October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
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) |
NIDA |
CHEMCELL-1 |
Authors
- J. F. Antoline
- J. L. Deck
- K. C. Rice
- A. E. Jacobson
Abstract
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.
