Crystal structure, absolute configuration and stereochemistry of nupharidine hydrobromide

Abstract

An X-ray diffraction study of nupharidine hydrobromide has been carried out in order to obtain an unequivocal solution to the question of the N-oxide configuration. Nupharidine hydrobromide (C₁₅H₂₄BrNO₂) crystals are orthorhombic, space groupP2₁2₁2₁ withz = 4. The unit cell constants at 22 ± 3 ° area = 13·419(2),b = 13·668(4),c = 8·731(2) Å (CuKα₁, λ = 1·54051 Å). Three-dimensional intensity data, to the limit 2θ = 145 ° for CuKα₁, were measured on a GE XRD-490 automatic diffractometer equipped with Ni-Co balanced filters for monochromatization. The crystal structure was solved by the heavy-atom method and refined by least squares to anR of 0·06 for 1960 reflections.

X-ray analysis clearly established that (a) the quinolizidine N-oxide system is built of twocis-fused chairs, (b) the methyl and the furan substituents occupy the equatorial position and (c) the absolute configuration indicated by the chemical methods is in agreement with the X-ray work. The stereochemical aspects of the Polonovski elimination reaction in the conversion of (+) nupharidine to Δ⁶-dehydrodeoxynupharidine has been studied in the light of these X-ray results.