Synthesis and Structural, Biochemical, and Pharmacological Study of 30-Acyloxy-3a-methoxycarbonyltropane Derivatives

A series of 3β-acyloxy-3α-methoxycarbonyltropanes were synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 3α-methoxycarbonyl-3/3-pyridincarbonyloxytropane (5d) was determined by X-ray diffraction. In CDCI3 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 GABAB antagonist agents.