PATRICIA ECIJA, EMILIO J. COCINERO, FRANCISCO J. BASTERRETXEA, JOSÉ A. FERNANDEZ, FERNANDO CASTANO, Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco (UPV/EHU), Ap.644, E-48940, Bilbao, Spain; ALBERTO LESARRI, Departamento de Química Física y Química Inorgánica, Facultad de Ciencias, Universidad de Valladolid, E-47011 Spain.

Tropane alkaloids have diverse pharmacological uses and are well-known for their neurostimulant activity. Previous structure-activity-relationship established correlations between bioactivity and several aspects of ligand conformation and stereochemistry, including delicate intramolecular effects like nitrogen inversiona. We have initiated a series of structural studies on tropane alkaloidsb, aimed to discerning their intrinsic stereochemical properties using rotational spectroscopy in supersonic jetsc. Here we extend these studies to the epoxytropanes, initially motivated to interrogate the influence of the epoxy group on nitrogen inversion and ring conformation. The rotational spectrum evidences a single structure in the gas phase, providing a first description of the (three ring) structurally-distorted tropane in scopoline. The determined rotational parameters of scopoline reveal the structural consequences of the intramolecular cyclation of scopine, which breaks the original epoxy group and creates a new ether bridge and a 7 beta-hydroxytropane configuration. The hydroxyl group further stabilizes the molecule by an O-H cdots N intramolecular hydrogen bond, which, in turn, forces the N-methyl group to the less stable axial formb. The experimental work was supported by ab initio and DFT calculations.

a i) S.Singh, Chem. Rev. 100, 925 (2000); ii) A. Krunic, D. Pan, W.J. Dunn III, S.V.S. Miariappan, Bioorg. & Med. Chem. 17, 811 (2009).
b E.J. Cocinero, A. Lesarri, P. Écija, J.-U. Grabow, J.A. Fernández, F. Castaño, Phys. Chem. Chem. Phys. 12, 6076 (2010).
c E.J. Cocinero, A. Lesarri, P. Écija, J.-U. Grabow, J.A. Fernández, F. Castaño, Phys. Chem. Chem. Phys. 12, 12486 (2010).