Phosphorodichloridates phosphorylation

Phosphorylation of cholesterol followed by the normal hydrolytic work-up gives the phosphate monoester, not the symmetrical pyrophosphate diester as previously claimed. Cholesteryl phosphorodichloridate and some related steroidal phosphorodichloridates have been prepared from the action of pyrophosphoryl chloride on the appropriate alcohol ... 

Several of these steroid derivatives underwent elimination of phosphorodichloridate anion, giving hydrocarbon products, rather than ester formation when treated with methanolic pyridine. Pyrophosphoric acid itself has been used to phosphorylate (2-hydroxymethyl)pyridine. ... 

G. B. Quistad, N. Zhang, S. E. Sparks, J. E. Casida, Phosphoacetylcholinesterase Toxicity of Phosphorus Oxychloride to Mammals and Insects That Can be Attributed to Selective Phosphorylation of Acetylcholinesterase by Phosphorodichloridic Acid , Chem. Res. Toxicol. 2000, 13, 652-657. 

Quistad, G.B. et al., Toxicity of phosphorus oxychloride to mammals and insects that can be attributed to selective phosphorylation of acetylcholinesterase by phosphorodichloridic acid, Chem. Res. Toxicol., 13, 652-657, 2000. 

The phosphorylation of free nucleosides using phosphoryl chloride in trimethyl-phosphate to give a nucleoside phosphorodichloridate is known as the Yoshikawa procedure4 (Protocol 5). Hydrolysis of this intermediate in aqueous TEAB provides a route to nucleoside 5 -monophosphates (Protocol 8) although it is mainly used to prepare nucleoside triphosphates, whereby pyrophosphate is reacted with the nucleoside intermediate (see Section 3.3 and Protocol 10). In practice, a compromise between formation of the 5 -phosphorodichloridate that is,... 

Following phosphorylation using the Yoshikawa procedure, the reaction of pyrophosphate with the intermediate phosphorodichloridate followed by aqueous work-up provides a convenient one-pot synthesis for triphosphates. With slight modification to this procedure, thiophosphoryl chloride can be used in place of phosphoryl chloride to give 5 -( 1 -thio)triphosphates as a mixture of two diaste-reoisomers (.S p and Rp). Both procedures require the prior preparation of the DMF-soluble, bis(tri-n-butylammonium) salt of pyrophosphate. This is prepared as a 0.5 M solution, can be stored in the fridge and is converted to its terrafcis(tri-n-butylammonium) salt immediately prior to reaction. Rates of nucleoside phosphorylation vary considerably and it is necessary to monitor the formation of the phosphorodichloridate during the Yoshikawa procedure in order... 

Cholesteryl phosphorodichloridate. Cholesteryl phosphorodichloridate (2) can be prepared in 87% yield by reaction of cholesterol (I) with phosphoryl chloride in the... 

Phosphorus oxychloride is a suitable reagent for preparation of the symmetrically substituted phospho-triesters of type (RO)3PO. The preparation is easily achieved by treatment of phosphorus oxychloride with 3 equiv. of alcohols or their metal salts. The reaction is generally promoted by a base or acid. Titanium trichloride is a particularly effective catalyst for the reaction. Conversion of POCI3 to unsymmetri-cally substituted phosphotriesters is achievable with difficulty. Phosphorochloridates and phosphorodichloridates have been used for the preparation of mixed tertiary phosphoric esters of type (ROlmPOfOROn (ffi = 1, n = 2, or m = 2, n = 1) in a very wide variety. Reaction of phosphorus oxychloride and 1 or 2 equiv. of alcohols followed by hydrolysis forms phosphomonoesters or phosphodi-esters, respectively. The hydrolysis may be generally effected by dilute aqueous alkali. Some phosphoFodichlori te intermediates are easily hydrolyzed by water. For example, the phosphorylation of a ribonucleoside (1 equation 4) with phosphorus oxychloride in an aqueous pyridine-acetonitrile mixture furnishes the nucleoside S -monophosphate (2) in excellent yield. ... 

Phosphorylation of nucleosides. Direct phosphorylation of unprotected nucleosides generally leads to a mixture of the three possible phosphates. However, treatment of 2, 3 -0-isopropylidene nucleosides with phosphoryl chloride gives. V-phosphorodichloridates in fair yield. The reaction is greatly improved by use of trimethyl phosphate, (CH30)3P0, ortriethyl phosphate, in which the substrates are moderately soluble. After hydrolysis, 5 -nucleotides are obtained in nearly quantitative yield.1 Adenine nucleosides, such as (1), are readily converted into the 3, 5 -cyclic monophosphate, such as (2), by this procedure.2... 

Polyfluoroalkyl phosphorodichloridates and bis(poly-fluoroalkyl) phosphorochloridates have been prepared from the corresponding alcohols. The reactions between polychloro-1-nitrosoethanes and phosphorus(III) chlorides have provided the phosphoryl chlorides (3) and (4) whilst the same procedure... 

JO Sulfur and Selenium Containing Compounds. - The interaction of 0,0-dialkyl methylphosphonothioates acid with POCI3 to give the chloridates (286) and alkyl phosphorodichloridates parallels reactions of thiophosphoric esters already encountered. The use of Lawesson s reagent to replace the phosphoryl bond in (l,l-difluoroalkyl)phosphonic esters by thiophosphoryl, has been noted (see also reference 258). - ... 

The introduction, removal and modification of substituents on the azetidinone nucleus has received some attention in addition to that mentioned earlier. Chemoselective phosphorylation of the 3-acylamino-azetidinone anion (29) has been achieved with alkyl phosphorodichloridate at low temperature. The diesters (30) were... 

The preparation of furyl phosphorodichloridate is based upon a method to prepare 2-chlorofuran (161 yield, Hormi, Nasman unpublished). Later the preparation was extended to a general method to prepare furyl esters from carboxylic acid chlorides lacking a-hydrogens and alkyl furyl carbonates from primary (other than methyl) and secondary alkyl chloroformates. Phosphoryl chloride was the only acid chloride except carbon analogues found to give a furyl ester by the amine-catalyzed reaction. 

Although the phosphorochloridic acids are, in principle, related as in (5.263), they are more difficult to isolate than their fluoro analogues. Phosphorodichloridic acid can be prepared by the hydrolysis of pyrophosphoryl chloride at -60°C (5.279) or from phosphoryl chloride and water (5.280). It is a clear liquid, stable in the absence of air and has a melting point of -18°C. 

I, 2-0-Isopropylidene-a-D-xylo- and -ribo-furanose each gave the two possible isomers of the corresponding cyclic 3,5-(phenyl phosphate) when treated with phenyl phosphorodichloridate, but only one isomer was formed on phosphorylation of the former compound with bis-(2,2,2-trichloroethyl) phosphorochlori-date. The synthesis of a new type of branched-chain sugar phosphate, trans-3-C-cyanomethylene-3-deoxy-l,2-0-isopropylidene-a-D-erythro-pentofuranose 5-[bis-(2,2,2-trichloroethyl) phosphate], was also reported. 2,3,4,6-Tetra-0-acetyl(or benzoyl)-P-D-glucopyranose reacted with tris(dimethylamino)phosphine and carbon tetrachloride to give both anomeric oxyphosphonium chlorides (see Vol. 9, p. 48), which afforded 1,2-orthoesters with alcohols or a mixture of phenyl 1-thio-D-glucopyranosides with thiophenol. Similar treatment of 2,3,4,6-tetra-... 

Phosphate Activator. MST was shown to be an effective catalyst for the phosphorylation of a 5 -protected mononucleoside. MST was stirred with /t-chlorophenyl phosphorodichloridate and triethylamine and the resulting agent was used directly for the phosphorylation of 5 -protected nucleosides in 70-85% yields. 

Reagent (1) is superior in terms of yield to a variety of phospho-rochloridates, including Phosphorus Oxychloride. For example, in the case of 2-pyridyl aldoxime, with (1) a yield of 52% was obtained, whereas with phosphorus oxychloride the yield was 33% and with phenyl phosphorodichloridate the yield was 47%. The reaction is thought to proceed via an intermediate formed by O-phosphorylation of the aldoxime. The use of spin-labeled versions of (1) has been explored, in which the phenyl is replaced with the 2,2,6,6-tetramethylpiperidyl A -oxide group. ... 

---