Chiral Selectivity in the Achiral Amino Acid Glycine

A Cambridge Structural Database (CSD) search for the zwitterion of glycine, the only natural amino acid which does not have a chiral center at C-alpha, and its derivatives H3N-C alpha H-2-C'(O-cis)O-trans(H/R/M) gave 425 hits, 420 of which are chiral because of the psi conformation with regard to the central C'-C-alpha bond (psi = OcisC'C alpha N not equal 0 or 180 degrees). Chiral psi conformations distort the planar carboxylic group C alpha C'(O-cis)O-trans group stereoselectively to an asymmetric flat tetrahedron with four different corners, specified by (R-theta)/(S-theta). Negative rotation angles psi predominantly induce pyramidalization angles theta = O-trans -C'-C alpha Ocis below -180 degrees, resulting in a high diastereoselectivity for (M-psi,S-theta)-glycine. Positive rotation angles psi preferentially give (P-psi,R-theta)-glycine. Density functional theory calculations confirm the results of the data analysis, indicating an increase of pyramidalization theta for increasing rotation angles psi. This is corroborated by the analysis of section averages of the structural data, showing an increase of the psi/theta selectivity in the series 1.5, 2.8, 3.5, and 6.0 for increasing rotation angles psi. Without any chiral bias, 419 glycine derivatives crystallize in the ratio racemate/conglomerate 359:65.