6533b85afe1ef96bd12b9eb9

RESEARCH PRODUCT

Studies on the biosynthesis of paraherquamide. Construction of the amino acid framework

subject

description

Abstract It has been previously established in this laboratory that the β-methyl-β-hydroxyproline moiety of the potent anthelmintic agent paraherquamide A, is biosynthetically derived from l -isoleucine. The downstream events from l -Ile to paraherquamide A have now been investigated. The synthesis of [1- 13 C]-labeled l -β-methylproline is described by means of a Hoffman–Loeffler–Freytag reaction sequence from [1- 13 C]- l -Ile. This amino acid is shown to be a direct biosynthetic precursor to paraherquamide A by feeding and incorporation experiments in growing cultures of Penicillium fellutanum . Three tryptophan-containing dipeptides of l -β-methylproline have been constructed: [ 13 C 2 ]-2-(1,1-dimethyl-2-propenyl)- l -tryptophanyl-3( S )-methyl- l -proline; [ 13 C 2 ]-3( S )-methyl- l -prolyl-2-(1,1-dimethyl-2-propenyl)- l -tryptophan and [ 13 C 2 ]- cyclo -2-(1,1-dimethyl-2-propenyl)- l -tryptophan-3( S )-methyl- l -proline. [α- 15 N, 1- 13 C]-2-(1,1-Dimethyl-2-propenyl)- l -tryptophan was also prepared but none of these substances were found to serve as biosynthetic precursors to paraherquamide A.