Title:Synthesis of β-amino-α-ketoamides
VOLUME: 18 ISSUE: 17
Author(s):Samir Kher and Aigars Jirgensons
Affiliation:Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia.
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.
