A. Harisha, S. Nayak, P. S
Dec 5, 2015
Citations
0
Influential Citations
7
Citations
Journal
Journal of Chemical Sciences
Abstract
AbstractA new synthesis of the catechol-O-methyltransferase (COMT) inhibitor, entacapone (E-isomer) has been achieved under mild conditions by amine-mediated demethylation of the precursor 2-Cyano-3-(3- hydroxy-4-methoxy-5-nitrophenyl) prop-2-eneamide, wherein the methoxyl group adjacent to a nitro group gets demethylated under nucleophilic attack. Similar demethylation was achieved on ethyl 2-cyano-3-(3, 4-dimethoxy-5-nitrophenyl) prop-2-enoate, 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethylprop-2-enamide, ethyl 2-cyano-3-(3-hydroxy-4-methoxy-5-nitrophenyl) prop-2-enoate and ethyl 2-cyano-3-(4-methoxy-3-nitrophenyl) prop-2-enoate. The scope of demethylation has been studied. Analogues of ethyl 2-cyano-3-(3, 4-dimethoxy-5-nitrophenyl) prop-2-enoate wherein a methoxyl group is not adjacent to a NO 2 group are unaffected and phenolic derivatives yield the amine salts. Entacapone has been converted to salts with organic bases. The crystal structure of the isomer of entacapone (Z-isomer), a significant human metabolite of E-isomer has been established. NMR methods for deriving E and Z geometry and other similar molecules have been successfully established, mainly by studying the proton coupled 13C spectra. Preliminary studies reveal in vitro activity for some compounds against tuberculosis (TB) and dengue. Graphical AbstractA new synthesis of entacapone 1 of a designed precursor under very mild conditions is reported. Crystal structure of its Z isomer, NMR methods for establishment of E and Z geometry of benzylidene derivatives are also reported.