Polypeptides, catalysis syntheses

The combination of carboxyl activation by a carbodiimide and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols.10 The reaction proceeds at room temperature. Carbodiimides are widely applied in the synthesis of polypeptides from amino acids. The proposed mechanism for this esterification reaction involves activation of the acid via isourea 28 followed by reaction with another acid molecule to form anhydride... 

The desire to produce enantiomerically pure pharmaceuticals and other fine chemicals has advanced the field of asymmetric catalytic technologies. Since the independent discoveries of Knowles and Homer [1,2] the number of innovative asymmetric catalysis for hydrogenation and other reactions has mushroomed. Initially, nature was the sole provider of enantiomeric and diastereoisomeric compounds these form what is known as the chiral pool. This pool is comprised of relatively inexpensive, readily available, optically active natural products, such as carbohydrates, hydroxy acids, and amino acids, that can be used as starting materials for asymmetric synthesis [3,4]. Before 1968, early attempts to mimic nature s biocatalysis through noble metal asymmetric catalysis primarily focused on a heterogeneous catalyst that used chiral supports [5] such as quartz, natural fibers, and polypeptides. An alternative strategy was hydrogenation of substrates modified by a chiral auxiliary [6]. 

The authors next turn to the structure and composition of the ribosome, a molecular machine that coordinates charged tRNAs, mRNA, and proteins, leading to protein synthesis. The fact that the ribosome is now recognized to be a ribozyme, with the RNA components playing the major role in catalysis, is introduced. The experiments that showed the polarities of polypeptide formation and the translation of mRNA are presented next. Then initiation is described, and the roles of a specialized... 

The synthesis of the protected tetrapeptide Ph-Ala-Gly-Val by rearrangement of the nitrone function to the corresponding oxaziridines has been reported. In turn oxaziridines rearrange to the amide, generally under acid catalysis. This is a significant example of the application of a well known reaction into a practical synthetic methodology. In what appears to be a seminal paper, opening new perspectives for the synthesis of polypeptides, the proof of concept of this method has been achieved, with the indication that several limitations of the present approach may be overcome. 

Another example of the increased reactivity of carboxylate ions is the catalysis by 18-crown-6 (28) of the loading of A -t-butyloxycarbonyl amino acid salts onto chloromethylated polystyrene (Equation 12) for Merrifield-type polypeptide synthesis. However, a less dramatic acceleration than expected was observed, possibly because of steric effects of the polymer backbone. Naked fluoride ion is another unusually strong nucleophile, but its enhanced basic character, although useful in some cases, may induce competing eliminations. ... 

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