Tuesday, 24 May 2005

This presentation is part of: Organic Posters

Total Synthesis of Cyclopeptide Alkaloid Hymenocardine

Galina V. Kapustin, Rao N. Nallagancho, Weiying Yang, and Madeleine M. Joulliť. University of Pennsylvania, Philadelphia, PA

Hymenocardine, a 14-membered cyclic peptide alkaloid containing a p-ansa structure with 10-membered peptide-type bridge, was isolated from roots of Hymenocardia acida Tul. in 1968 and has not been synthesized. The leaves and root extracts of Hymenocardia acida showed numerous medical indications including malaria, anti-trypanosomal, antitumor activity and some of these may be related to hymenocardine. This biological activity led us to synthesize hymenocardine for testing. We now wish to report the synthesis of this compound. Hymenocardine contains two nonproteinogenic amino acids, a ‚-phenoxy amino acid with a tertiary alkyl-aryl ether linkage in the cyclic core and dimethyl amino allo-L-isoleucine on the N-terminus of the side chain. The key steps of the synthesis are the construction of the tertiary alkyl-aryl ether linkage and the macrocyclization. The synthesis was started from D-Ser-OMe which after protection was converted to a tertiary alcohol with methyl Grignard reagent. A SNAr reaction was used for installation of the alkyl-aryl ether bond. Different strategies have been tried for macrolactonization step. The details of the synthesis will be discussed.

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