• Guru Row T N

      Articles written in Journal of Chemical Sciences

    • A new synthesis of Entacapone and report on related studies

      Attimogae Shivamurthy Harisha Suresh Parameshwar Nayak Pavan M S Shridhara K Sundarraja Rao K Rajendra K Koteppa Pari Sivaramkrishnan H Guru Row T N Kuppuswamy Nagarajan

      More Details Abstract Fulltext PDF

      A 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 NO2 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 $_{}^{13}$C spectra. Preliminary studies reveal in vitro activity for some compounds against tuberculosis (TB) and dengue.

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