| Research Abstract |
Considering that both cerebrovascular agents and muscarinic agonists for the treatment for Alzheimer's disease have the substituted piperidine as a common key structural feature, we have investigated the development of new synthetic strategy for both medicinals employing the bicyclic heterocycles, alkylthiofuropyridone, as a synthon.
We first established an efficient synthetic route for a valuable synthon, alkylthiofuropyridone' via the route involving the reductive photocyclization of the alkylthio-enamides. Potentiality of the furopyridone has been evaluated by the synthetically useful reactions involving three functional groups, alkylthio, enolether, and lactam carbonyl groups which have provided a novel carbon-carbon bond formation and ring transformation reactions.
Reductive photocyclization of alkylthio-enamides, prepared from the carboxylic acid, primary amine, and furoyl chloride, in the presence of sodium borohydride proceeded smoothly to give two types of alkylthiofuropyridones. Alkylation of the furopyridone via the lactam carbonyl-enolate gave the 3, 4-disubstituted piperidines which were efficiently converted into the analogues of the known muscarinic agonists and also into the biologically active alkaloids, tecomanine (hypoglycemic activity), quinine (antimalarial agent), emetine (antiamebic agent), and ajmalicine (adrenergic blocking agent). Elimination-addition reaction of another furopyridone gave the 3, 3-disubstituted piperidines, some of which have proved common intermediates for the synthesis of eburnamine-vincamine alkaloids, eburnamonine (cerebrovascular agent) and cuanzine (antiarrhythmic, vasodilatory, and antihypertensive activties).
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