Eseroline

 ( Semisynthetic Opioids ) 

Eseroline is a drug which acts as an opioid agonist. It is a metabolite of the acetylcholinesterase inhibitor physostigmine but unlike physostigmine, the acetylcholinesterase inhibition produced by eseroline is weak and easily reversible, and it produces fairly potent analgesic effects mediated through the μ-opioid receptor. This mixture of activities gives eseroline an unusual pharmacological profile, although its uses are limited by side effects such as respiratory depression and neurotoxicity.

---

Synthesis The alkylation of phenacetin ( 1) with dimethyl sulfate gives N-methylphenetidine ( 2). Treatment with 2-bromopropanoyl bromide gives 2-bromo- N-(4-ethoxyphenyl)- N-methylpropanamide ( 3). Treatment with aluminium trichloride results in 1,3-dimethyl-5-hydroxyoxindole ( 4). Alkylation with diethyl sulfate gives 5-ethoxy-1,3-dimethylindolin-2-one ( 5). Base-catalyzed treatment with chloroacetonitrile gives 2-(5-ethoxy-1,3-dimethyl-2-oxoindol-3-yl)acetonitrile ( 6). Catalytic hydrogenation of the nitrile group gives ( 7). Mono-methylation of the primary amine gives ( 8). Intramolecular reductive amination gives eserethole ( 9). Cleavage of the ethyl ether protecting group gave (-)-eseroline ( 10). Optional treatment with methyl isocyanide (MIC) leads to physostigmine.

Post Comment