Lipase mediated enantioselective synthesis of 2'-methylenecyclobutyl carbocyclic nucleosides

CARB 48

Lavanya Bondada, blavanya@rx.uga.edu, Department of Pharmaceutical and Biomedical Sciences, The University of Georgia, College of Pharmacy, Athens, GA 30602 and C. K. Chu, dchu@rx.uga.edu, Pharmaceutical Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30605.
The therapeutic importance of nucleoside related compounds gave impetus for the synthesis of new analogs as well as developing efficient synthetic strategies. The unique structure and biological activity of oxetanocin analogues have intensified the research in this class of nucleosides. Accordingly, D-and L-2'-methylenecyclobutyl nucleoside analogues were synthesized in enantiomerically pure forms. The synthesis involves lipase mediated enantioselective acetylation of racemic alcohol as a key step. The racemic alcohol, 2,3-O-cyclohexilidene-3-hydroxymethyl-1,2-cyclobutylmethanol was conveniently synthesized in 7-steps from diethoxyketene and diethylfumarate. Mitsunobu conditions were used for the introduction of heterocyclic bases. Our synthetic route also provides valuable chiral synthons for the synthesis of other cyclobutyl nucleosides. The biological evaluation of the synthesized nucleosides is in progress (Supported by NIH AI056540).
 

General Posters
6:00 PM-8:00 PM, Tuesday, 28 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster

Division of Carbohydrate Chemistry

The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006