Phosphate esters introduction

In keeping with its biogenetic origin m three molecules of acetic acid mevalonic acid has six carbon atoms The conversion of mevalonate to isopentenyl pyrophosphate involves loss of the extra carbon as carbon dioxide First the alcohol hydroxyl groups of mevalonate are converted to phosphate ester functions—they are enzymatically phosphorylated with introduction of a simple phosphate at the tertiary site and a pyrophosphate at the primary site Decarboxylation m concert with loss of the terti ary phosphate introduces a carbon-carbon double bond and gives isopentenyl pyrophos phate the fundamental building block for formation of isoprenoid natural products... 

Phosphonate analogs to phosphate esters, in which the P—0 bond is formally replaced by a P—C bond, have attracted attention due to their stability toward the hydrolytic action of phosphatases, which renders them potential inhibitors or regulators of metabolic processes. Two alternative pathways, in fact, may achieve introduction of the phosphonate moiety by enzyme catalysis. The first employs the bioisosteric methylene phosphonate analog (39), which yields products related to sugar 1-phosphates such as (71)/(72) (Figure 10.28) [102,107]. This strategy is rather effective because of the inherent stability of (39) as a replacement for (25), but depends on the individual tolerance of the aldolase for structural modification close... 

A further test of the stereoelectronic theory of reactivity of phosphate esters has been attempted using measurements of the rates of displacement of 4-nitrophenate from the esters (23) and (24), their phosphorus epimers, and also (25), in aqueous methanol the introduction of the 4a-Me group into the system would, it was hoped, reduce the the flexibility of the bicyclic structures and so possibly eliminate the participation of twist-boat conformations. The presence of the 4a-Me group has no effect of the rate of displacement of the axial ArO group... 

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... 

Continuous-monitoring methods for assay of TR-ACP activity are based on the principle introduced by Hillmann in which a-naphthoi released from its phosphate ester forms a colored product with the stabilized diazonium salt of 2-amino-5-chlorotoluene-1,5-naphthalene disulfonate (Fast Red TR). The introduction of alcohols, such as 1,5-pen-tanediol, accelerates the reaction and increases sensitivity by acting as phosphate acceptors in transfer reactions. The addition of sodium tartrate inhibits the sensitive isoenzymes (i.e., prostatic and lysosomal ACPs) if they are present in the sample. 

Phosphorus chemistry and biochemistry are enormous topics, and obviously this essay touches on only a few aspects of the subject many other aspects are discussed in detail in this volume by others. This introduction to the symposium is built around the commanding importance of electrostatics in the chemistry and biochemistry of phosphates and phosphites, but that emphasis necessitated omitting a discussion of many other topics. These include, for example, pseudorotation in the hydrolysis of cyclic esters of phosphorus, a fascinating topic to which Edward Dennis and David Gorenstein and others in my laboratory have made significant contributions (28). The brilliant work of Usher, Richardson and Eckstein (29) which (if you will pardon a pun) ushered in the determinations of the stereochemistry at phosphorus in the reactions of phosphate esters, has been omitted, as has the work of Jeremy Knowles (30) and his coworkers, who demonstrated how to use 0 6, 0 7 and 0 8,... 

Because of concerns in the 1940s over the flammability of mineral and vegetable oil-based hydraulic fluids the civil aviation industry sought a fluid with greater fire resistance. The result was the introduction of a phosphate ester-based hydraulic fluid. These fluids contain in the region of 90% phosphate ester and are of the general structure (R0)3P=0, where R = butyl or isobutyl. 

In this chapter I will examine recent evidence for and against two chemically distinct mechanisms with two chemically distinct intermediates in the hydrolyses of phosphate esters. Early experimental evidence for these mechanisms and intermediates was discussed in the previously cited chapter in this series (/), and, as such, this introduction will only briefly summarize the fundamental chemical and stereochemical differences between these mechanisms. 

As noted in the introduction, the effects of multiple modes of catalysis are often multiplicative rather than simply additive. Consequently, it is not surprising that a number of hydrolytic metalloenzymes have evolved that utilize a constellation of three metal ions in catalysis. Perhaps not coincidentally, all well-characterized examples of this class catalyze the hydrolytic cleavage of phosphate ester or phosphoric acid anhydride bonds, which represent a difficult and long-standing chemical problem. In every case but one, the metal ions in the trimetal centers are all zinc. As we shall see, alkaline phosphatase utilizes a Zn2Mg trinuclear center. It should be pointed out that in the older literature many of the enzymes discussed in this section have been described as containing dinuclear metal centers. Only in the last few years has it become clear that three metal ions are present and participate in catalysis by these systems. 

The introduction of a phosphate moiety into a polyhydroxy compound by classic chemical methods is tedious since it usually requires a number of protection and deprotection steps. Furthermore, oligophosphate esters as undesired byproducts arising from overphosphorylation are a common problem. Employing enzymes for the regioselective formation of phosphate esters can eliminate many of these disadvantages thus making these syntheses more efficient. Additionally, enantioselective transformations are also possible involving the desymmetrization of prochiral or weso-diols or the resolution of racemates. 

Flame Retardant n (1947) A material that reduces the tendency of plastics to burn. Flame retardants are usually incorporated as additives during compounding, but sometimes applied to surfaces of finished articles. Some plasticizers, particularly the phosphate esters and chlorinated paraffins, also serve as flame retardants. Inorganic flame retardants include antimony trioxide, hydrated alumina, monoammonium phosphate, dicyandiamide, zinc borate, boric acid, and ammonium sulfamate. Another group, called reactive-type flame retardants, includes bromine-containing polyols, Chlorendic acid and anhydride, tetrabromo- and tetrachlorophthalic anhydride, tetrabromo bisphenol A, diallyl chlorendate, and unsaturated phosphonated chlorophenols. A few neat resins, such as PVC and the fluoro- and chlorofluo-rocarbons, are flame-retardant (Elias, H (2003) An introduction to plastics. Wiley, New York Modem plastics encyclopedia. McGraw-Hill/Modem Plastics, New York, 1986 1990, 1992, 1993 editions). See Flammability. 

---