Abstract
The stereochemistry of a novel Ca2+ antagonist, semotiadil, 1, was investigated using X-ray crystallography and CD. The X-ray structure was analyzed using its diastereomeric salt with (S)-(+)-mandelic acid (2); 1 (mandelate). The R absolute configuration of 1, which was previously determined by chemical transformation of the optically-active synthetic precursor, was directly confirmed by this analysis. The hydrogen bonding, electrostatic and the hydrophobic interactions, which stabilize the crystal structure, were observed in the crystal. CD spectra of 1 (mandelate) and the hydrogen fumarate of 1 (SD-3211; 1 (fumarate)) in ethanolic solution exhibited similar spectral patterns. The CD bands from each chromophore were unambiguously assigned and the conformation of the benzothiazine ring was determined using the helicity rule. The X-ray and CD data confirmed the P-conformation of the benzothiazine ring and the existence of the 2-phenyl ring in an equatorial position in both of the crystal and ethanolic solution states. These findings were in good agreement with our previous results regarding the conformational analysis of 2-arylbenzothiazine derivatives.
