Synthesis of novel 2'-methyl carbovir analogues as potent antiviral agents.
In this study, the synthesis procedures of 2'-branched carbovir analogues were accomplished. The introduction of a methyl group in the requisite 2'-position was carried out by the addition of a carbonyl using isopropenyl magnesium bromide. The desired compound, cyclopentenol 10(beta), was synthesized via ring-closing metathesis using a second-generation Grubbs' catalyst. The nucleosidic bases (adenine, cytosine, thymine, uracil, 5-fluorouracil and 5-iodouracil) were efficiently coupled using a Pd (0) catalyst. When the synthesized compounds were examined for their activity against several viruses, including HIV-1, HSV-1, HSV-2 and HCMV, the 5-iodouracil analogue, 23, exhibited significant anti-HCMV activity.
Hong
Joon Hee
JH
BK-21 Project Team, College of Pharmacy, Chosun University, Kwangju 501-759, Korea. hongjh@chosun.ac.kr
D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003587:Cytomegalovirus / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006678:HIV / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C057503:carbovir