[Molecules: 6] [Related articles/posters: 005 074 036 117 056 ]

Synthesis of some bridged heterocycles with a saccharide moiety in the molecule

M. Koos, B. Steiner and J. Gajdos

Institute of Chemistry, Slovak Academy of Sciences, SK-84238 Bratislava, Slovak Republic

It is well known that combination of nitrogen-containing heterocycles with saccharides affords a very important group of organic compounds, especially from the point of view of their biological activity (e.g. nucleosides, nucleotides). Besides a variety of physiological functions, the sugar component can also be used to improve the solubility of these compounds in water.

We now report the synthesis of some compounds including combination of pyrazole or pyrimidine ring with imidazole ring and a saccharide component in the molecule.

Starting from the known methyl 2,3-O-isopropylidene-a-D-lyxo-pentodialdo-1,4-furanoside [1], the corresponding a-aminonitrile 1 was prepared as a mixture of diastereomers (considering that the C-5 asymmetric centre is destroyed in the next reaction step, separation of diastereomers was unnecessary) by the Strecker reaction [2]. Compound 1 reacted with phenyl isothiocyanate to give thiazole 2 which subsequently rearranged to 2-mercaptoimidazole 3upon treatment with base. Following S-alkylation of 3 with 3-chloro-2,4-pentanedione [3] afforded the corresponding b-diketone 4. Cyclization of this using hydrazine [4] or guanidine [5] resulted in the formation of pyrazole 5 or pyrimidine 6, respectively, bridged with sulfur to the imidazole ring. All these compounds possess a saccharide moiety in the 4 position of the imidazole ring.

The same results were also obtained starting from 3-O-benzyl-1,2-O-isopropylidene-a-D- xylo-pentodialdo-1,4-furanose [6] and methyl 2,3-O-isopropylidene-a-D-ribo-pentodialdo-1,4-furanoside [7] applying the above described reaction sequence. The ¹H-, ¹³C NMR, and mass spectral data of the prepared compounds were also studied.

References

1 Hanaya, T.; Ohmori, K.; Yamamoto, H.; Armour, M. -A.; Hogg, A. M. Bull. Chem. Soc. Jpn. 1990, 63, 1174-1179.

2 Steiner, B.; Koos, M. submitted for publication.

3 Koos, M. Chem Papers 1994, 48, 108-110.

4 Koos, M.; Steiner, B.; Repas, M. Chem. Papers 1991, 45, 279-286.

5 Brown, D. J.; England, B. T. J. Chem. Soc. (C) 1967, 1922-1927.

6 Kovar, J.; Baer, H. H. Carbohydr. Res. 1975, 39, 19-35.

7 Jones, G. H.; Moffatt, J. G. Methods Carbohydr. Chem. 1972, 6, 315-322.

Acknowledgments

Financial support of this research by the Scientific Grant Agency (VEGA, Slovak Academy of Sciences and Ministry of Education, Bratislava, Project 1231) is gratefully appreciated. We would like to thank Dr Henry Rzepa, Imperial College London, for his great work in organizing ECHET96 and his help during setup of our contribution.