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Synthesis and Antiviral Evaluation of Novel 6′(α)‐Methyl‐Branched Carbovir Analogues
Author(s) -
Kim Jin Woo,
Hong Joon Hee
Publication year - 2005
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200500118
Subject(s) - chemistry , ring closing metathesis , stereochemistry , stereoselectivity , alkylation , chemical synthesis , grignard reaction , metathesis , catalysis , combinatorial chemistry , in vitro , organic chemistry , biochemistry , reagent , polymerization , polymer
A new stereoselective synthesis of 6′‐branched Carbovir analogues was accomplished in this study. The introduction of a methyl group in the requisite 6′(α)‐position was carried out using an ester enolate alkylation (LHMDS, CH 3 I). 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.