THE SYNTHESIS OF PYRROLIZIDINE ALKALOIDS

• Main Author: NEUENSCHWANDER, KENT WILLIAM
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-1982
• Subjects: Organic chemistry
• ISBN: 9798790692239

The pyrrolizidine alkaloids constitute an exceptionally large class of naturally occurring compounds. A number of the alkaloids are hepatotoxic and carcinogenic, but some derivatives have potentially useful physiological properties. A promising but seldom used reaction in alkaloid synthesis is the amidoalkylation of enolizable carbonyl derivatives. The reaction involves electrophilic attack on the enol by an (alpha)-acyliminium ion. This results in formation of a new carbon-carbon bond (alpha) to the nitrogen. This potentially useful reaction was used for the synthesis of several pyrrolizidine alkaloids. The simple pyrrolizidines, trachelanthamidine and isoretronecanol, were prepared from succinimide. The synthesis required only five steps and proceeded in good overall yield. The synthesis is the most direct and operationally convenient route yet reported. An intermediate for the synthesis of heliotridine was also prepared. The synthetic route gave good stereochemical control of the key asymmetric centers. Completion of the synthesis requires only reduction of a methyl ester and removal of a mesityl protecting group.