Synthesis of novel 4 'alpha-phenyl and 5 'alpha-methyl branched carbocyclic nucleosides

Abstract

This paper describes the racemic and stereoselective synthetic route for a novel 4'alpha-phenyl and 6'alpha-methyl doubly branched carbocyclic nucleosides from an acyclic 2-hydroxy acetophenone. The installation of phenyl roup at the 4'-position of carbocyclic nucleoside was successfully accomplished via a sequential [3,3]sigmatropic rearrangement. The stereoselective introduction of a methyl group in the 6'alpha-position was accomplished by Felkin-Anh controlled alkylation. Bis-vinyl 11 compound was successfully cyclized using a Grubbs' catalyst II to desired carbocycles. The natural bases (adenine and cytosine) were efficiently coupled using a Pd(0) catalyst. Although all the synthesized compounds were examined for their activity against several viruses such as HIV-1, HSV-1, HSV-2 and HCMV, only cytosine analogues 17 exhibited weak antiviral activity against HCMV.