Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles

Abstract The first diastereoselective synthesis of spirothiooxindoles is reported via the Michael reaction between thiooxindoles and dibenzalacetones. The reaction was conducted without any catalyst or additive under green conditions, i.e., ethanol as the solvent and at room temperature. In addition...

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Autores principales:	Firouz Matloubi Moghaddam, Vahid Saberi, Ashkan Karimi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a3cfdec1d724ea493940741ea5e4f41
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spelling	oai:doaj.org-article:4a3cfdec1d724ea493940741ea5e4f412021-11-28T12:18:01ZHighly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles10.1038/s41598-021-01766-62045-2322https://doaj.org/article/4a3cfdec1d724ea493940741ea5e4f412021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01766-6https://doaj.org/toc/2045-2322Abstract The first diastereoselective synthesis of spirothiooxindoles is reported via the Michael reaction between thiooxindoles and dibenzalacetones. The reaction was conducted without any catalyst or additive under green conditions, i.e., ethanol as the solvent and at room temperature. In addition, the described robust method benefits from scalability, simple work-up, and column chromatography-free purification. This work demonstrates the art of governing regio- and stereoselectivity, which has been discussed in the light of Density Functional Theory calculations. Our method represents the first synthesis of spiro[cyclohexanone-thiooxindoles] with the relative configuration of the aryl moieties at the cyclohexanone ring as cis. The obtained cis-spirothiooxindoles, can be used to afford cis-spirooxindoles, which their synthesis had not been explored before. According to our molecular docking studies, cis-spirooxindoles demonstrate higher binding affinities than corresponding trans-spirooxindoles for the OPRT domain of the Leishmania donovani uridine 5′-monophosphate synthase (LdUMPS). Thus, the reported method may eventually be utilized to develop new hit compounds for leishmaniasis treatment.Firouz Matloubi MoghaddamVahid SaberiAshkan KarimiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Firouz Matloubi Moghaddam Vahid Saberi Ashkan Karimi Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles
description	Abstract The first diastereoselective synthesis of spirothiooxindoles is reported via the Michael reaction between thiooxindoles and dibenzalacetones. The reaction was conducted without any catalyst or additive under green conditions, i.e., ethanol as the solvent and at room temperature. In addition, the described robust method benefits from scalability, simple work-up, and column chromatography-free purification. This work demonstrates the art of governing regio- and stereoselectivity, which has been discussed in the light of Density Functional Theory calculations. Our method represents the first synthesis of spiro[cyclohexanone-thiooxindoles] with the relative configuration of the aryl moieties at the cyclohexanone ring as cis. The obtained cis-spirothiooxindoles, can be used to afford cis-spirooxindoles, which their synthesis had not been explored before. According to our molecular docking studies, cis-spirooxindoles demonstrate higher binding affinities than corresponding trans-spirooxindoles for the OPRT domain of the Leishmania donovani uridine 5′-monophosphate synthase (LdUMPS). Thus, the reported method may eventually be utilized to develop new hit compounds for leishmaniasis treatment.
format	article
author	Firouz Matloubi Moghaddam Vahid Saberi Ashkan Karimi
author_facet	Firouz Matloubi Moghaddam Vahid Saberi Ashkan Karimi
author_sort	Firouz Matloubi Moghaddam
title	Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles
title_short	Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles
title_full	Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles
title_fullStr	Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles
title_full_unstemmed	Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles
title_sort	highly diastereoselective cascade [5 + 1] double michael reaction, a route for the synthesis of spiro(thio)oxindoles
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4a3cfdec1d724ea493940741ea5e4f41
work_keys_str_mv	AT firouzmatloubimoghaddam highlydiastereoselectivecascade51doublemichaelreactionarouteforthesynthesisofspirothiooxindoles AT vahidsaberi highlydiastereoselectivecascade51doublemichaelreactionarouteforthesynthesisofspirothiooxindoles AT ashkankarimi highlydiastereoselectivecascade51doublemichaelreactionarouteforthesynthesisofspirothiooxindoles
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Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles

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