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Synthesis and Structural Elucidation of a Pyranomorphinan Opioid and in Vitro Studies
Mohd Imran Ansari1, Jason R Healy2, Kellie Hom1
1Department of Pharmaceutical Sciences , University of Maryland School of Pharmacy , 20 North Pine Street , Baltimore , Maryland 21201 , United States.
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.
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