Asymmetric synthesis and biological activity of L-bicyclocarba-d4T.
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 (EC(50) = 6.76 microg/mL) agent with no cytotoxicity.
Moon
Hyung Ryong
HR
College of Pharmacy and Research Institute for Drug Development, Pusan National University, San 30 Jangjeon-dong, Geumjeong-gu, Busan 609-735, Korea. mhr108@pusan.ac.kr
Park
Ah-Young
AY
Kim
Kyung Ran
KR
Chun
Moon Woo
MW
Jeong
Lak Shin
LS
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C476440:1-(5-(hydroxymethyl)bicyclo(3.1.0)hex-3-en-2-yl)-5-methyl-1,3-dihydropyrimidine-2,4-dione; D019380:Anti-HIV Agents; D001643:Bridged Bicyclo Compounds; D013936:Thymidine