SYNTHESIS AND STRUCTURAL, BIOCHEMICAL, AND PHARMACOLOGICAL STUDY OF 3-BETA-ACYLOXY-3-ALPHA-METHOXYCARBONYLTROPANE DERIVATIVES

A series of 3beta-acyloxy-3alpha-methoxycarbonyltropanes were synthesized and studied by H-1 and C-13 NMR spectroscopy, and the crystal structure of 3alpha-methoxycarbonyl-3beta-pyridincarbonyloxytropane (5d) was determined by X-ray diffraction. In CDCl3 solution, compounds 5a-f display the same preferred conformation. The pyrrolidine and piperidine rings adopt an envelope conformation flattened at N-8 and a distorted chair conformation puckered at N-8 and flattened at C3, respectively, with the N-substituent in the equatorial position with respect to the piperidine ring. The pharmacological profile of one of these compounds makes it an adequate candidate for the design of novel GABA(B) antagonist agents.