A unique approach to the concise synthesis of highly optically active spirooxazolines and the discovery of a more potent oxindole-type phytoalexin analogue

Abstract

Drug-lead synthesis through rapid construction of chiral molecular complexity around the biologically relevant framework using a highly efficient strategy is a key goal of organic synthesis. Molecules bearing a spirooxindole-type framework exhibit important bioactivities. Herein, we present a highly efficient and convenient strategy that allows rapid construction of unique optically active spiro[oxazoline-3,3'-oxindole]s through the organocatalyzed asymmetric synthesis of spirocyclic thiocarbamates via an aldol reaction. Preliminary biological evaluation of several of the spirooxazolines using a model of acute neuroinflammation revealed promising antipyretic activity and provided an opportunity to discover new antipyretic agents.