Abstract
β-Amino-α-ketoamides 1 are a class of compounds exhibiting biological activity as reversible covalent enzyme inhibitors. The representative examples are clinically approved drugs for the treatment of hepatitis C virus Boceprevir 2 and Telaprevir 3. β-Amino-α- ketoamide substructure is also found in a number of natural products, many of which display a remarkable biological activity. The methods for the synthesis of β-amino-α-ketoamide can be classified based on the key steps of the synthetic routes: from unsaturated amide involving epoxydation followed by a regioselective azidolysis; from esters involving aminohydroxylation; from adehydes via Passerini reaction, cyanohydrin formation, addition of the masked acylcyanide (MAC) reagent or orthothioester; from imines via addition of dithiolane derived from oxoacetic acid, addition of isoxazolyl-4-triflates or via azetidinone formation; from acids via acylation of (cyanomethylene) triphenylphosphorane (the Wasserman procedure), via acylfurane formation or via Dakin-West reaction; from nitroalkanes via Henry reaction. In this review, the information from the scientific literature published within the period from 1990 till 2014 for the synthesis of β-amino-α-ketoamides is covered and systematized according to the above mentioned key steps.
Keywords: Azetidinones, cyanohydrins, dakin-west reaction, epoxides, MAC reagent, orthothioesters, henry reaction, passerini reaction, protease inhibitors, wasserman procedure, β-Amino-α-ketoamides.
Current Organic Chemistry
Title:Synthesis of β-amino-α-ketoamides
Volume: 18 Issue: 17
Author(s): Samir Kher and Aigars Jirgensons
Affiliation:
Keywords: Azetidinones, cyanohydrins, dakin-west reaction, epoxides, MAC reagent, orthothioesters, henry reaction, passerini reaction, protease inhibitors, wasserman procedure, β-Amino-α-ketoamides.
Abstract: β-Amino-α-ketoamides 1 are a class of compounds exhibiting biological activity as reversible covalent enzyme inhibitors. The representative examples are clinically approved drugs for the treatment of hepatitis C virus Boceprevir 2 and Telaprevir 3. β-Amino-α- ketoamide substructure is also found in a number of natural products, many of which display a remarkable biological activity. The methods for the synthesis of β-amino-α-ketoamide can be classified based on the key steps of the synthetic routes: from unsaturated amide involving epoxydation followed by a regioselective azidolysis; from esters involving aminohydroxylation; from adehydes via Passerini reaction, cyanohydrin formation, addition of the masked acylcyanide (MAC) reagent or orthothioester; from imines via addition of dithiolane derived from oxoacetic acid, addition of isoxazolyl-4-triflates or via azetidinone formation; from acids via acylation of (cyanomethylene) triphenylphosphorane (the Wasserman procedure), via acylfurane formation or via Dakin-West reaction; from nitroalkanes via Henry reaction. In this review, the information from the scientific literature published within the period from 1990 till 2014 for the synthesis of β-amino-α-ketoamides is covered and systematized according to the above mentioned key steps.
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Cite this article as:
Kher Samir and Jirgensons Aigars, Synthesis of β-amino-α-ketoamides, Current Organic Chemistry 2014; 18 (17) . https://dx.doi.org/10.2174/1385272819666140818223225
DOI https://dx.doi.org/10.2174/1385272819666140818223225 |
Print ISSN 1385-2728 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5348 |
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