Biogenesis of the Ergot Alkaloids

In all hypotheses relating to the biogenesis of the ergoline-lysergic acid moiety of ergot alkaloids, it was assumed that tryptophan constituted a main structural element. This assumption was later shown by experiment to be correct. 

In saprophytic cultures of the Pennisetum ergot fungus, only tryptophan, deuterated in the 5 or 6 position, was used for the synthesis of the clavine alkaloids without loss of the deuterium. Deuterium in the 4 position was lost. These experiments showed that the hypotheses, according to which 5-hydroxytryptophan would be an intermediate stage in the biosyntheses (126, 127), could not be correct (128). 

Various hypotheses were forwarded concerning the nature of the structural element which was required in biosynthesis in addition to the tryptamine portion (127, 126, 129, 130). The following experiments show that, aside from tryptophan, an isoprenoidal 5-C compound participates in the formation of the ergoline structure. This was first postulated by Mothes (121). 

Mevalonic acid, the precursor of the active isoprene, was used in the incorporation studies. Both mevalonic acid-2-C14 and mevalonic acid-2T or -4T were utilized by the fungus for the synthesis (131, 132). By means of a stagewise degradation of radioactive alkaloids formed with the aid of mevalonic acid-2-C14 and localization of the C14, it could be shown that mevalonic acid is incorporated into the molecule in the manner depicted by the accompanying reaction scheme (133, 134, 135). 

The addition of mevalonic acid-l-C14 to a pyroclavine- and festuclavine-producing fungus strain yielded inactive alkaloids which, in agreement with the scheme, showed that the carboxyl group of the mevalonic acid is not incorporated. Lowering of the assimilation of mevalonic acid-2-C14 by the addition of dimethylallylpyrophosphate or isopentenylpyrophos-phate supported the assumption that mevalonic acid enters the alkaloid molecule via one of these activated isoprene radicals. This was confirmed by the incorporation of deuterated isopentenylpyrophosphate in alkaloids of the clavine type in saprophytic cultures of a Claviceps strain (128). 

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TLC has been applied to studies of chemical reactions of ergot alkaloids [90, 223] the configuration of lysergic acid [224] biogenesis of the ergot alkaloids [79, 80, 140] pharmaceutical preparations [68]. 

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