Cinchona alkaloids:: the structure of β-isocinchonicine revisited

Analysis of beta -isocinchonicine - the enolo-ethereal derivative of cinchonine - by NMR, AM1 calculations, and X-ray diffraction resulted in the assignment of its structure as 1(S)-ethyl-3-(quinol-4-yl)-2-oxa-6(S)-9-azabicyclo[4,4,0]dec-3-ene contrary to the structure with seven-membered enolo-ethereal ring reported in the literature. The AM 1 calculations also showed several energetically favorable conformations with the ethyl group equatorial in relation to the piperidine fragment. Four of these forms (II,V,VIII,XI), supported by NOEs and being the rotamers of the quinolyl and ethyl substituents, are most probable components of the conformational equilibrium mixture of beta -isocinchonicine. Three of the rotamers have been observed by Xray diffraction: two in the crystals of beta -isocinchonicine hydroiodide monohydrate (7 . HI .H2O) are linked into an asymmetric dimer by a pair of N-HN+ hydrogen bonds and another rotamer in its hydroiodide dihydrate (7 . HI . 7H(2)O) where the cations are linked by N-HN+ hydrogen bond into helices. (C) 2001 Elsevier Science B.V. All rights reserved.