A Bridge to Alkaloid Synthesis

Abstract

The construction of a structurally rigid architecture with chiral complexity, necessary to enhance the interaction with binding sites of drug targets, has been adapted as an intriguing approach in drug development. In the past few years, we have been interested in the synthesis of biologically significant and bridged alkaloids via novel synthetic methods and strategies based on recognition of the privileged pattern. Therefore, nitroso-ene and aza-Wacker cyclizations were elevated for the first time to construct bridged alkaloids, such as hosieine A, kopsone, melinonine-E and strychnoxanthine. Mechanistic investigations, including computational calculations for nitroso-ene reaction and deuterated experiments for aza-Wacker reaction, enable us to gain more insights into the chemical reactivity and selectivity of specific functional groups in developing viable synthetic methods.

Keywords: Mannich; alkaloid; aza-Wacker; nitroso-ene; total synthesis.