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

Yumiko Osa; Yoshihiro Ida; Hideaki Fujii; Toru Nemoto; Ko Hasebe; Shinobu Momen; Hidenori Mochizuki; Hiroshi Nagase

doi:10.1248/cpb.55.1489

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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

Yumiko Osa, Yoshihiro Ida, Hideaki Fujii, Toru Nemoto, Ko Hasebe, Shinobu Momen, Hidenori Mochizuki, Hiroshi Nagase

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Keywords: aerobic oxidation, morphinan, opioid, κ receptor, platinum catalyst

JOURNAL FREE ACCESS

2007 Volume 55 Issue 10 Pages 1489-1493

DOI https://doi.org/10.1248/cpb.55.1489

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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-14β,14′α-dihydroxy-3,3′-dimethoxy-7,7′-bimorphinan (4), which was the precursor of the designed compound 1 as a selective κ₃ 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.

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