Abstract

Diverse Synthesis of Natural Product Inspired Fused and Spiro-Heterocyclic Scaffolds Via Ring Distortion and Construction Strategy

Subhabrata Sen, Associate Professor, Shiv Nadar University

An efficient domino Pictet-Spengler lactamization (PSL) generated nine indole based fused scaffolds which are inspired from natural products.1 Facile functional group transformation, ring distortion and ring construction approach on few of them afforded another seven scaffolds. Starting from simple raw materials like tryptamine and D/L-tryptophan, this synthetic strategy with steps/scaffold ratio of 1 is extremely efficient in building the scaffold library containing six disparate architectures. In vitro screenings of this library against MCF-7 cell lines resulted in two active scaffolds that could moderately inhibit the proliferation of MCF-7 cells. Principal component analysis of this library against a natural product and commercial drug database indicated an eclectic mix of structures among the molecules. During the course of the investigation the first ever organocatalytic domino PSL reaction was demonstrated with a thiourea catalyst.