Studies on the Biosynthesis of the Fungal Metabolite Oudenone. 2. Synthesis and Enzymatic Cyclization of an alpha-Diketone, Open-Chain Precursor into Oudenone in Cultures of Oudemansiella radicata

Youla S. Tsantrizos; Xianshu Yang; Andrew McClory

doi:10.1021/jo9901135

Studies on the Biosynthesis of the Fungal Metabolite Oudenone. 2. Synthesis and Enzymatic Cyclization of an alpha-Diketone, Open-Chain Precursor into Oudenone in Cultures of Oudemansiella radicata

J Org Chem. 1999 Sep 3;64(18):6609-6614. doi: 10.1021/jo9901135.

Authors

Youla S. Tsantrizos¹, Xianshu Yang, Andrew McClory

Affiliation

¹ Department of Chemistry & Biochemistry, Concordia University, Montreal, Quebec H3G 1M8, Canada, Department of Chemistry, Boehringer Ingelheim (Canada) Ltd., Bio-Méga Research Division, Laval, Quebec H7S 2G5, Canada, and Department of Chemistry, McGill University, Montreal, Quebec H3A 2K6, Canada.

PMID: 11674663
DOI: 10.1021/jo9901135

Abstract

The alpha-diketone 4 was shown to be the open-chain biosynthetic precursor of the fungal metabolite oudenone (1a and 1b). Intact incorporation of 4 into 1 was achieved upon incubation of a (2)H-labeled, N-acetylcysteamine thioester derivative of 4 with growing cultures of Oudemansiella radicata. A biosynthetic scheme for the formation of the hexaketide 4 and its enzymatic cyclization into oudenone (1), consistent with the experimental data, is described. The proposed mechanism for the cyclization of 4 to 1 is analogous to the "polyepoxide cascade" model, which has been previously implicated in the biosynthesis of polyether antibiotics.