Pyrrolizidine alkaloids necine bases: II. Conformational analysis of free bases

Abstract

Molecular mechanics calculations were applied to the conformational analysis of two diasteroisomers, the pyrrolizidine alkaloids (PAs) retronecine and heliotridine. The application of reoptimized parameters for H bonding corrected the tendency of MM3(92) calculations to give unrealistic H(DOTTED BOND)O distances for intramolecular OH interactions occurring in both diasterisomers. Inversions in the H‐bond direction of exo‐retronecine and in the relative stability of heliotridine endo–exo conformers were also observed with the application of the new parameters. A set of probable conformers was obtained for each diasterisomer, based on conformational and Boltzmann population analysis. Only exo‐puckered conformers were found in the retronecine set, whereas both exo‐ and endo‐puckered conformers were obtained for heliotridine. Transition state conformations supplied arguments supporting the design of models for H‐bond interconversion in the case of exo‐retronecine and for the exo–endo interconversion of heliotridine. Reactivity behaviors and 1H‐NMR data of both diasterisomers were elucidated in light of the theoretical results. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1853–1861, 1998

Pyrrolizidine alkaloids (July 1998 to June 1999)

“…36 A new molecular mechanics conformational analysis of retronecine and heliotridine using re-optimised parameters has been carried out, and the theoretical results used to elucidate the observed reactivity and 1 H NMR data for the necines. 37 The synthetic pyrrolizidine 137 has been successfully employed as a chiral catalyst in the Baylis-Hillman reaction. 38 Collisioninduced dissociation HPLC/MS has been used to detect two different types of hepatotoxic pyrrolizidines as well as to differentiate between toxic and non-toxic pyrrolizidines.…”