Tropolone Biosynthesis: the Enzymatic Decarboxylation of Stipitatonic and Puberulonic Acids

Abstract

ISOTOPE tracer studies have established an important role for acetate and formate in the biosynthesis of stipitatic acid (6-hydroxytropolone-4-carboxylic acid) by Penicillium stipitatum and it is probable¹ that the C₇ tropolone ring is not formed by ring expansion from known C₆ structures as proposed by Seshadri². Seshadri also suggested 6-hydroxytropolone-3,4-dicar-boxylic acid as the immediate precursor of stipitatic acid. This possibility seemed likely since other Penicillium species yielded the compounds puberulic and puberulonic acids³ which are now known to be 6,7-dihydroxytropolone-4-carboxylic acid and the anhydride of 6,7-dihydroxytropolone-3,4-dicarboxylic acid, respectively⁴. Recently Segal⁵ isolated from P. stipitatum cultures an anhydride, stipitatonic acid, originally believed to be the 6-hydroxytropolone-3,4-dicarboxylic acid proposed by Seshadri, but now established as the 4,5 isomer⁶. Although puberulonic acid is usually written as indicated above, it seems reasonable to suppose that any adjacent pair of the four oxygen functions may form the tropolone function and it may equally be regarded as 3,4-dihydroxytro-polone-5,6-dicarboxylic acid, or analogous to stipitatonic acid, as 3,7-dihydroxytropolone-4,5-dicarboxylic acid.