Phosphate, as leaving group

The reaction occurs by two sequential nucleophilic acyl substitutions, the first by a cysteine residue in the enzyme, with phosphate as leaving group, and the second by hydride donation fromNADH, with the cysteine residue as leaving group. 

Vankayalapati, H, Singh, G, Stereoselective synthesis of a-L-Eucp-(l,2)- and -(l,3)-p-D-Galp(l)-4-methylumbelliferone using glycosyl donor substituted by propane-1,3-diyl phosphate as leaving group, J. Chem. Soc. Perkin. Trans. L, 2187-2193, 2000. 

It s this ability to drive otherwise unfavorable phosphorylation reactions that makes ATP so useful. The resultant phosphates are much more reactive as leaving groups in nucleophilic substitutions and eliminations than the corresponding alcohols they re derived from and are therefore more likely to be chemically useful. 

Catalysis by adenylyl cyclases involves cation-mediated attack of the 3 -OH on the a-phosphate of 5 -ATP, with PPj as leaving group. It is a reversible Adenylyl Cyclases. Figure 3 Membrane localization, bireactant sequential mechanism with free cation and topology, and regulation of mammalian adenylyl cyclases. cation 5 -ATP as substrates and cAMP, cation-PP , and... 

The nucleotide cyclic AMP (3, 5 -cyclic adenosine monophosphate, cAMP) is a cyclic phosphate ester of particular biochemical significance. It is formed from the triester ATP by the action of the enzyme adenylate cyclase, via nucleophilic attack of the ribose 3 -hydroxyl onto the nearest P=0 group, displacing diphosphate as leaving group. It is subsequently inactivated by hydrolysis to 5 -AMP through the action of a phosphodiesterase enzyme. 

T. J. Martin and R. R. Schmidt, Efficient sialylation with phosphites as leaving group, Tetrahedron Lett. 33 6123 (1992) T. J. Martin, R. Brescello, A. Toepfer, andR. R. Schmidt, Synthesis of phosphites and phosphates of neuraminic acid and their glycosyl donor properties— convenient synthesis of GM3, Glycoconjugate J. 70 16 (1993), and references therein. 

Putting on the phosphate is tricky too and more protection is necessary. This phosphorus compound with one chloride as leaving group and two benzyl esters as protecting groups proved ideal. The benzyl esters can be removed by hydrogenation (Chapter 24) and the acetal by treatment with dilute acid to give AMP. 

Many further examples of reactions in which phosphate anions act as leaving groups have been reported. Palladium-catalysed reactions of cyclic ketene acetal phosphates, e.g. 64, are reported to offer advantages over the corresponding... 

Trimethyl phosphate can serve as leaving group in the MIRC reaction. An example is the formation of 14 and 15. 2,2,2-Trimethoxy-l,3,2-dioxaphosphole was reacted with benz-ylidenemalononitriles to afford 2-acyl-1,1-dicyanocyclopropanes from the initially formed betaines.In an analogous way, cyclopropanes 16 were obtained under very mild conditions from betaines by expulsion of hexamethylphosphoric triamide. In this case, the betaine was prepared by reaction of tris(dimethylamino)phosphane with a 1,2-diketone or a-keto ester. 

Additionally, and similar to the previously discussed Stille reaction, various leaving groups have been employed in Suzuki cross-coupling reactions. The Suzuki reaction can be carried out with bromides, iodides, and, usually with slightly lower yield, chlorides. Triflates and related sulfonates are perfectly suited to act as leaving groups, and occasionally, the application of diazonium salts or phosphates has been reported [63]. 

The catalytic effects of the alkali-metal ions in the ethanolysis of 4-nitrophe-nyl diphenyl phosphate (23) with 4-nitrophenoxide as leaving group reveals the... 

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