Synthesis of a new opioid ligand having the oxabicyclo[3.2.1]octane skeleton using a new rearrangement reaction.
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.
School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Akio
A
Watanabe
Hideaki
H
Fujii
Mayumi
M
Nakajima
Ko
K
Hasebe
Hidenori
H
Mochizuki
Hiroshi
H
Nagase
D000080:Acetals / Q000737:chemistry; D000701:Analgesics, Opioid / Q000138:chemical synthesis*; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D009019:Morphinans / Q000737:chemistry; D009020:Morphine / Q000737:chemistry; D017465:Receptors, Opioid, delta / Q000737:chemistry; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000737:chemistry; D017450:Receptors, Opioid, mu / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry
D000080:Acetals; D000701:Analgesics, Opioid; D008024:Ligands; D009019:Morphinans; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013141:Spiro Compounds; C111212:TRK 820; D009020:Morphine