Cinchona alkaloids: the structure of beta-isocinchonicine revisited

Analysis of beta -isocinchonicine - the enolo-ethereal derivative of cincho nine - by NMR, AM1 calculations, and X-ray diffraction resulted in the assi gnment of its structure as 1(S)-ethyl-3-(quinol-4-yl)-2-oxa-6(S)-9-azabicyc lo[4,4,0]dec-3-ene contrary to the structure with seven-membered enolo-ethe real ring reported in the literature. The AM 1 calculations also showed sev eral 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 substit uents, are most probable components of the conformational equilibrium mixtu re of beta -isocinchonicine. Three of the rotamers have been observed by Xr ay diffraction: two in the crystals of beta -isocinchonicine hydroiodide mo nohydrate (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.