Olefin Metathesis in Peptidomimetics, Dynamic Combinatorial Chemistry, and Molecular Imprinting

摘要

Catalyzed based olefin metathesis is a very valuable and useful tool in synthetic organic chemistry. Our research goals consisted of employing olefin metathesis in the synthesis of peptidomimetics, and studying the feasibility of this method in dynamic combinatorial chemistry and molecular imprinting of nerve agents. One of the approaches to the development of peptidomimetics is to attach biologically significant functional groups, such as amino acid side chains, to a scaffold. Grubbs' second generation ruthenium catalyst was used to couple phenylalanine to a 17- membered lactam using cross- metathesis in 48% yield with an E:Z ratio of 1.2:1. The CM product of two phenylalanine amino acids was isolated in 45% yield and found to be predominantly trans. A series of synthetic steps were needed to construct the 17- membered lactam, including the fundamental RCM reaction. The reversibility of the cross metathesis of this macro cyclic system was demonstrated, which is essential to the development of a dynamic combinatorial library.