6533b829fe1ef96bd128a229

RESEARCH PRODUCT

ChemInform Abstract: Studies on the Biosynthesis of Paraherquamide. Construction of the Amino Acid Framework.

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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.