Phosphorodichloridates cyclic

A remarkable demonstration of the ease of formation of six-co-ordinate species from four-co-ordinate precursors is the observation that both phenyl phosphorodichloridate and the cyclic ester (33) give the salt (34) when treated... 

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... 

D-glucopyranosyladenine with phenyl phosphorodichloridate (89) (see p. 337) yielded 9-/8-D-glucopyranosyladenine 4 6 -cyclic phosphate. The 2 4 -, 3 6 -, and 4 6 -cyclic phosphates of l-/3-D-glucopyranosyl-uracil have also been reported. ... 

Novel cyclic di- and triphosphate derivatives of 3 -amino-3 -deoxyadenosine-5 -diphosphate (75) and triphosphate (76) have been prepared " by cyclisation of the respective 5 -di- and triphosphate derivatives of 3 -A -Boc-3 -amino-3 -deoxyadenosine using the water-soluble carbodiimide 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), followed by removal of the Boc protecting group with TFA. The acyclic polyphosphate precursors were prepared according to Yoshikawa and Ludwig after first dissolving the nucleoside in hot triethylphosphate. The reaction proceeds via the intermediacy of the 5 -phosphorodichloridate derivative, partial hydrolysis of which gives the monophosphate, whilst traces of pyrophosphoryl chloride result in... 

Cyclic phosphoric acid esters from phosphorodichloridates O... 

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-... 

Compounds possessing the cyclic phosphate structure may be prepared by the action of phosphorus oxychloride or phenyl phosphorodichloridate on a glycol, or by treating phosphate monoesters with trifluoroacetic anhydride (173) or a carbodiimide reagent (f74). The latter is the preferred reagent since it may be used in the presence of water and usually gives a good yield of a pure product. The reaction is formulated as follows ... 

The cyclic product is extremely sensitive to moisture (hydrolysis) and was more readily isolated as the cyclic diester. An interesting correlation has been observed the phenyl triesters of high energy cyclic phosphates (cyclic nucleotides, ethylene phosphate) are very reactive species, susceptible to decomposition. On the other hand, the phenyl triesters of low energy cyclic phosphates are stable, crystalline compounds. Hence, for example, the phenyl triester of trimethylene phosphoric acid is a crystalline compound readily prepared in high yield by reaction of 1,3-propanediol with phenyl phosphorodichloridate. 

Several other compounds are formed in the reaction such as diesters (R0)2P02H, triesters (RO)3PO and cyclic esters. In order to avoid these side reactions, substituted compounds are now used, particularly diphenyl phosphorochloridate [(CjH50)2POCl], dibenzyl phosphorochloridate [(CfiH.CHiOliPOCllformonoesters, and phenyl phosphorodichloridate (C6HjO-POCl2) for diesters. 

Phosphorus oxychloride is very useful in the preparation of nucleoside 5 -phosphates (eq 19) given appropriate mixtures of POCI3, pyridine, and water. The primary hydroxy (5 ) is sufficiently reactive for there to be minimal formation of cyclic phosphates at the 2,3-positions of nucleosides. The intermediate phosphorodichloridate can be converted to the corresponding triphosphate by treatment with inorganie phosphate in a convenient one-pot fashion. 

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