On the Biosynthesis of Cyclopenin and Cyclopenol, Benzodiazepine Alkaloids from <i>Penicillium cyclopium</i> 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.