Synthesis of Phosphate Esters

The use of phosphorus oxychloride for the synthesis of phosphate esters of sugars 160) has been largely replaced by dibenzyl 161) and diphenyl phosphorochloridates 162), The latter reagent may be prepared in a pure, stable form which reacts readily with an alcohol in pyridine at low temperature. The phenyl groups may be removed from the resulting di-0-phenyl phosphate derivative of the alcohol by catalytic hydrogenation employing a platinum catalyst. 

Phenyl phosphorodichloridate 163) is useful in the synthesis of asymmetric phosphate diesters such as that of the phosphatide shown below. 

Inorganic phosphate reacts with epoxides to give phosphate esters. This method 164) is particularly useful for the preparation of D-glucose 6-phosphate labeled with the isotope P .  

They also can be synthesized by coupling the poly-O-acetylglycosyl bromide with monosilyer phosphate as the phosphorylating agent 1686), 

Enzymic syntheses of a-D-glucose 1-phosphate from starch by the action of phosphorylase 169) and of n-glucose 6-phosphate from readily available D-fructose 1,6-diphosphate have been described 170), 

---

Fluormated organosilanes are used as reagents for the construction of carbon-carbon bonds and for the selective synthesis of phosphate esters... 

Nearly all synthesis of phosphate esters, phosphorothioates and phosphoroamidoates use as starting materials one of the following... 

A novel procedure has been developed for the synthesis of phosphate esters of hindered alcohols, and was designed to avoid nucleophilic displacement reactions. It involves photolysis of the alkyl nitrite in the presence of a trialkyl phosphite and proceeds by addition of the alkoxyl radical to phosphorus followed by elimination of an alkyl group (Scheme 3). ... 

Given the low natural abundance of O and 0, chemical methods for the synthesis of phosphate esters that are chiral by virtue of oxygen-isotope substitution must allow for the introduction of any oxygen isotope from (ideally) the commercially available forms of the heavy isotopes H2O, CO2, or O2. In addition, the substrates of the phosphoryl and nucleotidyl transfer reactions include three types of structurally and chemically different phosphates, almost all of which are polyhydroxylic phosphate monoesters, such as sugar phosphates and mononucleotides, phosphate diesters, such as 3, 5 -cyclic nucleotides and oligonucleotides, and phosphate anhydrides... 

The preparation of phosphate esters has been reviewed and full details have appeared of the use of 2-chloromethyl-4-nitrophenyl esters (reported last year) in the synthesis of monoesters and mixed dialkyl esters of phosphoric acid. 

The synthesis of organophosphate ester compounds dates to the mid-1800s. From an early date, the most commercially useful compounds for lubricants, plasticizers, and hydraulic fluids were in the chemical family of the tertiary esters. Before 1970, products were introduced based on alkyl aryl phosphates that... 

Hata, T. and Sekine, M., Silyl- and stannyl-esters of phosphorus oxyacids — intermediates for the synthesis of phosphate derivatives of biological interest, in Phosphorus Chemistry Directed Toward Biology, Stec, W.J., Ed., Pergamon, New York, 1980, p. 197. 

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. 

From this brief survey, it is seen that there were few features of carbohydrate metabolism in plants that escaped Hassid s touch, and much that we now know about the role of sugar nucleotides in the interconversion of carbohydrates in plants is a direct result of his persistent effort. From the incorporation of labelled precursors into monosaccharides, to the conversion of the monosaccharides into their glycosyl phosphates, to the action of the pyrophosphorylases in the synthesis of glycosyl esters of nucleoside pyrophosphates, to the interconversion of the resulting sugar nucleotides, to the polymerization of the activated monosaccharides to yield disaccharides and the homopolysaccharides, and, finally, to the modification of the polysaccharides by methylation—in summary, to almost every aspect... 

The year s reviews cover phosphorylated indoles, phosphorus-selenium compounds, phosphoryl carbenes, phosphorus-sulphur compounds, and steroid phosphates, as well as the synthesis of phosphorus esters via oxyphosphoranes. A review on phosphonates contains many interesting applications of some of the well-tried syntheses of these as analogues of natural phosphates. ... 

Corey and Wright have utilized reductive conversion of a vinyl diethyl phosphate (73) to an alkene 74 in a synthesis of colneleic ester via the enol esters 72.43... 

The reaction of phosphorous esters and amides with polyhalogeno-methanes has been studied and used in a synthesis of phosphates. The reaction of diphenyl phosphorochloridate (103), produced in situ from diphenyl phosphonate and carbon tetrachloride, has been studied with various diamines. ... 

The reaction of alkoxyl radicals (generated by photolysis of nitrite esters) with phosphites has been exploited in a new synthesis of phosphates of hindered alcohols. Another aspect of this radical reaction which has been investigated, has been an evaluation of the ease of )8-cleavage of axial and... 

Tanaka (293) has applied this method to the synthesis of a variety of phosphate esters, including some of biological importance. 

Further developments in the. synthesis of phosphate and thiophosphate esters from myo-inositol (10) have been widely described. By and large, these syntheses have followed the procedures and used reagents (particularly with regard to the nature of protection... 

Chlorination of dialkylphosphites with NCS affords the corresponding dialkylchlorophosphate. The dialkylchlorophosphates generated react with alcohols to give phosphonate esters. The direct chlorination of dihenzylphosphite with NCS was used in the synthesis of phosphate prodrugs of the anti-HIV drug 3 -azido-2, 3 -dideoxythymidine (AZT) (eq 32). ... 

---