Peiming Zhang

An efficient route to C-4 linked imidazole nucleosides: synthesis of 2-carbamoyl-4-(2′-deoxy-β-d-ribofuranosyl)imidazole

The first synthesis of an imidazole C-nucleoside linked through C-4, 2-carbamoyl-4-(2′-deoxy-β-d-ribofuranosyl)imidazole was achieved by way of a nine-step sequence starting from 2-deoxy-3,5-di-O-p-toluoyl-d-erythro-pentofuranosyl chloride.

DESIGN AND SYNTHESIS OF HETEROCYCLIC CARBOXAMIDES AS NATURAL NUCLEIC ACID BASE MIMICS

Abstract A series of heterocyclic carboxamides have been designed as mimics for the natural nucleic acid bases. The nucleosides 1-(2′-deoxy-β-d-ribofuranosyl)imidazole-4-carboxamide (1), 1-(2′ -deoxy-β-d-ribofuranosyl)pyrazole-3-carboxamide (2), and 1-(2′ -deoxy-β-d-ribofuranosyl)pyrrole-3-carboxamide (3) were synthesized and their structures confirmed by spectroscopic and analytical means. This paper is dedicated to Dr. Yoshihisa Mizuno.

Synthesis of 2′-deoxy-β-D-ribofuranosyl imidazole and thiazole C-nucleosides

A synthetic route to 2-carbamoyl-4-(2′-deoxy-β-D-ribofuranosyl)imidazole 3, starting from 2-deoxy-3,5-di-O-toluoyl-β-D-ribofuranosyl cyanide 4, was developed. The key steps are reduction of the cyano group of compound 4 to a formyl and subsequent condensation with tosylmethyl isocyanide to yield the formamido derivative 7, which was dehydrated to an isocyanide and ring closed with either ammonia or a primary amine to yield protected C-4 linked imidazolyl deoxyribosyl derivatives 9a–c. Ring closure with H2S followed by removal of the toluoyl protecting groups with ammonia gave 5-(2′-deoxy-β-D-ribofuranosyl)thiazole 11. A cyano group can be introduced at C-2 of the imidazole nucleosides by way of the reagent N-cyano-4-(dimethylamino)pyridinium bromide. Subsequent hydrolysis of the cyano functional group with alkaline hydrogen peroxide yields a carboxamide substituent. All of the transformations were able to be carried out without affecting the β-configuration at the anomeric carbon. A p-nitrophenylethyl protecting group was introduced at N-3 of the imidazole during ring closure in order to obtain a protected derivative that could be selectively modified at the deoxyribosyl (erythro-pentofuranosyl) hydroxy groups.