3'-Carbon-substituted pyrimidine nucleosides having a 2',3'-dideoxy and 2',3'-didehydro-2',3'-dideoxy structure: synthesis and antiviral evaluation.
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.
Kumamoto
Hiroki
H
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan. hirotnk@pharm.showa-u.ac.jp
Onuma
Sayoko
S
Tanaka
Hiromichi
H
Dutschman
Ginger E
GE
Cheng
Yung-Chi
YC
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015224:Dideoxynucleosides / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D018139:Simplexvirus / Q000187:drug effects; D014709:Vero Cells; D016047:Zalcitabine / Q000138:chemical synthesis*
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D015224:Dideoxynucleosides; D011741:Pyrimidine Nucleosides; C058925:2',3'-didehydro-2',3'-dideoxyuridine; D016047:Zalcitabine