A synthesis of 2‐β‐D‐ribofuranosyl‐4‐selenazolecarboxamide (selenazofurin) and certain N‐substituted amide derivatives suitable for large scale syntheses

Abstract

A new process suitable for large scale synthesis of the antitumor‐antiviral agent, 2‐β‐D‐ribofuranosyl‐4‐selenazolecarboxamide (selenazofurin, 1), has been developed. Thus, 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose (3) was converted with cyanotrimethylsilane and stannic chloride to the crystalline 2,5‐anhydro‐3,4,6‐tri‐O‐benzoyl‐β‐D‐allononitrile (4) without chromatography. Cyanosugar 4 in ethanol was treated with hydrogen selenide gas to afford stereospecifically the unstable 2,5‐anhydro‐3,4,6‐tri‐O‐benzoyl‐β‐D‐allonoselenoamide (5) which was converted in situ by ethyl bromopyruvate to the stable ethyl 2‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)‐4‐selenazolecarboxylate (6). Selenazole ethyl ester 6 was deprotected with sodium methoxide affording methyl 2‐β‐D‐ribofuranosyl‐4‐selenazolecarboxylate (7) which was aminated with ammonia to provide selenazofurin (1) or with other amines to provide N‐substituted selenazofurin amides.

Biologically significant selenium-containing heterocycles

“…They developed the synthetic route similar to the preparation method of tiazofurin [73]. Treatment of the precursor, 2,3,5-tri-O-benzoyl--D-ribofuranosyl-1-carbonitrile [74,75] with hydrogen selenide, with 4-dimethylaminopyridine (DMAP) as a catalyst, provided 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonoselenoamide as a foamy material. The corresponding selenoamide was treated with ethyl bromopyruvate to give ethyl 2-(2,3,5-tri-O-benzoyl-D-ribofuranosyl)selenazole-4-carboxylates as a mixture of ,-anomers, which were readily separated by silica gel column chromatography.…”

“…Selenazofurin is a potent anti-viral agent in vitro, inhibiting the replication of such diverse viruses as paramyxoviruses, reoviruses, poxviruses, herpesviruses, togaviruses, bunyaviruses, arenaviruses, picornaviruses, adenoviruses, and rhabdoviruses [71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90]. In addition, selenazofurin demonstrates its significant anti-influenza A and B activities (IC 50 = 25 and 19 M, respectively) in vitro [91,92].…”

“…N-Substituted amide derivatives of selenazofurin were synthesized through aminolysis with several amines instead of ammonia (Scheme 6) [75]. IC 50 values of the amide derivatives 15a-15d against in vitro L1210 cells were greater than 100 M as compared with that of selenazofurin.…”