Amino acids phosphate ester hydrolysis

The current review is of necessity selective. Over the two year period covered, there has been impressive advances in several areas of P(V) chemistry. For example, biological aspects of quinquevalent phosphorus acids chemistry continue to increase in importance. A wide variety of natural and unnatural phosphates including inositols, lipids, some carbohydrates and their phospho-nates, phosphinates and fluorinated analogues has been synthesized. Special attention has been paid to the synthesis of phosphorus analogues of all types of amino acids and some peptides. Numerous investigations of phosphate ester hydrolysis and related reactions continue to be reported. Interest in approaches to easier detoxification of insecticides continues. A number of new and improved stereoselective synthetic procedures have been elaborated. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. 

Novozymes, a subtilisin produced by Bacillus licheniformis, was used by Chen et al ° to carry out a dynamic kinetic resolution of benzyl, butyl, or propyl esters of DL-phenylalanine, tyrosine, and leucine. The hydrolysis was performed at pH 8.5 in 2-methyl-2-propanol/water (19 1) and the freed L-amino acids precipitated. The key feature bringing about continual racemization of the remaining D-amino acid esters was the inclusion of 20 mmol 1 pyridoxal phosphate. 

Amino acid ester side groups are not the only units that sensitize the system to hydrolysis. The imidazolyl group has an even greater effect.197-198-219 For example, polymer 3.86, prepared by the reaction of poly(dichlorophosphazene) with imidazole, is so unstable hydrolytically that it decomposes in moist air to imidazole, phosphate, and ammonia. This is too high a sensitivity for most biomedical applications. Hence, an emphasis has been placed on the study of polymers such as 3.87 in which a hydrophobic cosubstituent group, such as aryloxy, is present to reduce the rate of erosion. 

The synthesis of (-t-)-polyoxin J 14 is completed by selective ester hydrolysis with aqueous lithium hydroxide. The resulting carbamoylpolyoxamic acid was then coupled with the protected thymine polyoxin C 8 with the BOP reagent (Castro s reagent)14 (benzotriazol-1 -yloxytris(dimethyl-amino)phosphonium hexafluoro-phosphate) 37 to furnish the peptide derivative in 63 % yield. 

Histidine can be prepared from imidazole as in Scheme 117. It is a basic amino acid, the biosynthesis of which appears to involve adenosine 5 -phosphate, ribose phosphate and glutamine (which supplies a nitrogen for the imidazole ring) (Scheme 118). Histidine is one of the most important amino acids and has involvement in such biological processes as ester hydrolysis, acylation and (by virtue of its complexing power with iron) oxygen... 

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