Yuko Yoshizawa

Biosynthesis of solanapyrone A, a phytotoxin of Alternaria solani

The building blocks and the origin of hydrogen and oxygen atoms in solanapyrone A (1) were determined by incorporation experiments employing sodium [1-13C]-, [1,2-13C2]-, [1-13C, 18O2]-, [1-13C, 2H3]-, [2-13C, 2H3]acetates and [S-13CH3] methionine; the labelling pattern supports the hypothesis that (1) is biosynthesized via the intramolecular Diels–Alder reaction.

Biosynthesis of ML-236C and the hypocholesterolemic agents compactin by Penicillium aurantiogriseum and lovastatin by Aspergillus terreus: determination of the origin of carbon, hydrogen and oxygen atoms by 13C NMR spectrometry and observation of unusual labelling of acetate-derived oxygens by 18O2

Sodium [1-13C, 2-2H3]-, [2-13C, 2-2H3]- and [1-13C, 18O2]-acetate are incorporated in separate experiments into ML-236C 2 and the hypocholesterolemic agent compactin 3 by cultures of Penicillium aurantiogriseum, and the regiochemical distribution of 2H, 13C and 18O is determined by 13C NMR spectrometry. In addition, sodium [1-13C, 18O2]acetate and 18O2 are incorporated into lovastatin (mevinolin) 4 by cultures of Aspergillus terreus to re-examine the origin of oxygen atoms. The results show that the main-chain oxygen atoms of 2–4 originate from acetate, and the C-8 oxygen atom of 3 and 4 is derived from molecular oxygen. However, detailed mass spectral analysis shows that significant amounts of aerobic oxygen can be incorporated at sites normally labelled by acetate oxygen, presumably through generation of [18O]acetate by ω-oxidation of fats. On the basis of labelling results, a mechanism is proposed to account for the formation of the bicyclic ring system in these compounds.

Metabolism of rishitin. The NIH-like shift in formation of rishitin M-2

Feeding experiments with (–)-[12,12-2H2]rishitin (1-D) in healthy potato tuber tissues indicated that metabolism of (1) into rishitin M-2 (3) proceeded with a stereospecific 1,2-migration of an olefinic hydrogen at C-12 of (1) in contrast with formation of rishitin M-1 (2) by direct oxygenation on C-13 of (1).