N-Dealkylation of oxprenolol: Formation of 3-aryloxypropane-1,2-diol,3-aryloxylactic acid, and 2-aryloxyacetic acid metabolites in the rat

Article abstract of DOI:10.1002/jps.2600740109

Oxprenolol (1), like related β-adrenergic antagonists, undergoes oxidative N-dealkylation to form the corresponding 3-aryloxypropane-1,2-diol (2), 3-aryloxylactic acid (3), and 2-aryloxyacetic acid (4) metabolites. Compounds 3 and 4 were synthesized by conversion of 2-allyloxyphenol (5) to the aryloxyacetaldehyde 6 and subsequent elaboration to the desired acids. Both acids (3 and 4) and glycol 2 were confirmed as metabolites formed from 1 in vivo in the rat and in vitro in the rat liver 9000 x g supernatant fraction. Incubation of a pseudoracemate of 1, made up of equal molar amounts of (2S)-1-d₀ and (2R)-1-d₂, showed that 2 and 3 arise principally from (2S)-1 by S/R ratios of ~ 5:1 and 2:1, respectively. On the other hand, acetic acid derivative 4 arises about equally from both enantiomers of 1.