Comparison of Fatty Acid and Polyketide Biosynthesis: Stereochemistry of Cladosporin and Oleic Acid Formation in Cladosporium cladosporioides

Article abstract of DOI:10.1021/ja00191a041

Stereochemical aspects of the biosynthesis of the polyketide cladosporin (1) and of oleic acid (2) by Cladosporium cladosporioides NRRL 5507 were compared by use of stable isotope labeling and 2D NMR spectrometry.The absolute stereochemistry of 1 was confirmed by degradation to (2R,6S)-(-)-(6-methyltetrahydropyran-2-yl)acetic acid (12).Incorporations of sodium <1-(13)C>-, <2-(13)C>-, <1,2-(13)C2>-, <1-(13)C,(18)O2>-, <1-(13)C,(2)H3>-, and <2-(13)C,(2)H2>acetates into 1 followed by (13)C NMR analysis of its diacetate 13 provided the biosynthetic pattern of all bonds derived intact from acetate.Deuterium-decoupled (1)H,(13)C shift correlation NMR spectra of 13 derived from <2-(13)C,(2)H3>acetate showed that deuterium occupies the pro-R position at C-9 and the pro-S position at C-11.Oleic acid (2) obtained from the same incorporation experiment was degraded and derivatized with methyl (S)-(+)-mandelate to afford esters 20 and 21a.Stereospecifically deuterated standard samples 21b and 21c were synthesized.Deuterium-decoupled (1)H,(13)C shift correlation NMR spectra of these compounds demonstrated that during fatty acid biosynthesis in C. cladosporioides the intact carbon-hydrogen bond of acetate is in the pro-R position, the opposite of that at C-11 for the polyketide 1.The possible mechanism of tetrahydropyran ring formation during biosynthesis of cladosporin (1) is discussed.