Nucleosides and nucleotides. 120. Stereoselective radical deoxygenation of tert-alcohols in the sugar moiety of nucleosides: synthesis of 2′,3′-dideoxy-2′- C-methyl- -2′- C-ethynyl-β- d- threo-pentofuranosyl pyrimidines and adenine as potential antiviral and antitumor agents

Abstract

Radical deoxygenation of 2′- O-methoxalyl ester of the corresponding 3′-deoxy-2′- C-methyl-β- d- threo-pentofuranosyl-pyrimidines and -adenine, which were readily obtained from the reaction of 1-(3-deoxy-β- d- erythro-pentofuran-2-ulosyl)pyrimidines and adenine derivatives with MeMgBr, gave stereospecifically 2′,3′-dideoxy-2′- C-methyl-β- d- threo-pentofuranosyl-uracil ( 9a), -thymine ( 9b), -cytosine ( 9c), and -adenine ( 18), respectively, after deprotection. Similarly, synthesis of 2′,3′-dideoxy-2′- C-ethynyl-β- d- threo-pentofuranosyl-thymine ( 25) and -adenine ( 31) was achieved by the reaction of the corresponding ketones with LiCCTMS, followed by radical deoxygenation of the tert-methoxaly ester. Cytotoxicity and anti-HIV activities of these nucleosides in vitro were described.