7-iodo-5-aza-7-deazaguanine: Syntheses of anomeric D- and L-configured 2-deoxyribonucleosides

Abstract

Iodination of N-2-isobutyryl-5-aza-7-deazaguanine (7) with N-iodosuccinimide (NIS) gave 7-iodo-N-2-isobutyryl-5-aza-7-deazaguanine (8) in a regioselective reaction (Scheme 1). Nucleobase-anion glycosylation of 8 with 2-deoxy-3,5-di-O-toluoyl-alpha-D- or alpha-L-erythro-pentofuranosyl chloride furnished anomeric mixtures of D-and L-nucleosides. The anomeric D-nucleosides were separated by crystallization to give the a-D-anomer and beta-D-anomer with excellent optical purity. Deprotection gave the 7-iodo-5-aza-7-deazaguanine 2'-deoxyribonucleosides 3 (beta-D; greater than or equal to 99% de) and 4 (alpha-D; greater than or equal to 99% de). The reaction sequence performed with the D-series was also applied to L-nucleosides to furnish compounds 5 (beta-L; greater than or equal to 99% de) and 6 (alpha-L; greater than or equal to 95% de).