Synthesis and Structural Elucidation of a Pyranomorphinan Opioid and in Vitro Studies

Org Lett. 2018 May 18;20(10):2984-2987. doi: 10.1021/acs.orglett.8b01025. Epub 2018 May 8.

Abstract

During optimization of the synthesis of the mixed μ opioid agonist/δ opioid antagonist 5-(hydroxymethyl)oxymorphone (UMB425) for scale-up, it was unexpectedly discovered that the 4,5-epoxy bridge underwent rearrangement on treatment with boron tribromide (BBr3) to yield a novel opioid with a little-studied pyranomorphinan skeleton. This finding opens the pyranomorphinans for further investigations of their pharmacological profiles and represents a novel drug class with the dual profile (μ vs δ) predicted to yield lower tolerance and dependence. The structure was assigned with the help of 1D, 2D NMR and the X-ray crystal structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analgesics, Opioid / chemistry*
  • Drug Tolerance
  • Molecular Structure
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu

Substances

  • Analgesics, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu