3'-Carbon-substituted pyrimidine nucleosides having a 2',3'-dideoxy and 2',3'-didehydro-2',3'-dideoxy structure:
Hiroki Kumamoto1, Sayoko Onuma, Hiromichi Tanaka
1School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan. hirotnk@pharm.showa-u.ac.jp
Abstract:
The bis(tributylstannyl) derivative of 2',3'-didehydro-2',3'-dideoxyuridine (d4U) underwent an anionic 5'-O-->3'-C stannyl migration to yield the 3'-tributylstannyl-d4U. This compound, with its vinylstannane structure, allowed ready access to the preparation of 3'-carbon-substituted analogues through the Stille reaction. A conventional transformation of the uracil moiety of these d4U analogues led to the corresponding 2',3'-didehydro-2',3'-dideoxycytidine (d4C) counterparts. Some 2',3'-dideoxycytidine (ddC) analogues were also synthesized. Antiviral evaluation revealed that none of these analogues showed activity against HIV, hepatitis B virus, herpes simplex virus-1 (HSV-1) and HSV-2.
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