Synthesizing Opioid Antagonists: A more sustainable method for creating a lifesaving drug


With an increasing intensity in the nation’s opioid epidemic, the public health community has been searching for ways to manage drug addiction. Chemical antagonists have proven effective in binding to opioid receptors, thus competing with opioid agonists and blocking them from binding and activating opioid receptors. Researchers Sun Dongbang, Blaine Pedersen, and Jonathan Ellman have formulated a method to asymmetrically synthesize an opioid antagonist compound called naltrexone, without the use of thebaine as a starting material.

 Using naturally sourced thebaine requires poppy cultivation, because thebaine is derived from and comprises 2% of opium. Reliance on poppy farming is controversial because it often leads to illegal production and sale of opium on the black market, which perpetuates violent and illicit drug trafficking. These researchers set out to investigate a novel synthetic route that bypassed the need for thebaine. Dongbang, Pedersen, and Ellman devised an attainable, revolutionary mechanism, involving 17 steps, to forego any need for thebaine. The reaction includes the novel usage of Cu (II) and O2 for C-H allylic oxidation. The researchers were the first to use this step in synthesizing naltrexone. Naltrexone has important properties that make it vital as an anti-overdose and drug-addiction treatment. The synthesis of this key opioid antagonist has the potential for commercial usage. Dongbang, Pedersen, and Ellman’s preparation of naltrexone is different from traditional methods of synthesis and semi-synthesis of thebaine, and may facilitate the production of opioid derivatives in the future. These findings will pave the way for an easier route for producing anti-addiction treatments, without reliance on poppy farming.