Novel synthesis of the ortho ester derivative of 4,5-epoxymorphinan.
[reaction: see text]. A method was found for the novel synthesis of ortho ester derivatives that are potentially useful as selective epsilon opioid receptor ligands. An unexpected 17-(cyclopropylmethyl)-4,5alpha-epoxy-6alpha-hydroxy-3,7,7-trimethoxy-8-oxa-6,14-endoethanomorphinan was produced when 17-(cyclopropylmethyl)-4,5alpha-epoxy-3-methoxy-6alpha,14-dihydroxy-6beta-(1,3-dithia-2-yl)-morphinan was treated in methanol with trimethyl orthoformate and CuO/CuCl2. This ortho ester derivative was then converted to an ester with acid. The structure of the ortho ester was determined by 2D NMR (HMBC) and mass spectra.
Watanabe
Akio
A
School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Kai
Toshitsugu
T
Nagase
Hiroshi
H
D004952:Esters; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C496139:4,5-epoxymorphinan; D004952:Esters; D009019:Morphinans