Molecular mechanics studies of a-and B-Azabicyclane opiates using the amber forcefield

• Main Author: Gacho, Eduardo H.
• Format: text
• Language: English
• Published: Animo Repository 1997
• Subjects: Molecular structure; Force and energy; Mechanics; Alkaloids > Spectra; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/etd_masteral/1732; https://animorepository.dlsu.edu.ph/cgi/viewcontent.cgi?article=8570&context=etd_masteral
• Institution: De La Salle University

Empirical forcefield calculations are performed on the diasteriomeric a- amd B- azabicyclanes (3-methyl-9-methoxy-9-phenyl-3-azabicyclo[3.3.3] nonames), which are prototypical phenyl-axial and phenyl-equatorial opiates. After energy minimization, optimized structures of both compounds and protonated analogs are found to prefer a chair-chair-conformation of the piperidine and cyclohexane rings with two mirror image orientations of the phenyl and methoxyl groups. Comparison of the protonated a- and B- azabicyclanes for the same conformation revealed very similar orientations of the pharmacophoric groups (phenyl, methoxyl and tertiary N) which suggest that interchange of piperidine and cyclohexane rings has minimal effect on the relative conformation of the pharcophoric groups. These may account for the observed similarity of their opiate activities. A detailed comparison is also made between the optimized models and those obtained by X-ray crystallography with satisfactory agreement in geometries despite the different molecular environments of the two methods calculations were done in the gas phase while X-ray data were obtained from the solid phase.