Biomimetic total synthesis of the pentacyclic Amaryllidaceae alkaloid derivative gracilamine

The illustrated azomethine ylide, produced through a Schiff base condensation of the corresponding aldehyde-containing C3a-arylhexahydroindole with ethyl l-leucinate, engages in a stereoselective intramolecular cycloaddition reaction to give adduct 23 that has been elaborated, over eight steps, into the racemic modification of the alkaloid derivative gracilamine (1). The formation of this ylide and its conversion into isomer 23 mimics the proposed biogenesis of the pentacyclic framework of compound 1.We thank the Australian Research Council and the Institute of Advanced Studies for financial support. N.(Y.)G. is the grateful recipient of a Postgraduate Award provided by the ANU. Dr Benoit Bolte (ANU) is warmly thanked for his invaluable advice throughout the duration of this project