The influence of stereochemistry on pKa, rate of quaternization and partition coefficients of corynantheidine-type alkaloids

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Abstract
In alkaloids of the corynantheidine group, the rate of quaternization at N-4 and the pKa values give a measure of the degree of steric hindrance at this site due to the axial hydrogen at C-3 and the ethyl group at C-20. These hinder the availability of the lone pair of electrons on N-4 to electrophiles. Partition coefficients indicate that lipid solubility is associated with planarity of the molecules; this explains why the more planar isomers (allo and normal) are more highly metabolized in microsomes than the less planar isomers (pseudo and epiallo).