Modular Approach in Synthesis of Polycyclic Indolizidine, Quinolizidine, and Related Alkaloids

Abstract

Indolizidine and quinolizidine alkaloid natural products and their analogs possess structural diversity and complexity along with a broad range of biological and medicinal properties, which make them attractive targets to synthetic chemists. A great deal of effort on retrosynthetic design and the execution of various synthetic routes toward these molecules have made significant contributions to the advancement in both organic synthesis and medicinal chemistry in the past decades. Herein, we discuss selected reported syntheses (2002–2024) of quinolizidine, indolizidine, and related alkaloids. Starting from pyrrolidine and piperidine equivalents as building blocks, we focus on a modular approach in which subunits are combined in a convergent fashion leading to synthetic efficiency. We place emphasis on targets with tricyclic, tetracyclic and higher order polycyclic indolizidine, quinolizidine, and related alkaloids to showcase the efficiency of these modular approaches for the synthesis of the natural products and their analogs with these privileged molecular frameworks.