Asymmetric Synthesis and Biological Activity of l-Bicyclocarba-d4T

Abstract

Novel l-bicyclocarba-d4T (1), an enantiomer of d-N-MCd4T has been enantiopurely synthesized as a potent anti-HIV agent starting from (R)-epichlorohydrin using tandem alkylation, chemoselective reduction of ester in the presence of lactone functional group, Grignard reaction, RCM reaction, and Mitsunobu reaction as key steps. l-N-MCd4T (1) was found to be very potent anti-HIV-1 (EC₅₀ = 6.76 μg/mL) agent with no cytotoxicity.

Keywords:

• Anti-HIV agent
• novel l-bicyclocarba-d4T
• tandem alkylation
• (R)-epichlorohydrin

This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2005-202-E00211).