eseroline

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.