Biosynthesis of trichothecenes and apotrichothecenes

Fusarium culmorum produces two major trilchothecenes, 3-acetyldeoxynivaleno l and sambucinol, and some minor apotrichothecenes. It was desired to inves tigate if during their biosynthesis a C-11-keto intermediate was involved. To verify this postulate, trichodiene, a known precursor to trichothecenes, was synthesized with two deuteriums at C-11 and one at C-15. It was then f ed to F. culmorum cultures, and the derived metabolites were purified and a nalyzed. The results ruled out the involvement of an 11-keto intermediate b ut revealed two novel apotrichothecenes. The characterization of their stru ctures suggested that one of the 2-hydroxy-11 alpha-apotrichothecene stereo isomers (2 alpha or 2 beta) could be converted to sambucinol. These apotric hothecenes were therefore synthesized labeled specifically with two deuteri ums at C-4 and C-15 and fed to F. culmorum cultures. Indeed, the result est ablished for the first time that 2 alpha-hydroxy-11 alpha-apotriehothecene was a precursor to sambucinol. A biosynthetic scheme for the production of trichothecenes and apotrichothecenes is described.