First Total Synthesis of the Pyrrolizidine Alkaloid Amphorogynine C through Intramolecular Azide-Olefin Cycloaddition

• Published in: European journal of organic chemistry 2012-08, Vol.2012 (23), p.4347-4353
• Main Authors: de Miguel, Irene, Velado, Marina, Herradón, Bernardo, Mann, Enrique
• Format: Article
• Language: English
• Subjects: Alkaloids; Azides; Chemistry; Condensed matter: structure, mechanical and thermal properties; Cycloaddition; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Natural products; Organic chemistry; Organic compounds; Physics; Preparations and properties; Structure of solids and liquids; crystallography; Structure of specific crystalline solids; Total synthesis
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201200384

The first total synthesis of the natural alkaloid amphorogynine C is reported (2.9 % overall yield in 20 steps). The key steps include a Claisen–Johnson rearrangement and an intramolecular azide–olefin cycloaddition, followed by a reduction of the resulting imine. The construction of the pyrrolizidine skeleton was achieved by an alkoxide‐mediatedlactone ring opening and subsequent cyclization of a conveniently functionalized bicyclic amine. Finally, the proposed structure of amphorogynine C was confirmed by single‐crystal X‐ray diffraction analysis. The first synthesis of the representative pyrrolizidine alkaloid amphorogynine C is described. The key step includes an intramolecular azide–olefin cycloaddition reaction. The proposed structure of the natural product was confirmed by single‐crystal X‐ray diffraction analysis.