Synthesis of Pyrrolo[2,1‐a]isoquinoline Class of Natural Product Crispine A

Abstract

AbstractAs a naturally occurring small‐molecule, various optical isomers of chiral pyrrolo[2,1‐a]isoquinoline alkaloid crispine A represent a potential class of chiral molecules in contemporary organic chemistry, and possess diverse biological activities. The range of pharmacological activities include antidepressant, antiplatelet, antileukemic, and anticancer activities. This review provides an overview of the literature on the strategies, employed in the synthesis of crispine A in their racemic and enantiopure forms via Bischler‐Napieralski cyclization, Pictet‐Spengler cyclization, N‐Alkylation/Acylation‐cyclization, Oxidative cyclization, and Asymmetric hydrogenation in the period of 1931–2021. This study accentuates the need for the developing more effective synthesis, and search for involved biological applications for the pyrroloisoquinoline class of natural product. Attention has been drawn towards the use of relatively less documented but easily accessible naturally occurring diastereomeric scaffolds namely, garcinia and hibiscus acids. These lactones obtained from (+)‐ and (−)‐2‐hydroxycitric acids bearing chemically amenable functional groups are investigated as an ideal choice for the enantiopure synthesis of the (−)‐(R)‐ and (+)‐(S)‐Crispine A structural frame work.