Biosynthetic study of chaetoglobosin A: origins of the oxygen and hydrogen atoms, and indirect evidence for biological Diels–Alder reaction

The biosynthetic origins of the oxygen and hydrogen atoms in the mycotoxin Chaetoglobosin A 1 have been investigated by the incorporation of sodium [1-13C,18O2]-, [1-13C,2H3]-acetate and 18O2 gas into the mycotoxin by using the chaetoglobosin-producing strain Chaetomium subaffine. Considering the results of the P-450 inhibitor experiment, the results obtained from the above experiments support the biogenetic pathway proposed. Attempts at direct conversion of 14C- or 13C-labelled prochaetoglobosin l 2 using whole cells were unsuccessful. Formation of the diastereoisomer 10 of 2 in the retro-Diels–Alder reaction of compound 2 has provided indirect evidence that the plausible precursor hexaene 6 is able to cyclize via[4 + 2]cycloaddition in the biosynthesis of Chaetoglobosin A 1.