Toward diversity-oriented synthesis of indoline-based polycyclic derivatives

Abstract

There is a growing interest in using diversity-oriented synthesis (DOS) to generate small molecule libraries that are inspired by bioactive natural products. Over the years they have proven to be quite valuable chemical probes for understanding protein functions. Of particular interest is the design of natural product-like chiral scaffolds in which one could explore the three dimensional space around the building block by having several chiral diversity sites. A novel synthesis to reach an indoline scaffold is described. This template is then utilized to synthesize a seven-membered ring tricyclic derivative through an olefin ring-closing metathesis (RCM) approach. As well, asymmetric diversity-oriented reactions (e.g. asymmetric benzenethiol addition and intramolecular free radical cyclization) were explored with the tricyclic compound with the intention of utilizing these reactions on solid phase for generating a library.