DOI: https://doi.org/10.24959/ophcj.13.765

A new method for synthesis of atomoxetine and its interaction with with azole-con¬taining sulfonyl chlorides

M. K. Korsakov, L. O. Shumilova, V. O. Postnov, M. V. Dorogov, M. Yu. Solovyov

Abstract


A new approach to the synthesis of atomoxetine using the methods of enzymatic catalysis has been developed;
the interaction of atomoxetine with a number of azole-containing heterocyclic sulfochlorides has been studied. The
carbonyl group of 3-chloro-1-phenyl-propane-1-one was region-specifically reduced with NADPH-dependent
carbonylreductase (SSCR) in phosphate buffer solution. In Mitsunoby reaction with o-methylphenole the inversion
of the final product configuration takes place and [R]-1-(3-chloro-1-phenypropoxy)-2-methylbenzene is formed.
Its further treatment with methylamine results in the base of atomoxetine, which may be isolated from the solution
as a chloride. In order to develop the novel biologically active compounds the series of sufonyl chlorides with
oxazole and isoxazole substituents were reacted with atomoxetine. The sulfonamides obtained fully comply with
all criteria for the molecules – candidates for the biomedical study.


Keywords


atomoxetine; enzymatic catalysis; carbonyl reductase; sulfonyl chloride; sulfonamide

References


Wee S., Woolverton W.L. // Drug and Alcohol Dependence. – 2004. – Vol. 75. – P. 271-276.

Chengfu X., Chengye Y. // Tetrahedron. – 2005. – Vol. 61, №8. – P. 2169-2186.

Castelli E., Lo Monaco G. // Пат. US2006/9489 A1. – 2006.

Ramanjaneyulu G., Ramdas C. // Пат. WO2008/26227 A2. – 2008.

Marvel C., Donald J.C. // J. Org. Chem. – 1959. – Vol. 24. – P. 957-962.


GOST Style Citations






Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)