Lowe synthesis, phosphate monoesters

Although phosphate monoesters chiral by virtue of oxygen isotope substitutions cannot be used in stereochemical studies of phosphate monoester hydrolysis (since there are only three stable isotopes of oxygen), they have been used profitably in studies of phosphoryl transfer reactions relevant to the question of the intermediacy of monomeric metaphosphate anion in phosphoryl transfer reactions (see Section III,A). The laboratories of Knowles and Lowe have reported general methods for the synthesis of phosphate monoesters chiral by virtue of oxygen isotope substitution, and these syntheses are summarized in this section. 

Simultaneously and independently, Cullis and Lowe developed a second general methodology for the synthesis of, 0, 0-labeled chiral phosphate monoesters (76, 77). This synthesis relies upon the synthesis of a cyclic hydrobenzoin triester of the alcohol or phosphoric acid followed by hydrogenolysis to liberate the isotopically labeled monoester product (Fig. 2). Hydrobenzoin, chiral by virtue of stereospecific labeling with 0 and 0, is the source of the two specified oxygen isotopes, and O is derived from H2 0 via P OCL. The reader is referred to the articles by Cullis and Lowe for details of the synthesis. 

Lowe, Cullis, and co-workers have described general methods for the synthesis of oxygen chiral phosphorothioate monoesters (see Figs. 3 and 4). The synthesis by Cullis is strictly analogous to the synthesis of chiral phosphate monoesters by Knowles except that (- )-ephedrine is thiophosphorylated with PSCI3... 

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... 

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