On the Biosynthesis of Cyclopenin and Cyclopenol, Benzodiazepine Alkaloids from Penicillium cyclopium Westling

Abstract

By feeding of isotope labelled compounds to cultures of Penicillium cyclopium Westling and degradation of the cyclopenin (3‐benzyl‐3,10‐epoxy‐4‐methyl‐2,3,4,5‐tetrahydro‐1 H‐1,4‐benzodiazepine‐2,5‐dione) and cyclopenol [3‐(m‐hydroxy‐benzyl)‐3,10‐epoxy‐4‐methyl‐2,3,4,5‐tetrahydro‐1 H‐1,4‐benzodiazepine‐2,5‐dione] formed the biosynthesis of these alkaloids was investigated: The carbon skeletons of both alkaloids originate from all the C‐atoms of anthranilic acid and l‐phenylalanine and from the methyl group of methionine. N(1) and N(4) of the diazepine ring derive from all the nitrogen atoms of anthranilic acid and l‐phenylalanine respectively. For cyclopenol, of several phenylpropane compounds tested, only l‐phenylalanine is a direct precursor. Thus, the introduction of the m‐hydroxy group by a mixed functional oxygenase as one of the later steps of its biosynthesis appears very likely. Copyright © 1969, Wiley Blackwell. All rights reserved