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A new method of phosphorylation and the synthesis of some phosphate esters of biological interest

University of British Columbia

Tetra-p-nitrophenyl pyrophosphate, generated in situ by the reaction of di-p-nitrophenyl phosphate with di-p-tolyl carbodiimide in anhydrous dioxane, has been shown to be a new and powerful phosphorylating agent, it has been used for the phosphorylation of various aliphatic alcohols and carbohydrate derivatives, particularly nucleosides, as well as of aliphatic amines and mercaptans. The removal of the protecting groups from the initially formed di-p-nitrophenyl alkyl phosphates has been accomplished by both alkaline hydrolysis and catalytic hydrogenolysis. Various other chemical reactions of the intermediate neutral esters, as typified by di-p-nitrophenyl methyl phosphate, have been studied in considerable detail. Included in these are: mild alkaline hydrolysis, partial hydrogenolysis, the action of anhydrous amines, acidic hydrolysis, base catalysed transesterification, and reductive cleavage with sodium in liquid ammonia. The method has been specifically applied, to the phosphorylation of 2',3'-0-isopropylidine guanosine and has led to the first efficient synthesis of the biologically interesting guanosine-5'-phosphate. Also the enzymatic-ally useful guanosine-5’-mono-p-nitrophenyl phosphate and uridine-5’-mono-p-nitrophenyl phosphate have been prepared and the formation of 3,5’-cyclo-guanosine quaternary salts observed. Several synthetic routes have been developed for the synthesis of 1,2-0-isopropylidine-D-xylofuranose-3,5-cyclic phosphate and of D-xylofuranose-3,5-cyclic phosphate. Hot alkaline hydrolysis of the former followed by acidic removal of the isopropylidine group has led to a mixture of D-xylofuranose-5-phosphate and D-xylopyranose-3-phosphate which were separated by ion exchange chromatography. Both products have been fully characterized and the method constitutes the first successful synthesis of D-xylose-3-phosphate. A previously reported isolation of the latter compound has been reexamined and shown to be in error. Reinterpretation of the data has shown the reported compound to be in fact D-xylulose-5-phosphate.

Text

2012-01-31

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http://hdl.handle.net/2429/40394

Chemistry

University of British Columbia

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