Catalytic Asymmetric Approach to the Naturally Occurring Clavine Alkaloid (+)-Lysergine

This work is dedicated respectfully to Prof. H. Ila, JNCASR Bangalore, India.

Abstract

An efficient asymmetric approach to the ergot alkaloids has been achieved via a highly regioselective Heck cyclization. Asymmetric induction of the key intermediate was achieved via a catalytic enantioselective α-aminoxylation catalyzed by d-proline (98% ee). Utilizing the aforementioned strategy, formal total synthesis of the ergot alkaloids (+)-lysergine and (+)-isolysergine has been achieved. Importantly, an asymmetric approach to the unnatural analogues (–)-lysergine and (–)-isolysergine has also been achieved via catalytic enantioselective α-aminoxylation using l-proline.

Key words

asymmetric total synthesis - regioselective Heck cyclization - lysergine - α-aminoxylation - ergot alkaloids

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