Reactive intermediates in peptide synthesis. Molecular and crystal structures of reactive carboxylic amides

Abstract

Abstract The molecular and crystal structures of N-para-toluenesulphonyl-N-methyl-α-aminoisobutyric acyl imidazole (1), and 3-(N-para-toluenesulphonyl-α-aminoisobutyric acyl)-1,3-thiazolidine-2-thione (2) have been determined by X-ray diffraction. Crystal parameters: (1) orthorhombic, space group P212121, a = 11.735(2) Å, b = 19.990(3) Å, c = 6.925(1) Å, and Z = 4; (2) orthorhombic, space group Pnc2, a = 9.507(2) Å, b = 16.902(2) Å, c = 10.347(2) Å, and Z = 4. The structures were solved by direct methods. The least-squares refinements led to conventional R factors of 0.036 and 0.031 for (1) and (2), respectively. This is the first geometrical and conformational characterization at atomic resolution of N α -protected α-aminoacids containing the elusive acyl imidazole and 3-acyl-1,3-thiazolidine-2-thione C-activating groups. Only the reactive carboxylic amide of (2) deviates significantly from planarity.