The biosynthesis of patulin

The biosynthesis of the antibiotic patulin (II) from 6-methylsalicyclic acid (6-MSA) (I) in replacement cultures of Penicillium patulum has been examined with ²H and ${}^{14}\text{C}{}^3\text{H}\text{-labeled}$ intermediates. Efficient utilization of m-cresol (IX), m-hydroxybenzyl alcohol (V), m-hydroxybenzaldehyde (XII), gentisaldehyde (VIII), and gentisyl alcohol (VI) could be demonstrated. Toluquinol (X), although inactive as a precursor of patulin, is converted by refloated cultures of P. patulum to desoxyepoxydon (XIII). Para-hydroxylation of m-cresol proceeds with loss of deuterium at the p-position. Side chain labeling of the aromatic precursors is lost in the conversion. A major portion of this work has been reported in preliminary form (1, 2).