Catalytic Aerobic Oxidation of nor-Binaltorphimine (nor-BNI) Analogs without 4, 5-Epoxy Bridge Affords a More Selective Ligand for κ Opioid Receptor than the Representative κ Antagonist nor-BNI

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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-14β, 14'α-dihydroxy-3, 3'-dimethoxy-7, 7'-bimorphinan (4), which was the precursor of the designed compound 1 as a selective κ_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 κ opioid receptor.
2007-10-01