9- phosphate ester, synthesis

Phosphate ester synthesis and properties have been reviewed earlier [1,10-13]. The current treatise will consequently concentrate on manufacturing techniques with special emphasis on recent advances in preparing high monoalkyl phosphate (MAP) and high dialkyl phosphate (DAP) esters. 

Analog of HTIB. Various derivatives of HTIB with substituents in the iodoarene nucleus, ArI(OH)OTs, and three arenesnlfonyloxy analogs have been reported. [Hydroxy (mesyloxy)Iodo] benzene, PhI(0H)03SMe, and [hydroxy((+)-10-camphorsulfonyloxy)iodo]benzene are also known. [Hydroxy ((bis (pheny loxy) phosphoryl) oxy) iodobenzene], PhI(0H)0P(0)(0Ph)2, shows considerable potential for phosphate ester synthesis. Thus far, the a-oxyphosphorylation of ketones and -dicarbonyl compounds, the oxyphosphoryllac-tonization of alkenoic acids, and the conversion of terminal alkynes to monoketol phosphates with HPIB have been reported. 

Holmes, R.R., Day, R.O., Yoshida, Y. and Holmes, J.M., Hydrogen-bonded phosphate-esters - synthesis and structure of imidazole-containing salts of diphenyl phosphate and (trichloromethyl)phosphonic acid, J. Am. Chem. Soc. 114 (5), 1771-1778 (1992). 

Much effort has been placed in the synthesis of compounds possessing a chiral center at the phosphoms atom, particularly three- and four-coordinate compounds such as tertiary phosphines, phosphine oxides, phosphonates, phosphinates, and phosphate esters (11). Some enantiomers are known to exhibit a variety of biological activities and are therefore of interest Oas agricultural chemicals, pharmaceuticals (qv), etc. Homochiral bisphosphines are commonly used in catalytic asymmetric syntheses providing good enantioselectivities (see also Nucleic acids). Excellent reviews of low coordinate (coordination numbers 1 and 2) phosphoms compounds are available (12). 

Fluormated organosilanes are used as reagents for the construction of carbon-carbon bonds and for the selective synthesis of phosphate esters... 

Three types of synthases catalyze the addition of phosphoenolpyruvate (PEP) to aldoses or the corresponding terminal phosphate esters. By concurrent release of inorganic phosphate from the preformed enolate nucleophile, the additions are essentially irreversible. None of the enzymes are yet commercially available and little data are available oil the individual specificities for the aldehydic substrates. A bacterial NeuAc synthase (EC 4.1.3.19) has been used for the microscale synthesis of A -acetylncuraminic acid from Af-acetyl-D-mannosamine31 and its 9-azido analog from 2-acetamido-6-azido-2,6-dideoxy-D-mannose32. 

Furthermore, the GPO procedure can also be used for a preparative synthesis of the corresponding phosphorothioate (37), phosphoramidate (38), and methylene phosphonate (39) analogs of (25) (Figure 10.20) from suitable diol precursors [106] to be used as aldolase substrates [102]. In fact, such isosteric replacements of the phosphate ester oxygen were found to be tolerable by a number of class I and class II aldolases, and only some specific enzymes failed to accept the less polar phosphonate (39) [107]. Thus, sugar phosphonates (e.g. (71)/(72)) that mimic metabolic intermediates but are hydrolytically stable to phosphatase degradation can be rapidly synthesized (Figure 10.28). 

The preparation of phosphate esters has been reviewed and full details have appeared of the use of 2-chloromethyl-4-nitrophenyl esters (reported last year) in the synthesis of monoesters and mixed dialkyl esters of phosphoric acid. 

Figure 7 A novel, phosphate ester linking strategy [22] was used in the synthesis of phenyl phosphate-containing compound libraries, accomplished in 96-deepwell reaction blocks [23], Rigid, nonpeptide templates (A-group) and pY+3 substituents (B-group) satisfied the diversity sites of the molecules.

Scheme 3.5, and carotenoids have been previously incorporated into vesicles of phospholipids, Figure 3.1 (Milon et al. 1986, Britton 1998). It was therefore reasonable to connect carotenoids with a phosphate group, above all because hydrophobic phosphate esters had previously been synthesized (Sliwka 1997). The C30-monoglyceride, 3.12, was therefore used as an educt for the synthesis of the zwitterionic, hydrophobic C30-lysophosphocholine, 3.15, via aminolyse of the bromo phosphoester,... 

The synthesis of the nucleotides requires both a source of phosphate and a means of activating the phosphate group so that phosphate esters can be formed. There are three possible sources of phosphorus on the early Earth as well as from meteorites (Figure 8.9). 

Sugiyama, M., Hong, Z., Whalen, L.J., Greenberg, W.A. and Wong, C.-H., Borate as a phosphate ester mimic in aldolase-catalyzed reactions practical synthesis of L-fructose and L-iminocyclitols. Adv. Synth. Catal. 2006, 348, 2555 - 2559. 

A practical, inexpensive one-step procedure was developed for the RhaD-catalyzed gram-scale synthesis of L-fructose. The requirement for DHAP as the donor substrate was circumvented by use of borate buffer, presumably by in situ formation of borate esters as a phosphate ester mimic. Racemic glyceraldehyde was also used, as the enzyme preferentially accepted the L-enantiomer as a substrate. The method can also be apphed to other products, including L-rhamnulose, and towards a two-step synthesis of L-iminocychtols. ... 

ATP synthesis is achieved by ADP acting as the nucleophile towards this mixed anhydride, attacking the P=0 bond, with the carboxylate being the leaving group. Note that this reaction is favoured, whereas the alternative possibility involving hydrolysis of the phosphate ester does not occur. This is precisely what we would predict knowing the different reactivities of anhydrides and esters (see Section 7.8). This direct synthesis of ATP by a process in which... 

The above reagents serve as condensing reagents and have different reactivities for peptides 279, p-lactams 281, esters, thioesters, and mixed phosphates, as well as for the direct preparation of 3-acyl-2(3F/)-oxazolones. The bis(2-oxo-3-oxazohnyl)phosphinate 282 is useful for Zr(IV)-catalyzed phosphorylation of alcohols, leading to the general synthesis of acid- and base-labile mixed phosphate esters 284 (Fig. 5.67). ... 

A major advancement in the Fmoc-based solid-phase synthesis of Tyr(P)-peptides was realized with the Fmoc-Tyr[PO(OR1)2]-OH derivatives 7 (R1 = Bzl, tBu, Mdpse) [Mdpse = 2-(methyldiphenylsilyl)ethyl] in which the acid-labile phosphate esters offered simple cleavage by TFA treatment. While the initial difficult synthesis of derivatives 7 restricted general synthetic usage, the subsequent commercial availability of these derivatives and their compatibility with solid-phase synthesis has provided a simple and efficient procedure for the routine synthesis of large complex Tyr(P)-peptides. 

Boc-Based Solid-Phase Synthesis Using Aiyl Phosphate Ester Protection... 

The synthesis of Abu[PO(OH)2]-peptides is also accomplished via the use of Fmoc-Abu-[PO(OAl)2]-OH (22) with the allyl phosphate ester being cleaved by Pd(0)-mediated treatment. Fmoc-Abu[PO(OAl)2]-OH (22)t101] is prepared from Schollkopfs (-)-bislactim ethyl ether 21f102] by a four-step procedure that involves initial treatment of the lithium salt of... 

---