Amino acid stepwise condensation

The resulting amino acid then condenses in a stepwise manner to form the growing polymer chain. As in direct polymerization, cycHc oligomers are also formed hence, caprolactam (qv) can be formed in the reverse of the reaction just shown above. 

An old but practical synthetic method for 2(l//)-pyrazinones is Jones procedure which involves condensation of a-amino amides with 1,2-dicarbonyl compounds (Section 8.03.9.1). A number of stepwise approaches using a-amino acids to 2(177)-pyrazinones have been discussed in Section 8.03.9.4. 

Elongation of the peptide bearing a reduced bond can be performed stepwise or by fragment condensation. In the latter case, the carbonyl of the amino acid involved in the reduced peptide bond can be activated (Scheme 1) as no racemization by the oxazol-5(4//)-one mechanism can occur. 

Nylon-6, a condensation polymer, can be produced by chainwise, ring openings of cyclic amide (lactam) without expulsion of small molecules, and also by stepwise polycondensation of < -amino acid. 

In the case of the stepwise synthesis of peptide fragments starting from an amino acid without C-terminal protection, peptide bond forming methods are limited to the mixed anhydride method,the active ester method, and the azide methodJ l Although such peptide fragments can be directly used for the segment condensation reaction, the purification of the products after each coupling reaction is not so easy. 

All the methods of peptide bond formation described in Section 3 are useful for the synthesis of peptides on solid support [solid-phase peptide synthesis (SPPS)]. The ideal method would rapidly allow quantitative coupling reactions under mild conditions, avoiding side reactions, racemization, and generating side-products which could be easily removed by single washings from the peptide-resin. Various techniques have been explored by peptide chemists, but the focus of this section will be on the small number which have been widely used. These techniques have been applied to stepwise synthesis , the addition of one residue at a time, and to fragment condensation , which is the condensation of long sequences of amino acids. 

As we have seen in these chapters on acylation methods in stepwise and segment condensation peptide synthesis, considerable progress towards efficient procedures to couple amino acids and peptides by an amide bond have been made, particularly in the areas of coupling agents, enzyme-catalyzed coupling, and ligation methods. Problems still arise when... 

BPS catalyzed the stepwise condensation of benzoyl-CoA with three molecules of malonyl-CoA to give a tetraketide intermediate that was cyclized by intramolecular Claisen condensation into 2,4,6-trihydroxybenzophenone (Figure 2). The enzyme was inactive with CoA-linked ciimamic acids such as 4-coumaroyl-CoA, the preferred starter substrate for chalcone synthase (CHS). BPS and CHS from H. androsaemum cell cultures shared 60.1% amino acid sequence identity. CHS is ubiquitous in higher plants and the prototype enzyme of the type III PKS superfamily (1,2). It uses the same reaction mechanism like BPS to form 2, 4,4, 6 -tetrahydroxychalcone, the precursor of flavonoids (Figure 2). 

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