A new synthesis of Entacapone and report on related studies

Harisha, Attimogae Shivamurthy and Nayak, Suresh Parameshwar and Pavan, MS and Shridhara, K and Rao, Sundarraja K and Rajendra, K and Pari, Koteppa and Sivaramkrishnan, H and Row, Guru TN and Nagarajan, Kuppuswamy (2015) A new synthesis of Entacapone and report on related studies. In: JOURNAL OF CHEMICAL SCIENCES, 127 (11). pp. 1977-1991.

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Abstract

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 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 C-13 spectra. Preliminary studies reveal in vitro activity for some compounds against tuberculosis (TB) and dengue.

Item Type:	Journal Article
Publication:	JOURNAL OF CHEMICAL SCIENCES
Publisher:	INDIAN ACAD SCIENCES
Additional Information:	Copy right for this article belongs to the INDIAN ACAD SCIENCES, C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA
Keywords:	Mild demethylation; crystal structure; entacapone; Z-isomer; carbon; proton NMR; E, Z geometry
Department/Centre:	Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited:	14 Jan 2016 06:11
Last Modified:	14 Jan 2016 06:11
URI:	http://eprints.iisc.ac.in/id/eprint/53096

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