Synthesis and antitubercular activity of nucleoside analogs based on l-ascorbic acid and bases

Abstract

5,6-O- isopropylidene-2,3- di-O- methyl ascorbic acid (2), obtained by reaction of acetone with ascorbic acid (1) followed by methylation with methyl iodide, on DBU catalysed elimination of acetone moiety led to the formation of respective 2,3-di-O-methyl didehydro-L-ascorbic acid (4) in good yield. The latter on methanesulphonylation with methanesulphonyl chloride and subsequent reaction of the crude methanesulphonyloxy derivative with imidazole, benzimidazole and adenine resulted in respective tetronolactonyl nucleoside analogs 5, 6 and 7. Compound 5 on reaction with benzyl amine led to N- benzylated teramyl nucleoside analog, while compounds 6 and 7 did not react under similar condition. All the synthesized compounds were evaluated for their antitubercular activity against M. tuberculosis H37Ra and H37Rv exhibiting MIC >12.5 µg/mL.