Synthesis and antiviral evaluation of novel 6'(alpha)-methyl-branched Carbovir analogues.
A new stereoselective synthesis of 6'-branched Carbovir analogues was accomplished in this study. The introduction of a methyl group in the requisite 6'(alpha)-position was carried out using an ester enolate alkylation (LHMDS, CH3I). The desired cyclopentenol 7 was synthesized via a Felkin-Anh-controlled Grignard addition and ring-closing metathesis using second-generation Grubbs' catalyst. The natural bases (adenine, cytosine) were efficiently coupled using a Pd(0) catalyst. When the synthesized compounds were examined for their activity against several viruses such as the HIV-1, HSV-1, HSV-2, and HCMV, the adenine analogue 12 exhibited moderate antiviral activity against the HCMV.
Kim
Jin Woo
JW
College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
Hong
Joon Hee
JH
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003587:Cytomegalovirus / Q000187:drug effects; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D009705:Nucleosides; C057503:carbovir