Synthesis of a new opioid ligand having the oxabicyclo[3.2.1]octane skeleton using a new rearrangement reaction

Akio Watanabe; Hideaki Fujii; Mayumi Nakajima; Ko Hasebe; Hidenori Mochizuki; Hiroshi Nagase

doi:10.1016/j.bmcl.2009.03.068

Synthesis of a new opioid ligand having the oxabicyclo[3.2.1]octane skeleton using a new rearrangement reaction

Bioorg Med Chem Lett. 2009 May 1;19(9):2416-9. doi: 10.1016/j.bmcl.2009.03.068. Epub 2009 Mar 21.

Authors

Akio Watanabe¹, Hideaki Fujii, Mayumi Nakajima, Ko Hasebe, Hidenori Mochizuki, Hiroshi Nagase

Affiliation

¹ School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.

PMID: 19349178
DOI: 10.1016/j.bmcl.2009.03.068

Abstract

An attempt to prepare a trimer having the 1,3,5-trioxazatriquinane skeleton led to discovery of a novel rearrangement reaction that afforded a compound with an oxabicyclo[3.2.1]octane skeleton whose reaction mechanism was proposed. On the basis of this mechanism, we synthesized the rearranged product from a dimethyl acetal intermediate in excellent yield. The compound with an oxabicyclo[3.2.1]octane skeleton showed high affinity for mu and kappa but not delta opioid receptor types. The compound expected to be a key intermediate for novel kappa selective ligands.

MeSH terms

Acetals / chemistry
Analgesics, Opioid / chemical synthesis*
Chemistry, Organic / methods
Chemistry, Pharmaceutical / methods*
Drug Design
Kinetics
Ligands
Models, Chemical
Molecular Conformation
Morphinans / chemistry
Morphine / chemistry
Receptors, Opioid, delta / chemistry
Receptors, Opioid, kappa / agonists*
Receptors, Opioid, kappa / chemistry
Receptors, Opioid, mu / chemistry
Spiro Compounds / chemistry

Substances

Acetals
Analgesics, Opioid
Ligands
Morphinans
Receptors, Opioid, delta
Receptors, Opioid, kappa
Receptors, Opioid, mu
Spiro Compounds
TRK 820
Morphine