The synthesis of glucuronides derived from the antidepressant drugs mianserin and Org 3770

Abstract

Abstract The synthesis of glucuronides derived from mianserin and its 6‐aza analogue (Org 3770) is described. Several methods were investigated. The most successful approach was the coupling of 1,2,3,4,10,14b‐hexahydro‐8‐hydroxy‐2‐(trifluoroacetyl)dibenzo[ c,f ]pyrazino[1,2‐ a ]azepine or its 6‐aza analogue with methyl [trichloroethanimidoyl 2,3,4‐tris‐ O ‐(phenylmethyl)‐α‐D‐glucopyranosid]uronate catalyzed by BF 3 . Fully protected glycosides were obtained as diastereomeric β/α mixtures. After deprotection the glucuronides of 2‐demethylmianserin and 2‐demethyl‐Org 3770 were synthesized. The corresponding N (2)‐methyl analogues were obtained by reductive methylation. The synthetic β‐glucuronides were identical with the isolated metabolites of mianserin and Org 3770.