Total Synthesis of (+)-nemorensic acid: En Route to (-)-callosine

Matthew R. Vriesen, The University of Western Ontario

Abstract

An intramolecular oxime ether cyclopropane annulation developed in 2008 by Kerr has been shown to form 2,5-trans and 2,5-cis pyrrolidines in a stereodivergent fashion. When the oxime ether is functionalized with an enantioenhanced α-hydroxy substitutent and a leaving group, the pyrrolizidine core of (-)-callosine can be accessed in short order. Callosine is a structurally unique pyrrolizidine alkaloid isolated from Mexican flowering plant Senecio callosus. In an effort to complete the total synthesis, the total synthesis of (+)-nemorensic acid, the necic acid component of the callosine, has been established. Attempts at appending the ansa bridge via esterification and macrolactonization are discussed.