Kinetically controlled synthesis

Lin, Y. and Finke, R.G., Novel polyoxoanion- and Bu4N+-Stabilized, Isolable, and Redissolvable, 20-30 nm Ir300 900 nanoclusters the kinetically controlled synthesis, characterization, and mechanism of formation of organic solvent-soluble, reproducible size, and reproducible catalytic activity metal... 

Figure 10.4 Time dependence and maximal yield in kinetically controlled synthesis of condensation products AN. (i) Product hydrolysis...

Kasche, V. (1986) Mechanism and yields in enzyme catalysed equilibrium and kinetically controlled synthesis of -lactam antibiotics, peptides and other condensation products. Enzyme Microb. Technol., 8, 4-16. 

In the kinetically controlled synthesis, an activated acyl donor (ester, amide, or anhydride) is used to form an acyl-enzyme intermediate. 

Compared to thermodynamically controlled synthesis, the initial rates of kinetically controlled synthesis are usually faster and the conversion can be complete. 

Kinetically controlled synthesis N-Xaa-esters Xaa-amides Corresponding peptides 90 14... 

The type of solvent can affect the kinetics, and, as a consequence, the equilibrium is sometimes not reached within a reasonable time. For example, Kim and Shin studied the kinetically controlled synthesis of alitame precursor (Z-Asp(OEt)-D-Ala-NH2), and better results were obtained in the presence of dimethyl sulfoxide and 2-methoxyethyl acetate as adjuvants. These solvents promoted product precipitation while maintaining the reaction mixture in a homogeneous state, thus improving the conversion [64]. 

Recently, the kinetically controlled synthesis of cephalexin with penicillin amidase was studied at very high concentrations of substrates to the limit of... 

There are two basic strategies for enzyme-catalyzed peptide synthesis equilibrium- and kinetically controlled synthesis. The former is the direct reversal of proteolysis and involves the condensation of an amino component with unactivated carboxyl component. The latter proceeds by the aminolysis of an activated peptide ester. 

Investigating the kinetically controlled synthesis of the /flactam antibiotic amoxicillin from 6-aminopenicillanic acid and D-p-hydroxyphenylglycine methyl ester in a solid suspension system in which the reaction nevertheless occurred in the liquid phase, Diender et al. found that the pH value and dissolved concentrations took a very different course at different initial substrate amounts (Diender, 2000). These results were described reasonably well by the model based on mass and charge balances, pH-dependent solubilities of the reactants, and enzyme kinetics. 

Fig. 7.2 Stoichiometric scheme of kinetically controlled synthesis of esters by transesterification from vinyl esters and alcohols catalysed by CALB...

Various parameters are known to influence the kinetically controlled synthesis of silica-rich zeolites and related compounds such as porosils. In syntheses where diethylenetriamine is acting as a structure-directing agent (SDA), different porosil structures can crystallize nonasil, ZSM-48, silicalite-1 and an unknown structure. The type of porosil obtained is found to depend upon the concentration of the SDA, i.e. upon the compositional ratio between diethylenetriamine and water in the synthesis gel. The results can be rationalized on the basis of the structural arrangements of the diethylenetriamine molecules in the porosil formed. These arrangements are influenced by the competition between intramolecular hydrogen bonds within individual diethylenetriamine molecules, by the ability to form intermolecular hydrogen bonds between the molecules of the SDA and by the solvation of these molecules by water. 

Basso A, Spizzo P, Toniutti M (2006) Kinetically controlled synthesis of ampicillin and cepa-halexin in highly condensed systems in the absence of a Uquid aqueous phase. J Mol Cattil B Enzym 39 105-111... 

Bisswanger H (2004) Practical enzymology. Wiley VCH, Weinheim, 272 pp Bjdrup P, Adlercreutz P, Clapes P (1999) Useful methods in enzymatic synthesis of peptides. A comparative study focussing on kinetically controlled synthesis of Ac-Phe-Ala-NHz catalyzed by oc-chymotiipsin. Biocatal Biotransfor 17 319-345 Black M, MiUer R (2006) Platform chemicals from crops. J Chem Technol Biotechnol 81(11) 1725-1728... 

Illanes A, Fajardo A (2001) Kinetically controlled synthesis of ampicUlin with immobiUzed penicillin acylase in the presence of organic cosolvents. J Mol Catal B Enzym 11 587-595 Illanes A, Rossi MC (1980) Induccion de celulasas de Trichoderma reesei en medios de cultivo definidos. Rev Arg Microbiol 12 79-86... 

The kinetically controlled synthesis of peptides (KCS) with proteases can be represented by the following scheme (Bordusa 2002) ... 

Abraham EP, Newton GGE (1961) The structure of cephalosporin C. Biochem J 79(2) 377-393 Aguirre C, Toledo M, Medina V et al. (2002) Effect of cosolvent and pH on the kinetically controlled synthesis of cephalexin with immobilised penicillin acylase. Proc Biochem 38(3) 351-360... 

The choice of a thermodynamically or kinetically controlled synthesis not only has important implications for the study of the reaction conditions, but also on the development of the enzyme, the reactor and even on the downstream processing, as ISPR (in situ product removal) will be important (see Table 1). 

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