Catalytic aerobic oxidation of nor-binaltorphimine (nor-BNI) analogs without 4,5-epoxy bridge affords a more selective ligand for kappa opioid receptor than the representative kappa antagonist nor-BNI

Abstract

An analog of nor-binaltorphimine (nor-BNI) without the 4,5-epoxy bridge, 17,17'-bis(cyclopropylmethyl)-6,6',7,7'-tetrahydro-6,6'-imino-14beta,14'alpha-dihydroxy-3,3'-dimethoxy-7,7'-bimorphinan (4), which was the precursor of the designed compound 1 as a selective kappa(3) opioid receptor antagonist, was catalytically oxidized with oxygen in the presence of platinum to give the 5'-oxo derivative 3 with some other oxidized products. Morphinan derivatives without the 4,5-epoxy moiety were labile to oxygen, although the corresponding 4,5-epoxymorphinan derivatives resisted aerobic oxidation. One of the oxidized nor-BNI analogs without 4,5-epoxy bridge, compound 18, showed high affinity and selectivity for kappa opioid receptor.