A modular tandem Michael or aza Michael approach to obtain indoline alkaloid-like polycyclic derivatives

Abstract

The use of small molecule chemical probes is highly attractive in dissecting complex biological processes (i.e. multiple protein-protein interactions and protein complexes-derived signaling networks) because of the probe's ability to induce subtle, and generally reversible, changes in protein dynamics. With the goal of developing new synthesis methods leading to high-throughput generation of natural product-like Indoline derivatives having different architectures, this thesis will highlight a modular, tandem reaction approach in which a key reaction is the use of a tandem Michael or aza-Michael reaction to obtain indoline alkaloid-like polycyclic architectures. An interesting feature is that the choice of an amino acid moiety in the side chain allowed the formation of different fused ring systems. The solution phase synthesis method was then developed on solid phase with an objective of generating few analogs in a high-throughput manner.