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

The first total synthesis of the natural alkaloid amphorogynine C is reported (2.9?% overall yield in 20 steps). The key steps include a ClaisenJohnson rearrangement and an intramolecular azideolefin 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.