PYRROLIZIDINE ALKALOIDS NECINE BASES - AB-INITIO, SEMIEMPIRICAL, AND MOLECULAR MECHANICS APPROACHES TO MOLECULAR-PROPERTIES

The structural stabilities of endo and exo conformations of retronecin e and heliotridine molecules were analyzed using different ab initio, semiempirical, and molecular mechanics methods. All electron and pseud opotential nb initio calculations at the Hartree-Fock level of theory with 6-31G and CEP-31G* basis sets provided structures in excellent a greement with available experimental results obtained from X-ray cryst al structure and H-1-NMR (nuclear magnetic resonance) studies in D2O s olutions. The exo conformations showed a greater stability for both mo lecules. The most significant difference between the calculations was found in the ring planarity of heliotridine, whose distortion was asso ciated with the interaction between the O(11)H group and the C(1)-C(2) double bond as well as with a hydrogen bond between O(11)H and N(4). The discrepancy between pseudopotential and all-electron optimized geo metries was reduced after inclusion of the innermost electrons of C(1) , C(2), and N(4) in the core potential calculation. The MNDO, AM1, and PM3 semiempirical results showed poor agreement with experimental dat a. The five-membered rings were observed to be planar for AM1 and MNDO calculations. The PM3 calculations for exo-retronecine showed a great er stability than the endo conformer, in agreement with ab initio resu lts. A good agreement was observed between MM3 and nb initio geometrie s, with small differences probably due to hydrogen bonds. While exo-re tronecine was calculated to be more stable than the endo conformer, th e MM3 calculations suggested that endo-heliotridine was slightly more stable than the exo form. (C) 1996 by John Wiley & Sons, Inc.