Synthesis of Purine Nucleoside and Nucleotide Analogs as Antiparasitic Agents

摘要

The purpose of the research was to conduct studies on the synthesis of purine nucleoside and nucleotide analogs as antiparasitic agents. The primary target compounds were 5'-deoxytubercidin 5'-amino-5'-deoxytubercidin (nucleoside analogs) and 5'-fluoro-5'-deoxytubercidin (a nucleotide analog.) One target, 5'-deoxytubercidin, was successfully prepared in an efficient two-step procedure and submitted for screening. Several attempts to prepare the 5'-amino- and 5'-fluoro-derivatives of tubercidin either by direct routes or via blocked tubercidin were unsuccessful. Due to problems encountered in these attempted syntheses, work on 5'-derivatives of two other purine nucleoside antibiotics - puromycin aminonucleoside and 6-methylmercaptopurine riboside - was not initiated. However, work on 5'-derivatives of nebularine was performed and some success was achieved in this series. Nebularine was synthesized by a literature method and submitted for screening. A two-step synthesis of 5'-deoxynebularine from nebularine via 5'-deoxy-5'-iodonebularine was accomplished even though an analytical sample is not yet in hand.