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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11794 |
| _version_ | 1797588995681550336 |
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| author | Evgeny V. Pospelov Alexey Yu. Sukhorukov |
| author_facet | Evgeny V. Pospelov Alexey Yu. Sukhorukov |
| author_sort | Evgeny V. Pospelov |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T01:00:00Z |
| format | Article |
| id | doaj.art-bab21c8599d04c7892b2a791584e48fe |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:00:00Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bab21c8599d04c7892b2a791584e48fe2023-11-18T19:45:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141179410.3390/ijms241411794Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of DioximesEvgeny V. Pospelov0Alexey Yu. Sukhorukov1N. D. Zelinsky Institute of Organic Chemistry, Leninsky Prospect, 47, Moscow 119991, RussiaN. D. Zelinsky Institute of Organic Chemistry, Leninsky Prospect, 47, Moscow 119991, RussiaPiperazine 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.https://www.mdpi.com/1422-0067/24/14/11794piperazinesreductive cyclizationMichael additionoximesheterogeneous catalytic hydrogenation |
| spellingShingle | Evgeny V. Pospelov Alexey Yu. Sukhorukov Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes International Journal of Molecular Sciences piperazines reductive cyclization Michael addition oximes heterogeneous catalytic hydrogenation |
| 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 | piperazines reductive cyclization Michael addition oximes heterogeneous catalytic hydrogenation |
| url | https://www.mdpi.com/1422-0067/24/14/11794 |
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