 2.0 mmol) in the
manner described for 5a. The product was chromatographed on silica gel using
MeOH, in gradient, (0–5%) and CH2Cl2þas eluent to give 22 (0.44 g, 90%) as a yellow
solid, mp 136–138ꢀC. MS; m=z: 243 (M ). Calculated for C10H13NO4S (243.27): C,
49.37; H, 5.38; N, 5.76. Found: C, 49.15; H, 5.62; N, 5.70. 243 (Mþ). [a]D þ 44ꢀ
1
(c 2.0, MeOH). H-NMR (DMSO-d6): d 3.50 (m, 2H, 50-H, 500-H), 3.90 (m, 1H, 40-
H), 4.02 (m, 2H, 20-H, 30-H), 4.70 (t, J ¼ 5.6 Hz, 1H, 50-OH), 4.96 (d, J ¼ 5.3 Hz,
13
1H, 30-OH), 5.34 (d, J ¼ 5.5 Hz, 1H, 20-OH), 5.80 (d, J ¼ 4.6 Hz, 1H, 10-H), 7.09–
8.42 (m, 4H, Ar-H). C-NMR (DMSO-d6): d 62.1 (C-50), 71.0 (C-30), 75.2 (C-20),
85.5 (C-40), 86.8 (C-10) 120.2 (C-4), 122.5 (C-5), 136.8 (C-3), 149.3 (C-6), 158.13 (C-2).
ACKNOWLEDGMENTS
We thank ADIR (Groupe Servier, Paris) for carrying out the antitumor testing
of the deprotected nucleosides. A. I. K. is grateful for an Alexander von Humboldt
Fellowship.
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Received January 15, 2003
Accepted August 20, 2003