Practical, asymmetric synthesis of aromatic-substituted bulky and hydrophobic tryptophan derivatives

An efficient method for the synthesis of novel aromatic Substituted, bulky and hydrophobic tryptophan derivatives has been developed. Asymmetric hydrogenations of alpha -enamide 5 using Burk's DuPHOS-based catalysts generated high enantiomerically pure D- and L-alpha -amino acid derivatives 6, which subsequently underwent Suzuki cross couplings with boronic acid derivatives to afford aromatic substituted tryptophan derivatives 7 and 8 in high yields. The method can allow for the preparation of such amino acids in large-scales for extensive structure-activity studies. (C) 2001 Elsevier Science Ltd. All rights reserved.