An Efficient Route to Pyrimidine Nucleoside Analogues by [4 + 2] Cycloaddition Reaction

Article abstract of DOI:10.1021/jo034709a

We report here an efficient synthesis for pyrimidine nucleoside analogues by [4 + 2] cycloaddition reaction. These compounds were obtained by convergent chemistry from glycosyl isothiocyanates 3a-f (pyranoses, furanoses, and dissaccharides) and diazadienium salt 5. In fact, diazapentadienium iodide 5 prepared from vinylthioamide 4 is an efficient intermediate in heterocyclic synthesis and reacts with isothiocyanates 3a-f affording β-D-uracil analogues 7a-f in good yields and with total regiocontrol. All compounds were fully characterized by IR, HRMS, and ¹³C and ¹H NMR (COSY and HMQC).

Full text of DOI:10.1021/jo034709a

An Efficien t Rou te to P yr im id in e Nu cleosid e An a logu es by [4 + 2]
Cycloa d d ition Rea ction
Morwenna S. M. Pearson,† Ae´lig Robin,† Nathalie Bourgougnon,‡ J ean Claude Meslin,† and
David Deniaud*,†
Laboratoire de Synthe`se Organique, UMR CNRS 6513, Faculte´ des Sciences et des Techniques, 2,
Rue de la Houssinie`re 44322 Nantes Cedex 03, France, and Laboratoire de Biologie Mole´culaires EA
2594, Centre de recherche et d’enseignemant Yves Coppens, Campus de Tohannic, BP 573,
56017 Vannes, France
david.deniaud@chimie.univ-nantes.fr
Received May 26, 2003
We report here an efficient synthesis for pyrimidine nucleoside analogues by [4 + 2] cycloaddition
reaction. These compounds were obtained by convergent chemistry from glycosyl isothiocyanates
3a -f (pyranoses, furanoses, and dissaccharides) and diazadienium salt 5. In fact, diazapentadienium
iodide 5 prepared from vinylthioamide 4 is an efficient intermediate in heterocyclic synthesis and
reacts with isothiocyanates 3a -f affording â-D-uracil analogues 7a -f in good yields and with total
1
regiocontrol. All compounds were fully characterized by IR, HRMS, and 13C and H NMR (COSY
and HMQC).
In tr od u ction
lecular transposition process were investigated in order
to improve the synthesis of nucleoside pyrimidinone
analogues.8 Significant and diverse pharmaceutical val-
ues of various nucleosides have inspired investigations
toward the development of new synthetic methods for
their practical preparation.
Among the N-glycosides, glycosyl isothiocyanates are
attracting much attention because of the synthetic flex-
ibility of the isothiocyanate function.9 In fact, sugar
isothiocyanates play a key role in the preparation of a
variety of functional groups as well as in the construction
of heterocyclic ring systems. In particular, they have been
used for the synthesis of a wide spectrum of carbohydrate
derivatives with thiourea structure.10 Recently, glycosyl
isothiocyanates were used to prepare galactofuranosidase
inhibitors,11 â-amphiphilic compounds,12 hydantocidin,13
spironucleosides,14 and glycodendrimers.15 Paradoxically,
only few syntheses of nucleoside analogues by [4 + 2]
For many years, modified nucleosides have been widely
used as antiviral and antitumor agents.1 Considerable
efforts have been undertaken to exploit synthetic routes
to these compounds.2 In the course of the preparation of
nucleosides, base moieties are generally introduced by
substitution or more rarely by construction.3 Convention-
ally, synthesis of N-linked oligosaccharides has been
achieved by coupling of activated glycosyl derivatives
with heterocyclic nucleobase analogues such as pyrimi-
dinones.4 Alternative methods for N-alkylation include
heating with trimethyl phosphate5 and alkylation of
O-silylated derivatives,6 which is an important method
for unambiguous N-alkylation especially ribosylation of
uracils.7 Complementary studies through an intramo-
† Universite´ de Nantes.
‡ Universite´ de Bretagne Sud.
(1) (a) Garg, R.; Gupta, S.; Gao, H.; Babu, M.; Debnath, A.; Hansch,
C. Chem. Rev. 1999, 99, 3523. (b) Hurin, D. N.; Okabe, M. Chem. Rev.
1992, 92, 1745. (c) Lin, T. S.; Luo, M. Z.; Liu, M. C.; Zhu, Y. L.; Gullen,
E.; Dutschman, G. E.; Cheng, Y. C. J . Med. Chem. 1996, 39, 1757. (d)
Webb, T. R.; Mitsuya, H.; Broder, S. J . Med. Chem. 1988, 31, 1475
and references therein.
(2) (a) Zorbach, W. W. Synthesis 1970, 7, 329. (b) Kahne, D.; Walker,
S.; Cheng, Y.; Van Engen, D. J . Am. Chem. Soc. 1989, 111, 6881. (c)
Ichikawa, E.; Kato, K. Curr. Med. Chem. 2001, 8, 385. (d) Komatsu,
H.; Araki, T. Tetrahedron Lett. 2003, 44, 2899. (e) Trelles, J . A.;
Fernandez, M.; Lewkowicz, E. S.; Iribarren, A. M.; Sinisterra, J . V.
Tetrahedron Lett. 2003, 44, 2605.
(7) Matsuda, A.; Kurasawa, Y.; Watanabe, K. Synthesis 1981, 9, 748.
(8) (a) J ung, M. E.; Castro, C. J . Org. Chem. 1993, 58, 507. (b) Sujino,
K.; Sugimura, H. Chem. Lett. 1993, 1187. (c) Lipshutz, B. H.; Stevens,
K. L.; Lowe, R. F. Tetrahedron Lett. 1995, 36, 2711. (d) Xia, X.; Wang,
J .; Hager M. W.; Sisti, N.; Liotta, D. C. Tetrahedron Lett. 1997, 38,
1111. (e) Sugimura, H.; Katoh, Y. Chem. Lett. 1999, 361.
(9) (a) Mukerjee, A. K.; Ashare, R. Chem. Rev. 1991, 91, 1. (b) Al
Massoudi, N.; Hassan, N. A.; Al-Soud, Y. A.; Schmidt, P.; Gaafar, A.
E.-D.; Weng, M.; Marino, S.; Schoch, A.; Amer, A.; J ochins, J . C. J .
Chem. Soc., Perkin Trans. 1 1998, 5, 947.
(3) Ane´, A.; Prestat, G.; Manh, G. T.; J osse, S.; Pipelier, M.; Lebreton,
J .; Prade`re, J . P.; Dubreuil, D. Pure Appl. Chem. 2001, 73, 1189.
(4) (a) Plimil, J .; Prystas, M. Adv. Heterocycl. Chem. 1967, 8, 115.
(b) Niedballa, U.; Vorbruggen, H. J . Org. Chem. 1974, 39, 3672. (c)
Vorbruggen, H.; Krolikiewicz, K.; Bennua, B. Chem. Ber. 1981, 114,
1234. (d) Vorbruggen, H.; Hofle, G. Chem. Ber. 1981, 114, 1256. (e)
Sugimura, H.; Muramoto, I.; Nakamura, T.; Osumi, K. Chem. Lett.
1993, 169. (f) J ungmann, O.; Pfleiderer, W. Tetrahedron Lett. 1996,
37, 8355.
(10) Saleh, M. A. Nucleosides, Nucleotides Nucleic Acids 2002, 21,
401. (b) Benito, J . M.; Ortiz Mellet, C.; Sadalapure, K.; Lindhorst, T.
K.; Defaye, J .; Garcia Ferna´ndez, J . M. Carbohydr. Res. 1999, 320,
37. (c) D´ıaz Pe´rez, V. M.; Ortiz Mellet, C.; Fuentes, J .; Garcia
Ferna´ndez, J . M. Carbohydr. Res. 2000, 326, 161. (d) Fuentes, J .;
Moreda, W.; Ortiz, C.; Robina, I.; Welsh, C. Tetrahedron 1992, 48, 6413.
(11) Marino, C.; Herczegh, P.; de Lederkremer, R. M. Carbohydr.
Res. 2001, 333, 123.
(12) Prata, C.; Mora, N.; Polidori, A.; Lacombe, J .-M.; Pucci, B.
Carbohydr. Res. 1999, 321, 15.
(13) (a) Shiozaki, M. Carbohydr. Res. 2001, 335, 147. (b) Shiozaki,
M. Carbohydr. Res. 2002, 337, 2077.
(5) Yamauchi, M.; Kinoshita, M. J . Chem. Soc., Perkin Trans. 1
1973, 8, 391.
(6) Mu¨ller, C. E. Tetrahedron Lett. 1991, 32, 6539.
10.1021/jo034709a CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/01/2003
J . Org. Chem. 2003, 68, 8583-8587
8583

Pearson et al.
SCHEME 1. Syn th etic Rou te to Nu cleosid es 7a -f
in the presence of molecular sieves (4 Å) afforded the
desired N-glycosides 3a -f (Scheme 2) without yielding
corresponding thiocyanates.21,22 The reaction is totally
diastereoselective affording only the 1,2-trans-isothiocy-
anates, probably due to the anchimeric participation of
the vicinal 2-O-acyl group.21a,23 The anomeric configura-
tion could be easily determined by measuring the ano-
meric coupling constant J 1,2. The J 1,2 value (∼8.4 Hz)
indicated pyranoses 3a -d to be â. The â-D-furanose
configuration of 3e,f was equally established by means
of H1-H2 coupling constant values, which being smaller
than 1 Hz indicate a 1,2-trans relationship.24 Compounds
2e,f were reacted directly with an excess of potassium
thiocyanate without purification. In fact, 2,3,5-tri-O-
benzoyl-D-ribofuranosyl bromide 2e and 2,3,5-tri-O-ben-
zoyl-D-xylofuranosyl bromide 2f proved extremely un-
stable and degraded on silica gel during chromatography.
Rajappa and Advani have previously reported the
condensation of N,N-dimethylformamide dimethyl acetal
and thioacetamide to furnish vinylthioamide 4 in very
poor yields (6.5%).25 An alternative preparation consisting
of sulfhydratation of the commercially available 3-dim-
ethylaminoacrylonitrile (trans/cis ratio: 95/5) in the pres-
ence of triethylamine and pyridine permitted the isola-
tion of compound 4 in more satisfactory yields (79%), and
with exclusive E configuration (Scheme 3).
During the past years, different types of 2-amino-1-
thiazabutadienes have been studied in our laboratory.
We have reported that these compounds could react
either as thiazadienes or diazadienes giving rise to
tetrahydropyrimidines or 1,3-thiazines.18a,26 Vinylthioa-
mide 4 can have also two tautomeric forms either
azadiene or thiadiene, and thus probably possess a wide
reactivity. With the aim to investigate the synthesis of
uracil analogues, we have rigidified the structure by
alkylation of compound 4 to obtain only the azadiene
chain. Alkylation of vinylthioamide afforded, as the sole
product, the corresponding S-methyl salt 5, due to the
higher nucleophilicity of the sulfur. In contrast to the
method developed in the literature, we never observed a
dehydrohalogenation of iodide 5 in the basic medium to
afford methylthioimine.26a,27 In this case, the expected
product was not stable enough to be isolated (Scheme 3).
This problem was solved by the use of the cationic form.
In fact, the reaction of diazadienium iodide 5 in a [4 + 2]
cycloaddition reaction with glycosyl isothiocyanates 3a -f
afforded methylsulfanyldihydropyrimidinethiones 7a -f
in good yields (Table 1). In this reaction, the intermediate
6 was never isolated and the final step consisted in a
cycloaddition or addition-cyclization reactions of glycosyl
isothiocyanates have been described.14a,16 Therefore, it
would be interesting to establish simple synthetic ap-
proaches and novel concepts in the synthesis and devel-
opment of pyrimidine nucleoside analogues.
During the last years, we have focused our research
on the development of efficient methodologies to build
heterocyclic compounds.17 In our previous paper, we
described the versatility of cationic dienes as stable
synthons for the preparation of various heterocyclic
rings.18 We report here the reactivity of diazadienium
iodide 5 in a [4 + 2] cycloaddition reaction with glycosyl
isothiocyanates 3a -f affording sugar pyrimidines 7a -f
(Scheme 1).19 This type of derivatives opens a new route
to original functionalized six-membered ring heterocycles
with strong biological potential.
Resu lts a n d Discu ssion
Starting glycosyl isothiocyanates 3a -f were obtained
in two steps in good to moderate overall yields. Thus,
acetylated (for 3a -d ) or benzoylated (for 3e,f) glycosyl
bromides were prepared by stirring the respective ac-
etates in HBr-acetic acid solution.20 A subsequent step
in a phase-transfer reaction using thiocyanate anion and
tetrabutylammonium bromide as catalyst in acetonitrile
(14) (a) Fuentes, J .; Molina, J . L.; Pradera, M. A. Tetrahedron:
Asymmetry 1998, 9, 2517. (b) Gasch, C.; Pradera, M. A.; Salameh, B.
A. B.; Molina, J . L.; Fuentes, J . Tetrahedron: Asymmetry 2001, 12,
1267. (c) Gasch, C.; Salameh, B. A. B.; Pradera, M. A.; Fuentes, J .
Tetrahedron Lett. 2001, 42, 8615.
(15) (a) Andre´, S.; Pieters, R. J .; Vrasidas, I.; Kaltner, H.; Kuwabara,
I.; Liu, F.-T.; Liskamp, R. M. J .; Gabius, H.-J . ChemBioChem 2001, 2,
822. (b) Vrasidas, I.; de Mol, N. J .; Liskamp, R. M. J .; Pieters, R. J .
Eur. J . Org. Chem. 2001, 4685.
(16) (a) Takahashi, H.; Nimura, N.; Ogura, H. Chem. Pharm. Bull.
1979, 27, 1143. (b) Valent´ıny, M.; Martvon, A.; Kova´c, P. Collect. Czech.
Chem. Commun. 1981, 46, 2197. (c) Ogura, H.; Takahashi, H.; Sato,
O. Chem. Pharm. Bull. 1981, 29, 1838.
(17) (a) Charrier, J . D.; Landreau, C.; Deniaud, D.; Reliquet, A.;
Reliquet, F.; Meslin, J . C. Tetrahedron 2001, 57, 4195. (b) Landreau,
C.; Deniaud, D.; Reliquet, A.; Meslin, J . C. Synthesis 2001, 13, 2015.
(c) Landreau, C.; Deniaud, D.; Reliquet, A.; Meslin, J . C. Synthesis
2002, 3, 403. (d) Landreau, C.; Deniaud, D.; Evain, M.; Reliquet, A.;
Meslin, J . C. J . Chem. Soc., Perkin Trans. 1 2002, 6, 741. (e) Landreau,
C.; Deniaud, D.; Reliquet, A.; Meslin, J . C. Phosphorus, Sulfur Silicon
2002, 177, 2651. (f) Landreau, C.; Deniaud, D.; Reliquet, A.; Meslin,
J . C. Tetrahedron Lett. 2002, 43, 4099. (g) Landreau, C.; Deniaud, D.;
Reliquet, A.; Meslin, J . C. Eur. J . Org. Chem. 2003, 3, 421. (h)
Landreau, C.; Deniaud, D.; Meslin, J . C. J . Org. Chem. 2003, 68, 4912.
(18) (a) Friot, C.; Reliquet, A.; Reliquet, F.; Meslin, J . C. Synthesis
2000, 5, 695. (b) Landreau, C.; Deniaud, D.; Reliquet, A.; Reliquet, F.;
Meslin, J . C. J . Heterocycl. Chem. 2001, 38, 93.
(19) (a) Ueda, T.; Iida, Y.; Ikeda, K.; Mizumo, Y. Chem. Pharm. Bull.
1968, 16, 1788. (b) Ueda, T.; Nishino, H. Chem. Pharm. Bull. 1969,
17, 920. (c) Bretner, M.; Felczak, K.; Dzik, J . M.; Golos, B.; Rode, W.;
Drabikowska, A.; Poznanski, J .; Krawiec, K.; Piasek, A.; Shugar, D.;
Kulikowski, T. Nucleosides Nucleotides 1997, 16, 1295.
(20) Koch, A.; Lamberth, C.; Wetterich, F.; Giese, B. J . Org. Chem.
1993, 58, 1083.
(21) (a) Camarasa, M. J .; Fernandez-Resa, P.; Garcia-Lopez, M. T.;
de las Heras, F. G.; Mendez-Castrillon, P. P.; San Felix, A. Synthesis
1984, 6, 509. (b) Kassab, R.; Fe´lix, C.; Parrot-Lopez, H.; Bonaly, R.
Tetrahedron Lett. 1997, 38, 7555.
(22) (a) Lindhorst, T. K.; Kieburg, C. Synthesis 1995, 10, 1228. (b)
Somsa´k, L.; Czifra´k, K.; Deim, T.; Szila´gyi, L.; Be´nyei, A. Tetrahedron:
Asymmetry 2001, 12, 731.
(23) Marino, C.; Varela, O.; de Lederkremer, R. M. Carbohydr. Res.
1997, 304, 257.
(24) (a) Bundle, D. R.; Lemieux, R. D. Methodol. Carbohydr. Chem.
1976, 7, 79. (b) Marino, C.; Varela, O.; de Lederkremer, R. M.
Carbohydr. Res. 1989, 190, 65. (c) de Lederkremer, R. M.; Nahmad,
V. B.; Varela, O. J . Org. Chem. 1994, 59, 690.
(25) Rajappa, S.; Advani, B. G. Indian J . Chem., Sect. B 1978, 16,
819.
(26) (a) Friot, C.; Reliquet, A.; Reliquet, F.; Meslin, J . C. Phosphorus,
Sulfur Silicon 2000, 156, 135. (b) Landreau, C.; Deniaud D.; Reliquet,
A.; Reliquet, F.; Meslin, J . C. Heterocycles 2000, 53, 2667.
(27) Mazumdar, S. N.; Mahajan, M. P. Synthesis 1990, 5, 417.
8584 J . Org. Chem., Vol. 68, No. 22, 2003

Efficient Route to Pyrimidine Nucleoside Analogues
SCHEME 2. Syn th etic Rou te to Glycosyl Isoth iocya n a tes 3a -fa
a
Reagents and conditions: (i) CH2Cl2, HBr in AcOH, 0°C, 2 h; (ii) CH3CN, KSCN, molecular sieves 4 Å, Bu4N+ Br-, reflux, 2 h.
SCHEME 3. Syn th esis of S-Meth yl Sa lt 5a
SCHEME 4. Syn th esis of N-Nu cleosid es 7a -fa
a
Reagents and conditions: (i) Et3N, pyridine, H2S, rt, 48 h; (ii)
CH3I, THF, rt, 18 h.
TABLE 1. Yield s of Com p ou n d s 7a -f a n d Selected NMR
Da ta (δ, p p m ; J , Hz))
compd
sugar
yielda (%)
H-1 (J )
C-1
a
7a
7b
7c
7d
7e
7f
glucosyl
galactosyl
cellobiosyl
lactosyl
ribosyl
84
82
82
73
72
83
7.23 (9.5)
7.21 (8.3)
7.14 (9.2)
7.28 (8.9)
7.22 (3.0)
6.79
85.7
86.2
87.0
86.4
92.0
94.2
Reagents and conditions: (i) CH2Cl2, Et3N, rt, 3 h.
in vitro activity.28 Their evaluation as antitumor agents
is in progress, and these promising results led us to
develop new N-nucleosides.
xylosyl
In summary, we have developed an effective method
for the synthesis of various pyrimidine nucleoside ana-
logues by [4 + 2] cycloaddition reaction between glycosyl
isothiocyanates and diazadienium iodide. Advantages of
the present method are: easy availability of starting
materials, good yields in the [4 + 2] cycloaddition
reaction, high diastereoselectivity and regioselectivity,
and experimental simplicity of the procedure. Substitu-
tion of methylsulfanyl group using diverse nucleophiles
is now under investigation.
a
Isolated yields. Yields of 7a -f are based on diazadienium 5.
deamination of the formed cycloadduct giving sugar
pyrimidines 7a -f (Scheme 4).
Starting from salt 5, triethylamine can be added to
remove hydriodic acid. This [4 + 2] cycloaddition reaction
occurs in a regiocontrolled manner. The structures of
compounds 7a -f were determined unequivocally by the
complementary of the 1H/13C-2D NMR techniques (COSY
and HMQC) (Table 1). The â anomeric configuration was
fully preserved, and we observed only 1,2-trans glycosidic
linkage. In this reaction, the dimethylamine generated
in the mixture reacted with a second equivalent of the
dienophile to provide glycosyl thioureas 8a -f.
Exp er im en ta l Section
2-Am in o-4-(d im eth yla m in o)-1-th ia bu ta -1,3-d ien e (4).
Hydrogen sulfide was passed at room temperature for 4 h
through a solution of 3-dimethylaminoacrylonitrile (3.84 g, 40
These types of N-nucleosides may be attracting much
attention from the viewpoint of antiviral and antitumor
drugs. Preliminary biological tests (antiviral and cyto-
toxicity assays) with pyrimidine glycoside 7a against
Herpes simplex virus type 1 (HSV-1) showed a significant
(28) Cytotoxic effect of pyrimidine glycoside 7a on the Vero cells was
not observed in the range of the concentrations tested. After 3 days of
treatment, 39% cellular destruction was observed at 200 µg/mL (CC50
> 200 µg/mL). Compound 7a is efficient against HSV-1 in vitro. 59%
cellular protection was obtained for 200 µg/mL 72 h after infection
(EC50 111.20 µg/mL).
J . Org. Chem, Vol. 68, No. 22, 2003 8585

Pearson et al.
mmol) in triethylamine (25 mL) and pyridine (25 mL). The
solvents were removed, and the residue was crystallized from
dichloromethane then methanol to provide 4 as a white solid
(4.12 g, 31.7 mmol, 79%). Mp: 189-191 °C. IR (KBr): 3342,
1605, 1344, 1116 cm-1. 1H NMR (DMSO-d6) δ: 2.88 (br s, 6H,
N(CH3)2), 5.20 (d, 1H, J ) 12.2 Hz, CHCS), 7.69 (d, 1H, J )
12.2 Hz, CHN), 7.85 (br s, 1H, NH2), 7.99 (br s, 1H, NH2). 13C
NMR (DMSO-d6) δ: 38.7 and 43.76 (N(CH3)2), 96.4 (CHCS),
155.2 (CHN), 194.6 (CS). MS: m/z 130 (M+, 100), 97 [M -
SH]+, 86 (10). Anal. Calcd for C5H10N2S: C, 46.12; H, 7.74; N,
21.51. Found: C, 46.34; H, 7.54; N, 21.74.
low crystals (yield 82%). Mp: 124-126 °C. IR (KBr): 1750,
1613, 1493, 1228 cm-1 1H NMR (CDCl3) δ: 1.99 (s, 3H,
.
COCH3), 2.00 (s, 3H, COCH3), 2.01 (s, 3H, COCH3), 2.03 (s,
3H, COCH3), 2.04 (s, 3H, COCH3), 2.10 (s, 3H, COCH3), 2.12
(s, 3H, COCH3), 2.60 (s, 3H, CH3S), 3.68 (ddd, 1H, J ) 9.4,
4.5, 2.2 Hz, glu H5′), 3.85 (dd, 1H, J ) 10.3, 9.2 Hz, glu H4),
3.93 (ddd, 1H, J ) 10.3, 5.5, 1.6 Hz, glu H5), 4.04 (dd, 1H, J )
12.5, 2.2 Hz, glu H6′b), 4.15 (m, 1H, glu H6b), 4.35 (dd, 1H, J )
12.5, 4.5 Hz, glu H6′a), 4.48 (dd, 1H, J ) 12.2, 1.6 Hz, glu H6a),
4.55 (d, 1H, J ) 8.0 Hz, glu H1′), 4.94 (dd, 1H, J ) 9.4, 8.0 Hz,
glu H2′), 5.08 (t, 1H, J ) 9.2 Hz, glu H2), 5.10 (t, 1H, J ) 9.4
Hz, glu H4′), 5.18 (t, 1H, J ) 9.4 Hz, glu H3′), 5.47 (t, 1H, J )
9.2 Hz, glu H3), 6.51 (d, 1H, J ) 7.3 Hz, H5 pyr), 7.14 (d, 1H,
J ) 9.2 Hz, glu H1), 7.41 (d, 1H, J ) 7.3 Hz, H6 pyr). 13C NMR
(CDCl3) δ: 14.3 (CH3S), 21.7 and 22.0 (7 COCH3), 62.8 and
63.0 (glu C6′ and C6), 69.0 (glu C2), 72.1 (glu C5′), 72.1 (glu C4′),
73.0 (glu C2′), 73.3 (glu C3), 74.0 (glu C3′), 77.2 (glu C4 and C5),
87.0 (glu C1), 101.7 (glu C1′), 109.6 (C5 pyr), 140.4 (C6 pyr),
170.2, 170.5, 171.4 and 171.7 (7 COCH3 and CdN), 183.0 (Cd
S). MS: m/z 777 ([M + H]+), 717 (100), 331. HRMS (DCI): m/z
calcd for C31H41N2O17S2 [M + H]+ 777.1847, found 777.1851.
1,1-Dim et h yl-4-m et h ylsu lfa n yl-1,5-d ia za p en t a d ien i-
u m Iod id e (5). A suspension of thiabutadiene 4 (1 g, 7.7
mmol) in methyl iodide (6 mL) and tetrahydrofuran (6 mL)
was stirred for 18 h at room temperature. The mixture was
evaporated under reduced pressure. After addition of diethyl
ether (40 mL), compound 5 was precipitated and collected by
filtration to leave a white solid, which was dried under vacuum
(2.02 g, 74.3 mmol, 96%). Mp: 182-184 °C. IR (KBr): 3257,
1
3107, 1632, 1533, 1282, 1056 cm-1. H NMR (D2O) δ: 2.55 (s,
3H, CH3S), 3.03 (s, 3H, N(CH3)2), 3.27 (s, 3H, N(CH3)2), 5.36
(d, 1H, J ) 12.2 Hz, CHCS), 7.95 (d, 1H, J ) 12.2 Hz, CHN).
13C NMR (D2O) δ: 13.1 (CH3S), 37.5 and 45.6 (N(CH3)2), 89.2
1-(2,3,6,2′,3′,4′,6′-Hep ta -O-a cetyl-â-D-la ctop yr a n osyl)-4-
m eth ylsu lfa n yl-1,2-d ih yd r op yr im id in -2-th ion e (7d ). Yel-
low crystals (yield 73%). Mp: 131-133 °C. IR (KBr): 1753,
(CHCS), 156.7 (CHN), 176.3 (CSCH3). Anal. Calcd for C6H13
-
1
1613, 1493, 1226 cm-1. H NMR (CD3COCD3) δ: 1.92 (s, 3H,
IN2S: C, 26.48; H, 4.81; N, 10.29. Found: C, 26.22; H, 5.03;
N, 10.97.
COCH3), 1.94 (s, 3H, COCH3), 2.07 (s, 3H, COCH3), 2.09 (s,
3H, COCH3), 2.10 (s, 3H, COCH3), 2.11 (s, 3H, COCH3), 2.16
(s, 3H, COCH3), 2.59 (s, 3H, CH3S), 4.17-4.29 (m, 6H, glu H4,
H5, H6b and gal H5, H6a, H6b), 4.64 (d, 1H, J ) 10.3 Hz, glu
P yr im id in e Nu cleosid e (7). Diazapentadienium iodide 5
(0.42 mmol) was added to a solution of glycoside isothiocyan-
ates 3a -f (0.85 mmol) in dichloromethane (20 mL). After 1 h
of stirring at room temperature, the reaction mixture was
cooled to 0 °C, and triethylamine (0.85 mmol) was added. The
mixture was stirred at room temperature for an additional 2
h, and then the solvent was removed in vacuo. The resulting
residue was partitioned between CH2Cl2 (20 mL) and water
(2 × 20 mL). The organic extract was dried (MgSO4), filtered,
and evaporated. The residue was purified by flash chroma-
tography on silica using hexane/AcOEt (9/1) and then hexane/
AcOEt (4/6) mixture as eluent to give compounds 7 and 8.
H
6a), 4.94 (m, 1H, gal H1), 5.08-5.15 (m, 2H, gal H2 and H3),
5.25 (t, 1H, J ) 8.9 Hz, glu H2), 5.39 (s, 1H, gal H4), 5.58 (t,
1H, J ) 8.9 Hz, glu H3), 6.81 (d, 1H, J ) 7.1 Hz, H5 pyr), 7.28
(d, 1H, J ) 8.9 Hz, glu H1), 8.06 (d, 1H, J ) 7.1 Hz, H6 pyr).
13C NMR (CD3COCD3) δ: 12.8 (CH3S), 20.6 (7 COCH3), 61.9
(gal C6), 62.9 (glu C6), 68.1 (gal C5), 69.9 (gal C4), 71.5 and
71.7 (gal C2 and C3), 72.5 (glu C2 and C3), 76.7 (glu C4 and C5),
86.4 (glu C1), 101.6 (gal C1), 108.6 (C5 pyr), 142.4 (C6 pyr),
169.6, 169.8, 170.2, 170.8 and 171.5 (7 COCH3 and CdN),
182.0 (CdS). MS: m/z 777 ([M + H]+), 71, 559, 331 (100).
HRMS (DCI): m/z calcd for C31H41N2O17S2 [M + H]+ 777.1847,
found 777.1836.
1-(2,3,4,6-Tet r a -O-a cet yl-â-D-glu cop yr a n osyl)-4-m et h -
ylsu lfan yl-1,2-dih ydr opyr im idin -2-th ion e (7a). Yellow crys-
tals (yield 84%). Mp: 94-96 °C. IR (KBr): 1753, 1612, 1492,
1
1223 cm-1. H NMR (CDCl3) δ: 2.00 (s, 3H, COCH3), 2.02 (s,
1-(2,3,5-Tr i-O-ben zoyl-â-D-r ibofu r a n osyl)-4-m eth ylsu l-
fa n yl-1,2-d ih yd r op yr im id in -2-th ion e (7e). Yellow crystals
(yield 72%). Mp: 89-91 °C. IR (KBr): 1727, 1601, 1450, 1269
3H, COCH3), 2.06 (s, 3H, COCH3), 2.08 (s, 3H, COCH3), 2.60
(s, 3H, CH3S), 4.01 (ddd, 1H, J ) 9.5, 5.1, 2.0 Hz, glu H5), 4.10
(dd, 1H, J ) 12.6, 2.0 Hz, glu H6b), 4.29 (dd, 1H, J ) 12.6, 5.1
Hz, glu H6a), 5.14 (t, 2H, J ) 9.5 Hz, glu H2 and H4), 5.49 (t,
1H, J ) 9.5 Hz, glu H3), 6.56 (d, 1H, J ) 7.2 Hz, H5 pyr), 7.23
(d, 1H, J ) 9.5 Hz, glu H1), 7.49 (d, 1H, J ) 7.2 Hz, H6 pyr).
13C NMR (CDCl3) δ: 13.1 (CH3S), 20.5 and 20.7 (4 COCH3),
61.6 (glu C6), 67.9 and 71.0 (glu C2 and C4), 72.4 (glu C3), 75.2
(glu C5), 85.7 (glu C1), 108.6 (C5 pyr), 139.4 (C6 pyr), 169.6,
170.0, 170.5 and 173.1 (4 COCH3 and CdN), 181.3 (CdS).
MS: m/z 489 ([M + H]+), 331 (100). HRMS (CI): m/z calcd for
1
cm-1. H NMR (CDCl3) δ: 2.61 (s, 3H, CH3S), 4.66 (dd, 1H, J
) 12.6, 3.2 Hz, rib H5b), 4.84 (ddd, 1H, J ) 7.0, 3.2, 2.4 Hz, rib
H4), 4.91 (dd, 1H, J ) 12.6, 2.4 Hz, rib H5a), 5.77 (dd, 1H, J )
7.0, 5.3 Hz, rib H3), 5.94 (dd, 1H, J ) 5.3, 3.0 Hz, rib H2), 6.32
(d, 1H, J ) 7.3 Hz, H5 pyr), 7.22 (d, 1H, J ) 3.0 Hz, rib H1),
7.30-7.69 (m, 9H, CHar meta and CHar para), 7.86 (d, 2H, J
) 8.5 Hz, CHar ortho), 7.96 (d, 1H, J ) 7.3 Hz, H6 pyr), 8.07
(m, 4H, CHar ortho). 13C NMR (CDCl3) δ: 13.1 (CH3S), 62.6
(rib C5), 69.4 (rib C3), 75.0 (rib C2), 80.1 (rib C4), 92.0 (rib C1),
108.3 (C5 pyr), 128.5, 128.8, 129.6 and 130.1 (3 Car, 6 CHar
meta, 3 CHar para), 133.7 (6 CHar ortho), 138.1 (C6 pyr), 164.8
and 172.8 (3 COC6H5 and CdN), 180.0 (CdS). MS m/z 603
([M + H]+), 359 (100), 297, 123. HRMS (DCI): m/z calcd for
C
19H25N2O9S2 [M + H]+ 489.1002, found 489.1005.
1-(2,3,4,6-Tetr a -O-a cetyl-â-D-ga la ctop yr a n osyl)-4-m eth -
ylsu lfan yl-1,2-dih ydr opyr im idin -2-th ion e (7b). Yellow crys-
tals (yield 82%). Mp: 93-95 °C. IR (KBr): 1749, 1613, 1493,
C
31H27N2O7S2 [M + H]+ 603.1260, found 603.1302.
1
1224 cm-1. H NMR (CDCl3) δ: 2.01 (s, 3H, COCH3), 2.03 (s,
3H, COCH3), 2.06 (s, 3H, COCH3), 2.20 (s, 3H, COCH3), 2.62
(s, 3H, CH3S), 4.11-4.22 (m, 2H, gal H6a and H6b), 4.13 (dd,
1H, J ) 7.1, 2.7 Hz, gal H4), 5.27-5.31 (m, 1H, gal H5), 5.29
(dd, 1H, J ) 8.3, 0.8 Hz, gal H2), 5.54 (dd, 1H, J ) 2.7, 0.8 Hz,
gal H3), 6.58 (d, 1H, J ) 7.3 Hz, H5 pyr), 7.21 (d, 1H, J ) 8.3
Hz, gal H1), 7.54 (d, 1H, J ) 7.3 Hz, H6 pyr). 13C NMR (CDCl3)
δ: 13.1 (CH3S), 20.5 and 20.7 (4 COCH3), 61.2 (gal C6), 67.0
(gal C3), 68.7 (gal C2), 70.6 (gal C5), 74.1 (gal C4), 86.2 (gal C1),
108.6 (C5 pyr), 139.8 (C6 pyr), 169.0 and 170.4 (4 COCH3 and
CdN), 180.0 (CdS). MS: m/z 489 ([M + H]+), 331 (100). HRMS
(CI): m/z calcd for C19H25N2O9S2 [M + H]+ 489.1002, found
489.0999.
1-(2,3,5-Tr i-O-ben zoyl-â-D-xylofu r a n osyl)-4-m eth ylsu l-
fa n yl-1,2-d ih yd r op yr im id in -2-th ion e (7f). Yellow crystals
(yield 83%). Mp: 89-91 °C. IR (KBr): 1728, 1600, 1450, 1260,
1
1090, 707 cm-1. H NMR (CDCl3) δ: 2.65 (s, 3H, CH3S), 4.73
(dd, 1H, J ) 12.3, 4.2 Hz, xyl H5a), 4.87 (dd, 1H, J ) 12.3, 4.2
Hz, xyl H5b), 5.03 (m, 1H, xyl H4), 5.77 (d, 1H, J ) 3.1 Hz, xyl
H3), 5.94 (s, 1H, xyl H2), 6.55 (d, 1H, J ) 7.3 Hz, H5 pyr), 6.79
(s, 1H, xyl H1), 7.34-7.64 (m, 9H, CHar meta and CHar para),
7.77 (dd, 2H, J ) 8.5, 1.4 Hz, CHar ortho), 7.92 (dd, 2H, J )
8.5, 1.4 Hz, CHar ortho), 8.15 (dd, 2H, J ) 8.6, 1.5 Hz, CHar
ortho), 8.21 (d, J ) 7.3 Hz, H6 pyr). 13C NMR (CDCl3) δ: 13.1
(CH3S), 61.4 (xyl C5), 74.6 (xyl C3), 80.2 and 81.9 (xyl C2 and
C4), 94.2 (xyl C1), 107.5 (C5 pyr), 128.1, 128.5, 128.6, 129.1,
129.7, 129.9, 130.2, 133.5, 133.8 and 134.1 (3 Car, 6 CHar
1-(2,3,6,2′,3′,4′,6′-Hepta-O-acetyl-â-D-cellobiopyr an osyl)-
4-m eth ylsu lfan yl-1,2-dih ydr opyr im idin -2-th ion e (7c). Yel-
8586 J . Org. Chem., Vol. 68, No. 22, 2003

Efficient Route to Pyrimidine Nucleoside Analogues
meta, 3 CHar para, and 6 CHar ortho), 139.3 (C6 pyr), 164.3,
164.4, 166.1 and 172.8 (3 COC6H5 and CdN), 179.4 (CdS).
MS: m/z 603 ([M + H]+), 359, 123 (100). HRMS (DCI): m/z
calcd for C31H27N2O7S2 [M + H]+ 603.1260, found 603.1267.
N,N-Dim eth yl-N′-(2,3,4,6-tetr a -O-a cetyl-â-D-glu cop yr a -
n osyl)th iou r ea (8a ). Yellow crystals (yield 72%). Mp: 72-
74 °C. IR (KBr): 1750, 1550, 1229, 1067 cm-1. 1H NMR (CDCl3)
δ: 2.03 (s, 3H, COCH3), 2.06 (s, 3H, COCH3), 2.07 (s, 3H,
COCH3), 2.08 (s, 3H, COCH3), 3.25 (br s, 6H, N(CH3)2), 3.88
(ddd, 1H, J ) 9.5, 4.6, 2.0 Hz, glu H5), 4.11 (dd, 1H, J ) 12.5,
2.0 Hz, glu H6b), 4.32 (dd, 1H, J ) 12.5, 4.6 Hz, glu H6a), 5.00
(t, 1H, J ) 9.5 Hz, glu H2), 5.08 (t, 1H, J ) 9.5 Hz, glu H4),
5.40 (t, 1H, J ) 9.5 Hz, glu H3), 5.77 (dd, 1H, J ) 8.2, 9.5 Hz,
glu H1), 6.41 (d, 1H, J ) 8.2 Hz, NH). 13C NMR (CDCl3) δ:
20.6, 20.8 and 20.9 (4 COCH3 and N(CH3)2), 61.7 (glu C6), 68.5
(glu C4), 71.2 (glu C2), 72.6 (glu C5), 73.2 (glu C3), 83.7 (glu
C1), 169.7, 170.7 and 172.2 (4 COCH3), 182.1 (CdS). MS: m/z
435 ([M + H]+), 403, 331 (100), 213. HRMS (CI): m/z calcd for
68.9 (gal C2), 70.8 and 71.0 (gal C3 and C5), 71.5 and 72.0 (glu
2, C3 and C5), 74.1 (glu C4), 83.6 (glu C1), 100.8 (gal C1), 169.0,
C
169.3, 170.1, 170.4 and 172.5 (7 COCH3), 182.1 (CdS). MS:
m/z 723 ([M + H]+), 331 (100). HRMS (DCI): m/z calcd for
C
29H43N2O17S [M + H]+ 723.2282, found 723.2296.
N,N-Dim eth yl-N′-(2,3,5-tr i-O-ben zoyl-D-r ibofu r a n osyl)-
th iou r ea (8e). Yellow oil (yield 75%). Mixture of anomer R
and â. Mp: 69-71 °C. IR (KBr): 1726, 1600, 1538, 1269, 709
cm-1 1H NMR (CDCl3) δ: 3.22 (br s, 12H, N(CH3)2), 4.57-
.
4.75 (m, 6H, rib H4, H5a and H5b), 5.82-5.92 (m, 4H, rib H2
and H3), 6.39 (d, 1H, J ) 7.3 Hz, NH of one anomer), 6.50-
6.57 (m, 2H, NH of one anomer and rib H1 of one anomer),
6.93 (dd, 1H, J ) 8.5, 4.8 Hz, rib H1 of one anomer), 7.34-
7.51 (m, 12H, CHar meta), 7.51-7.62 (m, 6H, CHar para), 7.89
(dd, 2H, J ) 8.3, 1.3 Hz, CHar ortho), 7.93 (dd, 2H, J ) 8.4,
1.3 Hz, CHar ortho), 7.97 (dd, 2H, J ) 8.5, 1.4 Hz, CHar ortho),
8.04 (dd, 2H, J ) 8.5, 1.4 Hz, CHar ortho), 8.10 (dd, 4H, J )
7.1 Hz, J ) 1.2 Hz, CHar ortho). 13C NMR (CDCl3) δ: 40.5
(N(CH3)2), 64.3 (rib C5), 70.8, 71.9, 73.4 and 74.1 (rib C2 and
C3), 78.8 and 79.4 (rib C4), 84.6 (rib C1 of one anomer), 87.6
(rib C1 of one anomer), 128.5, 128.6, 129.5, 129.7, 129.8 and
129.9 (6 Car, 12 CHar meta and 12 CHar ortho), 133.3, 133.4,
133.7 and 133.8 (6 CHar para), 164.5, 165.1, 165.6, 166.0 and
166.2 (6 COC6H5), 181.9 and 182.1 (CdS). MS: m/z 549 ([M +
H]+), 445 (100), 123. HRMS (DCI): m/z calcd for C29H29N2O7S
[M + H]+ 549.1694, found 549.1680.
C
17H27N2O9S [M + H]+ 435.1436, found 435.1440.
N,N-Dim eth yl-N′-(2,3,4,6-tetr a -O-a cetyl-â-D-ga la ctop y-
r a n osyl)th iou r ea (8b). Yellow crystals (yield 82%). Mp:
192-194 °C. IR (KBr): 1746, 1548, 1227, 1084 cm-1. 1H NMR
(CDCl3) δ: 2.01 (s, 3H, COCH3), 2.05 (s, 3H, COCH3), 2.09 (s,
3H, COCH3), 2.15 (s, 3H, COCH3), 3.26 (br s, 6H, N(CH3)2),
4.07-4.19 (m, 3H, gal H4, H6a and H6b), 5.19 (d, 1H, J ) 8.1
Hz, gal H2), 5.18-5.21 (m, 1H, gal H5), 5.47 (d, 1H, J ) 2.7
Hz, gal H3), 5.77 (t, 1H, J ) 8.1 Hz, gal H1), 6.44 (d, 1H, J )
8.1 Hz, NH). 13C NMR (CDCl3) δ: 19.5, 19.6, 19.8 and 20.0 (4
COCH3 and N(CH3)2), 60.1 (gal C6), 66.0 (gal C3), 67.8 (gal C2),
70.0 (gal C5), 71.1 (gal C4), 83.0 (gal C1), 168.7, 169.1, 169.5
and 171.3 (4 COCH3), 181.0 (CdS). MS: m/z 435 ([M + H]+,
100), 403, 331. HRMS (CI): m/z calcd for C17H27N2O9S [M +
H]+ 435.1436, found 435.1431
N,N-Dim eth yl-N′-(2,3,5-tr i-O-ben zoyl-D-xylofu r a n osyl)-
th iou r ea (8f). Yellow oil (yield 82%). Mixture of anomers R
and â. An om er R or â: Rf ) 0.43 (hexane/AcOEt 6/4). IR
1
(KBr): 1725, 1600, 1536, 1262, 708 cm-1. H NMR (CDCl3) δ:
3.20 (br s, 6H, N(CH3)2), 4.64 (d, 2H, J ) 5.3 Hz, xyl H5a and
H
5b), 4.86 (q, 1H, J ) 5.3 Hz, xyl H4), 5.82 (t, 1H, J ) 3.7 Hz,
xyl H2), 5.90 (dd, 1H, J ) 5.3, 3.7 Hz, xyl H3), 6.27 (d, 1H, J )
7.7 Hz, NH), 6.49 (dd, 1H, J ) 7.7, 3.7 Hz, xyl H1), 7.35-7.65
(m, 9H, CHar meta and para), 7.97-8.03 (m, 4H, Har ortho),
8.07 (dd, 2H, J ) 8.4, 1.3 Hz, Har ortho). 13C NMR (CDCl3) δ:
40.6 (N(CH3)2), 62.5 (xyl C5), 75.3 and 75.7 (xyl C3 and C4),
79.5 (xyl C2), 88.6 (xyl C1), 128.6, 128.7, 128.9, 129.7, 130.1,
133.3 and 133.8 (3 Car, 6 CHar meta, 6 CHar ortho, and 3
CHar para), 165.0, 165.5 and 166.2 (3 COC6H5), 181.6 (CdS).
An om er R or â: Rf ) 0.34 (hexane/AcOEt 6/4). IR (KBr): 1725,
N,N-Dim eth yl-N′-(2,3,6,2′,3′,4′,6′-h ep ta -O-a cetyl-â-D-cel-
lobiop yr a n osyl)th iou r ea (8c). Yellow crystals (yield 80%).
1
Mp: 112-114 °C. IR (KBr): 1748, 1548, 1230, 1040 cm-1. H
NMR (CDCl3) δ: 1.98 (s, 3H, COCH3), 2.00 (s, 3H, COCH3),
2.04 (s, 3H, COCH3), 2.05 (s, 3H, COCH3), 2.06 (s, 3H, COCH3),
2.09 (s, 3H, COCH3), 2.12 (s, 3H, COCH3), 3.21 (br s, 6H,
N(CH3)2), 3.65 (ddd, 1H, J ) 9.2, 4.6, 2.1 Hz, glu H5′), 3.70-
3.77 (m, 2H, glu H4 and glu H5), 4.03 (dd, 1H, J ) 12.4, 2.1
Hz, glu H6′b), 4.14 (dd, 1H, J ) 11.7, 4.5 Hz, glu H6b), 4.35 (dd,
1H, J ) 12.4, 4.6 Hz, glu H6′a), 4.47 (d, 1H, J ) 8.0 Hz, glu
H1′), 4.45-4.55 (m, 1H, glu H6a), 4.91 (t, 1H, J ) 9.3 Hz, glu
H2), 4.93 (dd, 1H, J ) 9.2, 8.0 Hz, glu H2′), 5.05 (t, 1H, J ) 9.2
Hz, glu H4′), 5.13 (t, 1H, J ) 9.2 Hz, glu H3′), 5.33 (t, 1H, J )
9.3 Hz, glu H3), 5.67 (dd, 1H, J ) 9.3, 8.0 Hz, glu H1), 6.37 (d,
1H, J ) 8.0 Hz, NH). 13C NMR (CDCl3) δ: 20.5, 20.7 and 20.9
(7 COCH3 and N(CH3)2), 61.7 (glu C6′), 62.1 (glu C6), 67.9 (glu
C4′), 71.5 (glu C2, C2′ and C5′), 72.0 (glu C3 and C3′), 72.9 (glu
C5), 74.1 (glu C4), 83.6 (glu C1), 100.6 (glu C1′), 169.0, 169.3,
170.2, 170.4, 170.5 and 172.5 (7 COCH3), 182.1 (CdS). MS:
m/z 723 ([M + H]+), 619, 331 (100). HRMS (DCI): m/z calcd
for C29H43N2O17S [M + H]+ 723.2282, found 723.2301.
1600, 1536, 1262, 708 cm-1 1H NMR (CDCl3) δ: 3.21 (br s,
.
6H, N(CH3)2), 4.56 (dd, 1H, J ) 11.6, 5.8 Hz, xyl H5a), 4.67
(dd, 1H, J ) 11.6, 5.9 Hz, xyl H5b), 4.87 (m, 1H, xyl H4), 5.80
(dd, 1H, J ) 4.2, 1.8 Hz, xyl H2), 5.89 (dd, 1H, J ) 4.2, 1.8 Hz,
xyl H3), 6.12 (d, 1H, J ) 9.0 Hz, NH), 7.02 (dd, 1H, J ) 9.0,
4.2 Hz, xyl H1), 7.40-7.70 (m, 9H, CHar meta and CHar para),
8.01 (dd, 2H, J ) 8.6 Hz, J ) 1.5 Hz, CHar ortho), 8.04-8.11
(m, 4H, CHar ortho). 13C NMR (CDCl3) δ: 40.6 (N(CH3)2), 62.4
(xyl C5), 75.3 and 75.6 (xyl C2 and C3), 76.2 (xyl C4), 85.5 (xyl
C1), 128.4, 128.5, 128.6, 128.9, 130.0, 133.2, 133.3, 133.8 and
134.1 (3 Car, 6 CHar meta, 6 CHar ortho, and 3 CHar para),
164.1, 165.0 and 166.1 (3 COC6H5), 181.5 (CdS). MS: m/z 549
([M + H]+), 445, 305, 123 (100). HRMS (DCI): m/z calcd for
N,N-Dim eth yl-N′-(2,3,6,2′,3′,4′,6′-h ep ta -O-a cetyl-â-D-la c-
top yr a n osyl)th iou r ea (8d ). Yellow crystals (yield 73%).
C
29H29N2O7S [M + H]+ 549.1696, found 549.1688.
1
Mp: 123-125 °C. IR (KBr): 1749, 1548, 1231, 1083 cm-1. H
Ack n ow led gm en t. We are grateful to the French
NMR (CDCl3) δ: 1.96 (s, 3H, COCH3), 2.06 (s, 6H, 2 COCH3),
2.07 (s, 6H, 2 COCH3), 2.12 (s, 3H, COCH3), 2.17 (s, 3H,
COCH3), 3.22 (br s, 6H, N(CH3)2), 3.76-3.86 (m, 2H, glu H4
and gal H5), 4.07-4.15 (m, 3H, glu H6b, gal H6a and H6b), 4.20
(dd, 1H, J ) 4.5, 2.2 Hz, glu H5), 4.43 (d, 1H, J ) 7.8 Hz, gal
H1), 4.41-4.46 (m, 1H, glu H6a), 4.92 (t, 1H, J ) 9.1 Hz, glu
H2), 4.94 (dd, 1H, J ) 10.4, 2.9 Hz, gal H3), 5.11 (dd, 1H, J )
10.4, 7.8 Hz, gal H2), 5.36 (d, 1H, J ) 2.9 Hz, gal H4), 5.39 (m,
1H, glu H3), 5.69 (dd, 1H, J ) 9.1, 7.9 Hz, glu H1), 6.38 (d, 1H,
J ) 7.9 Hz, NH). 13C NMR (CDCl3) δ: 20.6 and 20.9 (7 COCH3
and N(CH3)2), 61.0 and 62.1 (glu C6 and gal C6), 66.7 (gal C4),
Ministry of Education and the CNRS for financial
support.
Su p p or tin g In for m a tion Ava ila ble: General procedures,
1
copies of H and 13C NMR for compounds 4 and 5, and copies
of 1H, 13C NMR, and 2D NMR (COSY and HMQC) for
compounds 7a -f and 8a -f (except COSY of one anomer 8f).
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O034709A
J . Org. Chem, Vol. 68, No. 22, 2003 8587