Biosynthesis of α-cyclopiazonic acid. Steric course of proton removal during the cyclisation of β-cyclopiazonic acid in Penicillium griseofulvum

Abstract

Feeding experiments with (3R)- and (3S)-[3-³H] tryptophan have shown that, in Penicillium griseofulvum Dierckx, incorporation of tryptophan into α-cycopiazonic acid (1) proceeds with loss of the 3-pro-S hydrogen atom. [3-²H₂]Tryptophan was converted by P. griseofulvum into α-cyclopiazonic acid which was shown by ²H n.m.r. spectroscopy to contain deuterium only at the expected C-4 position. (2RS)-[2-³H,3-¹⁴C]Tryptophan was incorporated into α-cyclopiazonic acid (1) with loss of ca. 50% of the tritium. These findings are consistent with cyclisation of β-cyclopiazonic acid (4) to α-cyclopiazonic acid (1)via a 1,4-didehydro-derivative, with C–C bond formation at C-4 occurring from the side of the molecule opposite to that from which proton removal takes place.