Synthesis of analogues of lycoperdic acid to probe glutamate receptors in the central nervous system

ORGN 554

William R. F. Goundry, Victor Lee, and Jack E. Baldwin. Department of Chemistry, Oxford University, The Dyson Perrins Laboratory, South Parks Road, Oxford, OX1 3QY, United Kingdom
Both kaitocepalin 1 and dysiherbaine 2 contain the structural motif of lycoperdic acid 3 yet 1 is a powerful antagonist of glutamate receptors in the central nervous system (CNS) whilst 2 is an agonist. Antagonists of glutamate receptors have great potential in the treatment of a variety of CNS disorders including epilepsy and brain damage from strokes. Through the synthesis and biological testing of analogues of lycoperdic acid 3 a greater knowledge of these receptors can be acquired.

Our analogue 4 consists of a five membered heterocyclic ring spiro linked to glutamic acid. Key reactions involved in the efficient synthesis of 4 are a Claisen rearrangement, a chiral glycine anion alkylation, and an acid induced cyclization onto an epoxide. For greater diversity the diastereoisomers are prepared concurrently via a non selective epoxidation prior to cyclization. Our continuing work includes, varying the heteroatom and introducing side chains to the analogue.

 

Bioorganic, Molecular Recognition, Asymmetric Reactions and Syntheses
11:00 AM-1:00 PM, Wednesday, September 10, 2003 Javits Convention Center -- Hall 1B/1C, Poster

Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003