Asymmetric synthesis of unusual amino acids: Synthesis of optically pure isomers of N-indole- (2-mesitylenesulfonyl)-β-methyltryptophan

Abstract

We have developed methods for the synthesis of the four optically pure isomers of β-methyltryptophan with the 2-mesitylenesulfonyl indole protecting group for peptide synthesis. Starting from 3-indoleacrylic acid, the β-methyl function was generated by a chiral auxiliary-directed asymmetric conjugate 1,4-addition. Asymmetric bromination was achieved via a tandem addition of N-bromosuccinimide to the enolate formed by the conjugate addition. Displacement of the bromide by azide, hydrolysis of the chiral auxiliary and then reduction, led to the two erythro isomers. Chiral imide enolate azidation of the conjugate adduct, hydrolysis of the chiral auxiliary and reduction yielded the two threo isomers in high optical purity.