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Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes

Piperazine is one of the most frequently found scaffolds in small-molecule FDA-approved drugs. In this study, a general approach to the synthesis of piperazines bearing substituents at carbon and nitrogen atoms utilizing primary amines and nitrosoalkenes as synthons was developed. The method relies...

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Autores principales: Pospelov, Evgeny V., Sukhorukov, Alexey Yu.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380651/
https://www.ncbi.nlm.nih.gov/pubmed/37511552
http://dx.doi.org/10.3390/ijms241411794
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author Pospelov, Evgeny V.
Sukhorukov, Alexey Yu.
author_facet Pospelov, Evgeny V.
Sukhorukov, Alexey Yu.
author_sort Pospelov, Evgeny V.
collection PubMed
description Piperazine is one of the most frequently found scaffolds in small-molecule FDA-approved drugs. In this study, a general approach to the synthesis of piperazines bearing substituents at carbon and nitrogen atoms utilizing primary amines and nitrosoalkenes as synthons was developed. The method relies on sequential double Michael addition of nitrosoalkenes to amines to give bis(oximinoalkyl)amines, followed by stereoselective catalytic reductive cyclization of the oxime groups. The method that we developed allows a straightforward structural modification of bioactive molecules (e.g., α-amino acids) by the conversion of a primary amino group into a piperazine ring.
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spelling pubmed-103806512023-07-29 Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes Pospelov, Evgeny V. Sukhorukov, Alexey Yu. Int J Mol Sci Article Piperazine is one of the most frequently found scaffolds in small-molecule FDA-approved drugs. In this study, a general approach to the synthesis of piperazines bearing substituents at carbon and nitrogen atoms utilizing primary amines and nitrosoalkenes as synthons was developed. The method relies on sequential double Michael addition of nitrosoalkenes to amines to give bis(oximinoalkyl)amines, followed by stereoselective catalytic reductive cyclization of the oxime groups. The method that we developed allows a straightforward structural modification of bioactive molecules (e.g., α-amino acids) by the conversion of a primary amino group into a piperazine ring. MDPI 2023-07-22 /pmc/articles/PMC10380651/ /pubmed/37511552 http://dx.doi.org/10.3390/ijms241411794 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pospelov, Evgeny V.
Sukhorukov, Alexey Yu.
Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes
title Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes
title_full Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes
title_fullStr Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes
title_full_unstemmed Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes
title_short Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes
title_sort building up a piperazine ring from a primary amino group via catalytic reductive cyclization of dioximes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380651/
https://www.ncbi.nlm.nih.gov/pubmed/37511552
http://dx.doi.org/10.3390/ijms241411794
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