Syntheses of Pentacyclic Morphinan Analogs

Abstract

The synthesis of a series of morphinans with an additional aromatic or alicyclic ring fused to the 5,6 positions or an alicyclic ring fused to the 16,17 positions is described. The synthetic sequence involved elaboration of a 1,2,3,4,5,6-hexahydrobenz[f]isoquinoline or a quinolizidine, Grewe cyclization to a morphinan, and modification of the functional groups of the morphinan. These morphinans showed poor to moderate analgesic and narcotic antagonist activity.