Biosynthetic studies on fluoroacetate and longianone

Abstract

This thesis explores the biosynthesis of two secondary metabolites, fluoroacetate and longianone, and involves the synthesis and feeding of deuterated putative intermediates. The bacterium Streptomyces cattleya produces fluoroacetate and 4- fluorothreonine; the mechanism by which C-F bond formation occurs is unknown. The stereochemistry of the fluorination event was investigated by feeding [2,2,3,3-(^-2)H(_4)]-succinate and (2R)-[l-(^2)H(_2)]- and (2S)-[l-(^2)H(_2)]-glycerols. The chirality of the resultant [2-(^2)H]-fluoroacetate was determined by chiral liquid crystal (^2)H-NMR and the fluorination was demonstrated to proceed with retention of stereochemistry. Longianone is produced by the slow growing fungus Xylaria longiana. This simple bicyclic metabolite is an isomer of the notorious fungal toxin patulin. Putative deuterated intermediates were administered to the fungus and the longianone produced analysed by (^2)H-NMR. It was demonstrated that longianone is biosynthesised from 6-methylsalicylic acid in a pathway closely related to that found in patulin biosynthesis.