Progress towards the synthesis of (-)-sordaricin

ORGN 186

Richard F. Heck, taberdf@udel.edu, Professor Emeritus of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 and Kevin J. Frankowski, 69175@udel.edu, Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716.
Sordaricin 7 is the naturally-occurring aglycone starting material for a series of semisynthetic antifungal agents that were under investigation for their unusual mode of action. This promising group of antifungal compounds was not pursued further because of the expense of sourcing (-)-sordaricin.

Our approach to the imposing cage-like scaffold of sordaricin is dependant on a regioselective C-H insertion of a free carbene intermediate. To investigate the feasibility of the proposed selective C-H insertion we are constructing the model ketone 5. The free carbene intermediate has two equally accessible methylene insertion sites. The desired regioisomer 6 would be formed by insertion at the methylene not deactivated remotely by an ester in the beta position. Key chemical transformations for the construction of ketone 5 include the palladium-catalyzed cyclization of silyl enol ether 1 to the sterically-encumbered bicyclic ketones 2 and 3 and subsequent homologation to the nitrile 4.

 

New Reactions and Methodology, Materials, Total Synthesis, Process R&D
8:00 PM-10:00 PM, Sunday, 28 August 2005 Washington DC Convention Center -- Hall A, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 29 August 2005 Washington DC Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005