Pseudo-enantiomeric coupling reagents for predictable incorporation into the peptide chain D and/or L amino acid residue of racemic substrates

Abstract

Reaction of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) with bis-tetrafluoroborates of quinine and/or quinidine in the presence of sodium bicarbonate gave a pair of pseudo-enantiomeric coupling reagents: N,N'bis-(4,6-dimethoxy-1,3,5-triazin-2-yl)quinine bis-tetrafluoroborate (2DMT/quinine/2BF4 -) and N,N'-bis-(4,6dimethoxy-1,3,5-triazin-2-yl)quinidine bis-tetrafluoroborate (2DMT/quinidine/2BF4 -). The reagents activate the opposite enantiomers of racemic N-protected amino acids. By their reaction with two equivalents of racemic carboxylic components and diverse esters of amino acids, protected dipeptides were obtained with a predictable configuration and 95-99% enantiomeric homogeneity.