Efforts towards the total synthesis of natural product alkaloids (+/-) lycorine and gracilamine, gold-catalyzed diene formation, and oxy-Ccope/ene/Claisen/Diels-Alder reactions to form the homo-steroid skeleton.

摘要

The amaryllidaceae family is an attractive source of alkaloids, which are valuable targets for total synthesis. This thesis describes the ingenious approach to the synthesis of two amaryllidaceae alkoids: (+/-)-lycorine and gracilamine. Utilization of the phenylbutadiene and pyrroline intramolecular push-pull Diels-Alder reaction for lycorine and of the intramolecular 1,3-dipolar cycloaddition for gracilamine is described. A route was developed to give access to advanced intermediates required for both syntheses. However the existing methodology did not fully accommodate the complete core structure of the targets.;Finally, we investigated the 1-alkynyl-2-vinyl-cyclohexanols for the formation of multi-cyclic skeletons found in natural products. Our goal was to develop a way to easily access the steroid and/or carbocyclic core in one tandem reaction sequence. To this end, the use of a tandem oxy-cope/Claisen/ene/Diels-Alder reaction was developed. The tandem oxy-Cope/ Claisen/ene/Diels-Alder reaction can produce up to 9 contiguous stereogenic centers where two are quaternary. In addition, this domino process provides the steroid core possessing much exploitable functionality.;Development of a new novel gold-catalyzed reaction is also depicted. A facile and quick method to generate dienes from propargylic acetates and pyvaloates has been developed. The scopes and limitations of this methodology are discussed. The application of the newly discovered Au(PPh3)Cl and acid catalyst system was examined.