Phosphate monoesters synthesis

Trimethylsilyl)ethanol has been used as a protecting group in phosphate monoester synthesis and involves the use of 2-(lrimethylsilyl)ethyl dichlorophosphite (eq 14). Bis[2-(trimethylsilyl)ethyl] (V,(V-diisopropylphosphoramidite has been prepared from dichloro(diisopropylamino)phosphine and 2-(trimethylsilyl) ethanol and used as a phosphitylating agent in the synthesis of phosphotyrosine containing peptides (eq 15). ... 

The general route developed for the synthesis of chiral [160,170, 80]phosphate monoesters of known absolute configuration is shown in Scheme 1 (1). ... 

Scheme I. Synthesis of[(S)-,60, 17O, lsO phosphate monoesters Reagents i, PhU ii, HOCH2CH2OH, p-MeC6H4S03H Hi, H2laO, dioxan, p-MeC6H4S03H iv, LiAlH4 v, P 7OCI3, CSHSN ROH. CdUN vi, H2, Pd/C.

Introduction of a phosphate monoester and removal of its protecting groups was a serious impediment in a synthesis of the serine-threonine phosphatase inhibitor Calyculin A by Evans and co-workers [Scheme 7,22].38 The four phosphate protecting groups evaluated were 2-cyanoethyl and 2-(trimethylsi]y])ethyl (see below), benzyl and p-methoxybenzyl. Of these, the p-methoxybenzyl phosphate ester offered the best compromise between base stability (it survived a Wittig reaction in the presence of a metal amide base) and acid lability required for the final deprotection step in which three secondary terf-butyldimethylsiiyl... 

Tetrabutyiammonium fluoride is very effective for the cleavage of 2-(trimethyl-silyl)ethyl phosphate monoesters. A salient example comes from a synthesis of a partial structure of Agrocin 84 with its very sensitive glucofuranosyl phos-... 

Full details of the synthesis of unsymmetrical diesters of pyrophosphoric acid by the reaction of the disilver salt of a monoester of phosphorothioic acid and a phosphate monoester have been published. In view of the good yields, the mild conditions, and the absence of symmetrical pyrophosphate byproducts it appears to be superior to previous routes to the nucleotide pyrophosphate coenzymes. Further, the findings that the procedure is insensitive to... 

Inorganic pyrophosphate may be considered as a particular case of a phosphate monoester. The enzymatic decomposition of pyrophosphate by inorganic pyrophosphatase (Table 13-6, entry 10) can be used to drive a multienzyme synthesis (see1351). 

A. Synthesis of Phosphate Monoesters Chiral by Virtue of Oxygen Isotopes. 99... 

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... 

Methods for the synthesis of phosphate monoesters and phosphoramidates of carbohydrates and nucleic acids have been reviewed. ... 

The mechanism of the phosphorylating species involved in dicy-clohexylcarbodiimide (DDC)-promoted nucleic acid synthesis has been investigated by using a polymeric support (Blackburn et ai, 1966). Polystyrenes containing hydroxyl groups (benzyl and phenethyl alcohols) were phosphorylated with DCC and j8-cyanoethylphosphate, whereas the equivalent polymers containing the phosphate monoester (( (CH2) OPOsH, = 1,2) did not yield any diester with DCC and a soluble alcohol. The results suggested that, in contrast to the mesitylene sulfonyl chloride-promoted condensation, DDC-promoted condensation involved a trimetaphosphate intermediate. 

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