Synthesis of Phosphoric Acids and their Derivatives

The ability of the calix[4]arene system to form cyclic phosphates has been demonstrated. When acted upon by PCI5, calixarene (8) (n = 0, R — = OH) 

Pyrolysis (at just above the melting point) of the distally diphosphorylated compound (9), and of the proximal diphosphate (10), and also of the tetraphos-phate, as well as of other compounds such as the trichloride (13), afforded the pyrophosphate (17), the structure of which was also confirmed by X-ray diffraction. The pyrolysis of partially phosphorylated derivatives of the terr-butyl-calix[6]arene also gave the bisbicyclic phosphate (16).  

The water-soluble distally phosphorylated calix[4]arenes (18) have been described as has the fully phosphorylated (19).  

D-2-Deoxy-m o-inositol l,3,4,5-tetrakis(dihydrogen phosphate) has been obtained from D-glucose and the synthesis and properties of racemic 6-deoxy- 

6-fluoro-myo-inositol l,4,5-tris(dihydrogen phosphate) have also been reported.  

1 Synthesis of Phosphoric Acids and their Derivatives. - Among various approaches to phosphate esters the phosphorylation of phenols with dialkyl cyanophosphonate and the synthesis of triaryl phosphates under phase-transfer conditions are worthy of mention. Mixed trialkyl phosphates are also reported to be formed by brief cathodic electrolysis of the reaction of dialkyl phosphonates with aromatic aldehydes and ketones, presumably by rearrangement of the initial a-hydroxy compounds. Further reports have appeared of the generation of metaphosphates by various methods. The synthesis of analogues 1 of famesyl pyrophosphate which incorporate photoactive esters has been reported both compounds are competitive inhibitors of farnesyl transferase. 

Numerous reports of the synthesis of cyclic analogues have appeared. The cyclophosphamidic chloride 2 has been prepared as a single enantiomer and 

Organophosphorus Chemistry, Volume 29 The Royal Society of Chemistry, 1999 

Interest in phosphorus-containing calixarenes continues. Structures reported include hexa(diethoxyphosphoryloxy)calix[6]arene (8), inherently chiral 1,2-bridged calix[4]arene diphosphates, and a calixarene like C3 symmetric receptor with a phosphate function at the cavity bottom. The purification of phosphate substituted calixarenes has been studied by chiral HPLC and by normal reverse phase HPLC. Mono(6-0-diphenoxyphosphoryl)-P-cyclodextrin (9) and mono(6-0-ethoxyhydroxyphosphoryl)-p-cyclodextrin (10) have been synthesised and show enantioselective inclusion of D and L amino acids e.g. 3.6 for D/L serine in the case of 9).  

A number of P(V) acid containing dendrimers have been synthesised. Examples include those starting from a hexachlorotriphosphazene core, e.g. 11 which could be complexed with iron or tungsten compounds, compounds up to seven generation possessing terminal P(S)(N-allyl2)Cl fragments which can be further 

Reagents i, (f )-Alpine borane, THF, H2O ii, (EtO)2PCi, py. CH2CI2 iii, Bu4N )3, MeCN 

Further work on various saccharide phosphates associated with the Leish- 

The preparation of inositol and structurally related phosphates continues to be actively explored. Examples include the first total synthesis of the inositol tetraphosphate enantiomeric pair, Ins(l,2,3,4)P4 (27) and Ins(l,2,3,6)P4 (28). Compounds (27) and (28) were dephosphorylated by a number of different enzymes and thus provide routes to specific inositol triphosphates. A number of myo-inositol 1,4,5-triphosphates, e.g. (29)-(32), modified at the 6-position have been prepared. All such derivatives investigated showed poor affinity for Ins(l,4,5)P3 receptors. A new and comparatively convenient synthesis of I-d-6-0-(2-amino-2-deoxy-a-D-glycopyranosyl)-chiro-inositol 1-phosphate (33) and the corresponding 1,2-cyclic phosphate (34) has been reported. The first examples of poly(ethylene glycol)-linked dimers (35) of D-myo-inositol 1,4,5-triphosphate have been prepared as probes for multi-subunit binding proteins for 

A number of phosphates, e.g. (37), which act as inositol monophosphatase inhibitors have been synthesised from the l,6-epoxy-4-benzyloxycyc-lohexan-2-ol (36)7 Conduritol derivatives (39) are useful synthetic building blocks. However, the enantioselective palladium-catalysed allyl alkylation and similar reactions of (38) are complex due to C2 symmetry. It has now been reported that dynamic kinetic asymmetric transformation (DYKAT) of racemic 

The synthesis of phospholipids and analogues, mainly by well-established methods, continues to be actively pursued. A new, stereospecific route to functionalised ether phospholipids, e.g. (54) and (55), as analogues of l-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) and modulation phospholipids, has been reported. The route uses (/ )-glycidyl tosylate (56) as the chiral precursor 

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Synthesis of Phosphoric Acids and Their Derivatives. - The individual Rp-and Sp- isomers of the organophosphate triesters (1-6) were synthesized and isolated on a preparative scale through the kinetic resolution of racemic mixtures via the hydrolysis of a single enantiomer by the bacterial phosphotriesteraze (PTE).i... 

Synthesis of Phosphoric Acids and Their Derivatives. A selective and mild synthetic route to long or functionalized chained dialkyl phosphates (l)-(5) has been reported (Figure 1). ... 

Synthesis of Phosphoric Acids and Their Derivatives. - A series of monoalkyl and dialkyl phosphorus acid chiral esters have been synthesised for use as carriers for the transport of aromatic amino acids through supported liquid membranes. The compounds acted as effective carriers but enantio-separation was at best moderate. A range of phosphono- and phosphoro-fluoridates have been prepared by treatment of the corresponding thio- or seleno- phosphorus acids with aqueous silver fluoride at room temperature (Scheme 1). In some cases oxidation rather than fluorination occurred. Stereospecifically deuterium-labelled allylic isoprenoid diphosphates, e.g. (1), have been synthesised from the corresponding deuterium-labelled aldehyde by asymmetric reduction, phosphorylation and Sn2 displacement with pyrophosphate (Scheme 2). ... 

Synthesis of Phosphoric Acids and their Derivatives.-New approaches to the preparation of dialkyl phosphorofluoridates include the treatment of a vinyl phosphate, e.g.,(l), or an irninophosphace, e.g.,(2), with triethylamine tris(hydrogen fluoride) when the alkyl group consists of a suitably protected nucleoside, the reaction between mono(crimethylsilyl) phosphite in pyridine and sulphuryl chloride fluoride at -30° has been successfully explored. Dibenzyl phosphorofluorldate, hitherto unreported, has been obtained from tecrabenzyl diphosphate and caesium fluoride, and also from the reaction between dibenzyl hydrogen phosphate and 2-fluoro-N-methylpyridinlum tosylate. ... 

Synthesis of Phosphoric Acids and their Derivatives.—Cyclic phosphoric acids (15) possessing 6-, 7-, or 8-membered rings are conveniently prepared by means of the reactions outlined in Scheme 1. ... 

Synthesis of Phosphoric Acids and their Derivatives.--The use of sulphuryl... 

In this subsection synthesis, reactions and biological aspects of phosphorus acids and their derivatives of the general formula (R0)2P(0)0R, (RO)2-P(NR )0R (R0)2P(S)SR (R0)2P(0)SR (R0)2P(0)NR r (R2N)2P(Se)NR 2 are described. Two subsubsections have been added concerning miscellaneous applications other than biological and use of phosphoric acids and their derivatives as catalysts. 

Phosphoric acids and their derivatives as catafysts Catalytic asymmetric transformations have become an essential part of contemporaiy organic synthesis. Over the past decades, the field of organocatalysis has emerged and grown dramatically with many new applications. In this wide area, chiral phosphoric acids as Bronsted acids... 

The use of chiral phosphoric acids and their derivatives (e.g., 117-119) has recently emerged [7] as a novel method for the stereoselective spirocychzation of simple dihydropyrans. These Br0nsted acids act as bifunctional catalysts, providing both acidic and basic sites for complexation to the electrophile and nucleophile, respectively (Fig. 2). Two studies using such catalysts for the stereoselective synthesis of spiroacetals have been reported. 

In the past year, the development of chemistry of phosphoric acid derivatives has been connected mainly with the topic of synthesis for biological applications. In this section, there will be discussed syntheses of various biological molecules in the form of free phosphoric acids and their salts as well as amide, diester or dithioster derivatives. 

Phospholipides.— Lecithin and other phospholipides of the diet are important nutritional somces of choUne and of phosphoric acid, and are resolved into their components by the esterases of the small intestine previous to absorption. Within the intestinal mucosa, a re-synthesis occiun, or a new phospholipide is assembled containing units derived from the saponified fats of the diet, and as such participates in the lipide transport in the lymph and the portal blood. By use of a phosphate containing a radioactive isotope of phosphorus as indicator, Artom and his colleagues (1937) have shown that phospholipides of the lecithin and cephalin type are synthesised in large quantities during fat absorption, and accumulate in the intestinal mucosa, the liver, and to a lesser extent, the kidney, but not in the spleen, heart or skeletal muscles. 

Thiotraamidophosphoric acids (35) are isoelectronic with phosphoric acids and were initially reported from the reaction of phosphorus pentasulfide with primary amines at high temperatures.62 Subsequently, an improved synthesis for 35 with increased yields and milder conditions has been reported involving the room temperature reaction of thiophosphoryl chloride and primary amines (Equation 50).63 The most convenient route to the analogous selenium derivatives SeP(NHPh)3 is from the oxidation of P(NHPh)3 with elemental selenium (Equation 51).63 Also isoelectronic with phosphoric acids are dithio wamido-phosphoric acids (36), which can be prepared from the reaction of phosphorus pentasulfide with an excess of primary amine at 30°C in toluene (Equation 52).62 The selenium derivatives of 36 can be prepared in a similar reaction from phosphorus (V) selenide, although due to their increased acidity... 

Nucleoside 5 -phosphates are employed as starting materials to prepare the activated derivatives (56). Their synthesis has been discussed in a Chapter in this Series.266 The methods used most frequently for preparing glycosyl phosphates involve the interaction of protected glycosyl bromides with diphenyl phosphate and subsequent removal of the protective groups,267 or by fusion of the peracetylated monosaccharides with anhydrous phosphoric acid.268... 

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