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Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β -functionalized α -ketoamides

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ABSTRACT

A sequential three-component process is described, starting from 3-arylmethylene-2,5-piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions. Their transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was also achieved in a single step.

No MeSH data available.


Synthesis of aziridines 2.
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C2: Synthesis of aziridines 2.

Mentions: The starting 3-arylmethylene-2,5-piperazinediones 1 were readily available by aldol condensation of 1,4-diacetyl-2,5-piperazinedione with aldehydes in the presence of potassium tert-butoxide, followed by deacetylation with hydrazine hydrate (see the Supporting Information File 1 for further details). As shown in Scheme 2, treatment of these materials with N-bromosuccinimide and methanol in dioxane followed by the addition of 1.2 equivalents of a primary or secondary amine or alcohol in the presence of 2 equivalents of sodium hydride afforded the highly substituted and functionalized aziridine derivatives 2. Under these conditions, it can be assumed that methoxide is the predominant base. The optimal reagent concentration was determined to be 0.2 M, since higher concentrations led to the precipitation of reaction intermediates and lower yields.


Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β -functionalized α -ketoamides
Synthesis of aziridines 2.
© Copyright Policy - Beilstein
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4979736&req=5

C2: Synthesis of aziridines 2.
Mentions: The starting 3-arylmethylene-2,5-piperazinediones 1 were readily available by aldol condensation of 1,4-diacetyl-2,5-piperazinedione with aldehydes in the presence of potassium tert-butoxide, followed by deacetylation with hydrazine hydrate (see the Supporting Information File 1 for further details). As shown in Scheme 2, treatment of these materials with N-bromosuccinimide and methanol in dioxane followed by the addition of 1.2 equivalents of a primary or secondary amine or alcohol in the presence of 2 equivalents of sodium hydride afforded the highly substituted and functionalized aziridine derivatives 2. Under these conditions, it can be assumed that methoxide is the predominant base. The optimal reagent concentration was determined to be 0.2 M, since higher concentrations led to the precipitation of reaction intermediates and lower yields.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

A sequential three-component process is described, starting from 3-arylmethylene-2,5-piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions. Their transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was also achieved in a single step.

No MeSH data available.