Three putative intermediates in the biosynthesis of the lipase inhibitor lipstatin were synthesized in stable isotope-labeled form and were added to fermentation cultures of Streptomyces toxytricini. Biosynthetic lipstatin was isolated and analyzed by NMR spectroscopy.[3, 10, 11, 12-2H]-(3 S, 5 Z, 8 Z)-3-hydroxytetradeca-5, 8-dienoic acid (9) was shown to serve as a direct biosynthetic precursor of lipstatin.[7, 8-2H2] Hexylmalonate (11) ...
