Amide-bond condensation

The leader of DuPont s effort was Wallace H Carothers who reasoned that he could reproduce the properties of silk by constructing a polymer chain held together as is silk by amide bonds The neces sary amide bonds were formed by heating a dicar boxylic acid with a diamine Hexanedioic acid adipic acid) and 1 6 hexanediamme hexamethylenedi-amine) react to give a salt that when heated gives a polyamide called nylon 66 The amide bonds form by a condensation reaction and nylon 66 is an example of a condensation polymer... 

FIGURE 27 13 The mechanism of amide bond formation by W W dicyclohexylcarbodiimide promoted condensation of a carboxylic acid and an amine... 

The a-ionization of 7-methylpteridines can also be utilized in aldol-type condensation reactions. 7-Methyl-pterin and -lumazine and 2,4-diaminopteridine condense readily in aqueous base with aromatic aldehydes to afford 7-alkylidenepteridines (77JOC2951). A Claisen condensation requires the protection of the acidic hydrogens of the amide bonds. 

Application of the Knorr pyrazole synthesis has also been demonstrated on solid support. ° To prepare trisubstituted pyrazoles, the diketone was linked to the solid support to make 57 using a linker with an amide bond. Alkylation of the diketone followed by condensation of the hydrazine with the resulting diketone gave the desired pyrazoles as mixtures of isomers. Subsequent cleavage of the amide bond linker then provided the pyrazole amides 59. ... 

Saturation of the aromatic ring of pentopril analogues is also consistent with ACE inhibition as demonstrated by the oral activity of indolapril (23). The necessary heterocyclic component (21) can in principle be prepared by catalytic perhydrogenation (Rh/C, HOAc) of the corresponding indole. A single isomer predominates. The product is condensed by amide bond formation with the appropriate alanylhomophenylalanyl dipeptide ester 20 to give 22. Selective saponification to 23 could be accomplished by treatment with HCl gas. Use of the appropriate stereoisomers (prepared by resolution processes) produces chiral indolapril [8]. 

KEY TERMS amide bond or amide linkage hydrogen bond aramid condensation polymer or condensation reaction... 

The first experiments on chemoautotrophic theory were carried out by Stetter at the University of Regensburg. It was found that synergy in the FeS/H2S system determined the reductive effect, for example, in the conversion of nitrate to ammonia or of alkynes to alkenes. The conditions used corresponded to those present in hydrothermal systems aqueous phase, 373 K, almost neutral pH and anaerobic conditions (Blochl et al 1992). Two years later, the formation of an amide bond without the use of a condensation agent was successfully demonstrated in the same laboratory (Keller et al 1994). 

Successive amino acids are joined together during protein synthesis via a peptide (i.e. amide) bond (Figure 2.2). This is a condensation reaction, as a water molecule is eliminated during bond formation. Each amino acid in the resultant polypeptide is termed a residue , and the polypeptide chain will display a free amino (NH2) group at one end and a free carboxyl (COOH) group at the other end. These are termed the amino and carboxyl termini respectively. 

When considered in isolation, peptide bonds are in many ways analogous to standard amide bonds. They are kinetically stable, in the sense that hydrolysis under physiological conditions of temperature and pH is very slow, with ty2 values that can be counted in years. However, they are thermodynamically unstable in the sense that the equilibrium constant favors hydrolysis over condensation by a factor of 103 to 104. 

In a hydrolysis reaction, water adds to a bond, splitting it in two. This reaction is the reverse of a condensation reaction. For example, water can add to an ester or amide bond. A carboxylic acid and an alcohol are produced if an ester bond is hydrolyzed, as shown in the example below. A carboxylic acid and an amine are produced if an amide bond is hydrolyzed. 

Condensation polymerization is a reaction in which monomers are joined together by the formation of ester or amide bonds. A second smaller product, usually water, is produced by this reaction. For condensation polymerization to occur, each monomer must have two functional groups (usually one at each end of the molecule). 

Nylon-66 is made by the condensation polymerization of the dicarboxylic acid adipic acid, and 1,6-diaminohexane, an amine. (The number 66 comes from the fact that each of the two reactants contains six carbon atoms.) This reaction results in the formation of amide bonds between monomers, as shown in Figure 2.13. Condensation polymers that contain amide bonds are called nylons or polyamides. Condensation polymers that contain ester bonds are called polyesters. Polyesters result from the esterification of diacids and dialcohols. 

C domains that oatalyzed the formation of multiple amide bonds Transglutaminases Chain Termination Strategies Thioesterase-catalyzed chain release Alternative chain release through reduction Condensation domains as chain termination catalysts Diketopiperazine formation Oxidative ohain termination... 

C domains can display functions that deviate from typical amide bond formation. Several C domains are postulated to act as ester synthases, catalyzing ester formation instead of amide formation. NRPS modules containing C domains that display this activity are present in the biosynthetic pathways for the kutznerides, cryptophycins, " cereulide, valinomycin, hectochlorin, and beauvericin. Each of these C domains likely utilizes a PCP-bound a-hydroxyl acceptor in the condensation reaction. Another NRPS C domain that catalyzes ester bond formation is involved in the biosynthesis of the polyketide-derived mycotoxins known as the fiimonisins. Du and coworkers have shown that a recombinant PCP-C didomain of an NRPS involved in the biosynthetic pathway of the fnmonisins can catalyze ester bond formation between hydroxyfumonisins and the A-acetylcysteamine thioester of tricarballylic acid, even though PCP-bound tricarballylic acid is not... 

Another set of unusual C domains include those that catalyze the formation of more than one amide bond on an acceptor substrate containing multiple amine moieties. For example, the C domain of the NRPS module FscI in fuscachelin biosynthesis likely catalyzes amide bond formation at both the a- and -amines of a PCP-bound L-hOrn intermediate. Other domains displaying similar activity include the condensation domain of MxcG, the third C domain of CchH, and the second C domain of VibF from the biosynthetic pathways for myxochelin, coelichelin, and vibriobactin, respectively. 

Historically, the methods used for ring closure of linear precursor peptides via amide bond formation evolved in parallel to the methods applied in segment condensations from the azide and active ester procedures to the use of coupling reagents such as DCC in the presence of additives, or of the more recently developed phosphonium and uronium/gua-nidinium reagents. In all cases the choice of method is mainly dictated by the epimerization problem when chiral amino acids act as the carboxy component in the cyclization reaction, and by other side reactions. 

In biosynthesis the heterocyclic units are generated from dipeptide precursors via a multienzyme complex mediated condensation of the p-thiol group of a cysteine residue with the carbonyl group of the preceding amide bond without or with subsequent dehydration, thus leading to the amino- and carboxy-functionalized thiazolyl and dihydrothiazolyl derivatives shown in Scheme 34, 538 ... 

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