Evolution of amide bond formation

Abstract

This paper is dedicated to Drs Bruce E. Maryanoff and Cynthia A. Maryanoff for their outstanding contribution to organic chemistry as industrial chemists AbstractThe presence of carboxamide groups is found in a large array of biologically important compounds. Peptides and proteins play an important role in modern biology. A key step in peptide production is the formation of the peptide bond, which involves amide bond formation. Chemical synthesis of large peptides by intermolecular coupling of smaller peptides using conventional peptide bond-forming techniques did not realize its potential advantages until recently. Using an approach based on highly specific and efficient chemical ligation of two peptide segments, the two subunits were ligated to form a new peptide bond. Native chemical ligation extended the concept by creating a native peptide bond and providing new approaches to protein engineering.

The enhancement of direct amide synthesis reaction rate over TiO 2 @SiO 2 @NiFe 2 O 4 magnetic catalysts in the continuous flow under radiofrequency heating

“…About 25 % of all drugs on the market contain amide bonds, and the amide synthesis covers 65 % of drug candidates [24]. Detailed methodologies for the amide formation are presented in several recent reviews [24][25][26][27]. In summary, the traditional synthesis involves the activation of carboxylic acids followed by ammonolysis of the activated compound to obtain amide as presented in Fig.…”

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

“…Encouraged by our results, we started the library production planning to use the 3-step process requiring 2 purification steps by preparative LC–MS. However, as we planned to introduce a significant amount of steric and electronic diversity from the C-3 amide vector, we switched the amide coupling agent from TBTU to the more reactive HATU [ 8 – 9 ]. To our surprise, the amide coupling step furnished almost quantitatively the C2–OAt ether 15 [ 10 ] and only traces of the expected C2–Cl amide product 14 .…”

Efficient, Solvent-Free Aminolysis of Monoesters Catalyzed by Sodium

“…[5] Ester aminolysis is the classical method for making amides, regardless of the lower level activation of esters than acyl halides, anhydrides acyl azides and acylimidazoles, as esters produce fewer side reactions. [6] For example, acyl chlorides [7] were prone to be hydrolyzed in the reaction with ammonia, the same holds true for the reaction of trifluoroacetic anhydride [8] with ammonia in methanol. Carboxylic acid ammoniolysis is also a common method for making amides.…”