Enzymatic resolution of analgesics: δ-hydroxytramadol, ε-hydroxytramadol and O-desmethyltramadol

Efficient enzymatic resolutions of the analgesic δ-hydroxytramadol rac - 3 and e-hydroxytramadol rac - 4 have been achieved through pig liver esterase- and Candida rugosa lipase-catalyzed hydrolyses of the corresponding butyrates. The Candida rugosa lipase-catalyzed hydrolysis of O -desmethyltramadol butyrate rac - 8a , having a remote aromatic acyloxy group as the only functional group amendable to a hydrolase-catalyzed reaction, proceeded with a good selectivity.