BIOSYNTHETIC INTERMEDIATES OF INDOLE-DITERPENOID MYCOTOXINS FROM SELECTED TRANSFORMATIONS AT C-10 OF PAXILLINE

The products of NaBH4 reduction of the 10-keto group of paxilline, bio synthetically radiolabelled with C-14 in the diterpenoid moiety, resol ved into alpha and beta isomers, were fed to submerged fermentations o f Penicillium janczewskii and P. janthinellum producing penitrem and j anthitrem alkaloids, respectively. Incorporation into the alkaloids wa s compared with that of [C-14]paxilline, 13.7 and 23.2% of which was f ound in penitrems and janthitrems, respectively. 10beta-Hydroxy[C-14]p axilline (beta-paxitriol) was incorporated 10.7% into penitrems and 34 .5% into janthitrems, providing compelling evidence that both paxillin e and its 10beta-hydroxy derivative are intermediates in the biosynthe sis of these aromatic-substituted indole-diterpenoids. Low (approximat ely 1%) incorporation values for 10alpha-hydroxy[C-14]paxilline (alpha -paxitriol) indicated that this isomer is not an intermediate but that the fungi, particularly P. janthinellum, may possess some isomerase a ctivity. 10beta-O-Acetyl[C-14]paxilline was incorporated (4.5%) into j anthitrems B and C, probably via deacetylation to beta-[C-14]paxitriol . 10alpha-O-Acetyl[C-14]paxilline was not significantly incorporated.