Probing Ergot Alkaloid Biosynthesis: Intermediates in the Formation of Ring C

The mode of C-ring formation in ergot alkaloid biosynthesis was probed by synthesizing two potential intermediates, compounds 6 and 7, in deuterated form from the prenylated indole 8. Both compounds were incorporated into the ergot alkaloid elymoclavine by washed mycelia of Claviceps sp., strain SD 58, but only the formation of 7, and not 6, could be demonstrated in the cultures. Hence it is proposed that only 7 is an intermediate in ergot alkaloid biosynthesis, whereas 6 is not on the pathway but can be converted into 7 when added to the cultures. A pathway is proposed for the formation of ring C involving epoxidation of 7 at the terminal double bond and cyclization of the epoxide with simultaneous decarboxylation.