Biotransformation of terodiline. v. stereoselectivity in hydroxylation by human liver microsomes

Abstract The stereoselective hydroxylation of N - tert -butyl-4,4-diphenyl-2-butylamine (Terodiline) was studied in human liver microsomes. Formation of the two main metabolites, N - tert -butyl-4(4-hydroxyphenyl)-4-phenyl-2-butylamine (II) and N -(2-hydroxymethyl-2-propyl)-4,4-diphenyl-2-butylamine (VI), was found to be stereoselective. R -Terodiline was preferentially transformed by phenolic hydroxylation to the 2 R ,4 S - II and 2 R ,4 R - II forms with a pronounced selectivity for the former. The formation rate ratio 2 R ,4 S - II /2 R ,4 R - II was about 6, obtained from two liver preparations. S -Terodiline was mainly hydroxylated to the alcohol 2 S - VI although phenolic hydroxylation to the 2 S ,4 S - II and 2 S ,4 R - II also occured, yielding about equal amounts of the two phenols.