Synthesis of (−)-Oxycodone

Abstract

Our novel synthetic route to (-)-oxycodone, a semisynthetic opioid analgesic, features a palladium-catalyzed direct intramolecular arylation of an aryl bromide, oxidative dearomatization of a dihydrophenanthrenol, formation of a benzylic quaternary carbon by an intramolecular Michael addition of a malonate moiety, and construction of the morphinan skeleton via a Hofmann rearrangement/lactamization cascade.

Programmed serial stereochemical relay and its application in the synthesis of morphinans

“…To this end, phenolic ketone 18 was converted to its dioxolane derivative followed by a dioxolane-directed phenolic demethylation. 22 Dioxolane removal followed by treatment of the resulting phenolic ketone ( 19 ) with pyridinium tribromide 23 and subsequent heating smoothly delivered an inconsequential mixture of oxa-tetracycle 20 and arylbromide 20a . Next, relocation of the bridgehead olefin 24 in 20 / 20a first converged both compounds through hydrogenation and dioxolane formation, and on further exposure to NBS under radical conditions afforded styrene 21 .…”

Oxycodone self-administration in male and female rats

“…In 2014, over 10 million people reported non-medical use of prescription opioids, and there were approximately 19 thousand reported over-dose deaths (Compton et al 2016). Oxycodone is a semisynthetic opioid analgesic derived from thebaine, a minor constituent of opium (Kimishima et al 2014). Oxycodone is prescribed for acute and chronic pain and, at least in some countries, has replaced morphine as the most widely prescribed opioid painkiller (Soderberg Lofdal et al 2013).…”

Anodic Oxidation as an Enabling Tool for the Synthesis of Natural Products

“…Based on pioneering work by Miller, [98][99][100] an intramolecular aryl-aryl coupling also served as the key step for the construction of the characteristic morphinan skeleton in the total synthesis of (-)-oxycodone [101][102][103][104][105][106] published by Opatz, Schäfer and Waldvogel. 102 The trioxygenated laudanosine derivative 41 was electrolyzed under constant current conditions, furnishing morphinandienone 42 in 69% yield (Scheme 9).…”