This proposal explores the use of tryptophan as a starting material for the total synthesis of ergot alkaloids. The methods involve intramolecular Friedel-Crafts reaction of a suitably protected tryptophan to give an optically active tricyclic skeleton ideally functionalized for elaboration to natural products. Either enantiomer is available from L-tryptophan. Specific targets include the ergolines lysergene and lysergol, the chanoclavines and clavicipitic acid. The latter involves a study of intramolecular amido-alkylation of the 4-position of tryptophan from which substances of biosynthetic interest should become available. Finally, a mechanistic study of the peculiar racemization and isomerization behavior of the rugulovasine ergot alkaloids is proposed.
