Norhygrine Alkaloid and Its Derivatives: Synthetic Approaches and Applications to the Natural Products Synthesis

Abstract

This review summarizes the advances in the synthesis of norhygrine and its derivatives over the past ten years, with special attention paid to stereoselective methods of their preparation. Information on the biological activity of some derivatives of 1-(pyrrolidin-2-yl)propan-2-one is presented and the possibility of using pyrrolidines containing a terminal carbonyl group in the synthesis of various alkaloids with useful properties is shown.

Enamine-mediated Mannich reaction of cyclicN,O-acetals and amido acetals: the multigram synthesis of pyrrolidine alkaloid precursors

“…These 2-substituted pyrrolidines can be further transformed into various pyrrolidine, indolizidine, and tropane alkaloids. 3 In nature, these pyrrolidine alkaloids are synthesized through the enzyme-catalyzed Mannich-type reaction between enolates derived from acetyl-CoA or acetoacetyl-CoA and the 1-pyrrolinium cation as a key carbon-carbon bond-forming step. 4 Conceptually, this strategy was first implemented in laboratory synthesis by Ritchie and coworkers, who reported the formation of cuscohygrine from 4-(methylamino)butanal and 3-oxobutanoic acid in neutral media via transient cyclic hemiaminal, although no experi-mental details were given.…”