Synthesis of 5,5 di-Substituted gamma- Lactams through a Base Mediated Molecular Rearrangement

Abstract

This project is mainly focusing on the design and synthesis of gamma-lactams starting from simple amino acids. The gamma-lactams are important components of many drugs. The gamma-lactams reported here is different from the lactams reported in the literature. These gamma-lactams have been derived from the alpha, beta-unsaturated gamma-amino amides. All unsaturated amino acids have been synthesized by Wittig reaction using N-protected amino aldehydes. Amino aldehydes have been synthesized from IBX oxidation of amino alcohol. All amino alcohols have been synthesized through the reduction of NHS active esters of amino acids. These alpha, beta unsaturated gamma-amino amides are transformed into gamma-lactams through a new rearrangement mediated by the base KOBut. The excellent feature of this process is that it is possible to introduce three different amino acid side-chains on a simple gamma lactam. The main focus of this project is that explore these molecules as inhibitors of protein-protein interactions, particularly p53-MDM2 interactions