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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Bibliographic Details
Published in:International journal of molecular sciences 2023-07, Vol.24 (14), p.11794
Main Authors: Pospelov, Evgeny V, Sukhorukov, Alexey Yu
Format: Article
Language:English
Subjects:
Amines
Amino acids
Drug approval
Gases industry
heterogeneous catalytic hydrogenation
Hydrogenation
Michael addition
Nitrogen
oximes
Pharmaceuticals
Piperazine
piperazines
reductive cyclization
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241411794