Synthesis of Novel 6β,14-Epoxy-Bridged Opiates

During the course of our research directed toward the development of selective opioid receptor antagonists, we discovered a novel opiate cyclization that makes the opiate C-ring rigid in a manner similar to the oripavines l.1 These new compounds (2a, 2b) have a 6,14/3-epoxy linkage in place of the 6,14/3-ethano bridge of Bently's1 extremely potent thebaine-derived oripavines 1. This was accomplished by an intramolecular ether-forming reaction of the relatively flexible C ring of 6a-(mesyloxy) opiates 4a and 4b, converting them into the rigid 1,4-epoxycyclohexane derivatives 2a and 2b.