Structural Studies of Norditerpenoid Alkaloids: Conformation Analysis in Crystal and in Solution States

European Journal of Organic Chemistry
2021.0

Abstract

Conformational analyses are presented of several pharmacologically important norditerpenoid alkaloids (NDAs), in crystal and in solution states. Crystal data of 8 NDAs (4 free bases and 4 salts) were obtained, in which crassicauline A, aconitine HCl, and methyllycaconitine HClO4 are reported for the first time. 1D/2D NMR spectroscopies of 7 NDAs (5 free bases and 2 salts) were recorded comprehensively. Crystal conformations of NDAs are described with a revised cyclohexane ring nomenclature. The A/E-rings of NDA-free bases exist in twisted-chair/twisted-chair conformations, leading to examples of the H-1 NMR effect of steric compression shown in the A-ring. The A/E-rings of NDA salts adopt boat/chair crystal conformations, as does the protonated synthetic [3.3.1]azabicycle in its crystal lattice. However, in aqueous solutions at physiological pH, this protonated analogue adopts a true chair/true chair conformation where the NDA salts retain their twisted boat/twisted chair conformations.

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