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Scalable synthesis of C-9 functionalized phenylmorphans as probes for narcotic receptor mediated phenomena

Thursday, November 07, 2013 — Poster Session II

12:00 p.m. – 2:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • J. F. Antoline
  • J. L. Deck
  • K. C. Rice
  • A. E. Jacobson


As part of the ongoing effort to separate the analgesic properties of opioids from their detrimental side effects, we have identified several 9-functionalized 5-phenylmorphans as potent and selective mu opioid receptor agonists. Based on quantum mechanical calculations, variation of the C-9 functionality could lead to a highly prized mu agonist/delta antagonist compound. To further probe the SAR around C-9, a scalable, high yielding, chromatography free preparation of the key common intermediate en route to the 9-functionalized 5-phenylmorphans has been developed. The key step is an optimized thermal dequaternization protocol, which has been successfully performed on a 100g scale in greater than 80% yield. Further elaboration afforded the desired 1- and 2-carbon tethered C-9 alcohols. Current efforts are directed at developing a N-demethylation/alkylation protocol that tolerates the hydroxyl functionality in the molecule.

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