X-Ray Structural Investigation of the Chiral Recognition of Brucine in Salt Formation with an N-Protected Amino Acid, N-Phthaloyl-threo-β-hydroxy- d - and l -leucine

In order to determine how brucine recognizes the chirality of an N-protected amino acid in complex formation, three kinds of brucine complex crystals of N-phthaloyl-threo-β-hydroxyleucines, i.e., two (yellow and transparent) crystals for the l-isomer and one (transparent) crystal for the d-isomer, were prepared, and their structures were determined by X-ray crystallography. In addition to the interaction mode specific for each complex crystal, the carboxyl and β-hydroxyl groups of the amino acids were commonly linked with the methoxyindole and piperidine ring moieties of brucine through hydrogen bonds and electrostatic and van der Waals interactions. In addition to the direct interactions between the molecules, the molecular arrangement of brucine in the crystal structure played an important role in the d/l-recognition of the amino acids. The molecular packing of the brucine molecules translated by a crystallographic 2-fold screw symmetry operation provided a shape for the cavity that was most suitable for binding with the d-isomer. In contrast, two crystallographically independent brucine molecules participated in recognizing the l-isomer, where the arrangement of these molecules in the crystal structure formed a receptor surface suitable for binding with the l-isomer. In this paper, an explanation of how brucine recognizes the d/l-isomer in the crystalline state is presented.