HYDROXYLATED METABOLITES OF LORATADINE - AN EXAMPLE OF CONFORMATIONAL DIASTEREOMERS DUE TO ATROPISOMERISM

The structures of two metabolites of the nonsedating antihistamine loratadine (1) were confirmed by synthesis. The metabolites 3a and 3b, which are hydroxylated in the bridgehead, were each prepared from tricyclic ketone 8 in seven steps. Each of these compounds was found to exist as a pair of conformational diastereomers which interconvert slowly at room temperature. These conformers arise due to the restricted conformational mobility inherent to the diaryl [a, d]cycloheptane ring system. © 1990, American Chemical Society. All rights reserved.