Ergoline system biosynthesis

Incorporation of label from [2- " C]mevalonate into the ergoline ring system supported the hypothesis that the pathway involved aromatic prenylation 68). This was further supported by the identification and purification of tryptophan dimethylallyltransferase 69,70), which transferred the dimethylallyl moiety from dimethylallyl-diphosphate (DMAPP) to the 4-position on the six-membered ring of L-tryptophan. Molecular genetic studies confirmed the role of this enzyme in EA biosynthesis 39,54). 

To elucidate further the mechanism of closure for ring C, Floss et al. synthesized the racemic amino acid shown in Scheme 58 [88]. Feeding experiments with the N-trideuteriomethyl labeled compound showed a 33% specific incorporation of the amino acid into elymoclavine. The high level and specificity of incorporation (no M-i-1 or M-i-2 species were detected) clearly point toward the intermediacy of the tertiary carbinol in the biosynthesis of the tetracyclic ergoline ring system. On the basis of these results. Floss et al. proposed the overall sequence shown in Scheme 53 for elaboration of the C ring system [88]. 

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