Thymidine 3 : 5-cyclic phosphate

The structures of 1,3,2-dioxaphosphinanes of biochemical significance to have been solved by x-ray crystallography are numerous the phenyl ester of thymidine 3, 5 -cyclic phosphate is an example <75PNA(72)1335, 87JA4058>. In the 1,3,5-dioxaphosphinane series, conformational studies by NMR have been supported by x-ray crystal structures <87IZV418>. 

Abbreviations used NAD+ = nicotinamide adenine dinucleotide NADH e reduced nicotinamide adenine dinucleotide NADP = nicotinamide adenine dinudeotide phosphate NAD PH reduced nicotinamide adenine dinucleotide phosphate NMN, NMN+ nicotinamide mononucleotide NMNH2 = reduced nicotinamide mononucleotide a-NAD a-nicotinamide adenine dinucleotide AMP = 5 -adenylic acid 3,5 -AMP adenosine 3, 5 -cycIic phosphate 3 ,5 -UMP = uridine 3, 5 -cyclic phosphate 3, 5 -CMP cytidine 3, 5-cyclic phosphate 3 f5 GMP = guanosine 3 5f-cyclic phosphate 3, 5 TMP thymidine 3, 5 -cyclic phosphate Dibutyryl-3, 5 -AMP = N6,02-dibutyryladenosine 3, 5 -cyclic phosphate 2, 3 -UMP = uridine 2 ,3 -cyclic monophosphate 2, 3 -CMP cytidine 2, 3 -cyclic monophosphate 2, 3 -AMP = adenosine 2, 3 -cyclic monophosphate 2 ,3 -GMP = guanosine 2 3 -cyclic monophosphate 2 -UMP = uridine 2 -phosphate -UMP uridine -phosphate 5 -UMP = uridine 5 phosphate Poly U polyuridylic acid ADP = adenosine 5 -diphosphate FAD = flavin adenine dinucleotide UpA, UpU, ApU and ApA x dinucleoside phosphates of uridine and/or adenine. c See original references for experimental conditions and additional data. 

Since it is well established that the P-chiral phosphorothio-ates serve as effective probes in mechanistic studies for the phos-phoryl group transfer enzymes /16/, we turned our attention to the application of diastereomeric 8 (B=Thy, Ar=pN02C6Hi -,/17f) to elucidate the mode of action of spleen phosphodiesterase (SPDE, EC 3.1.1. 18). This enzyme splits the phosphodiester bonds to yield nucleoside 3 -phosphates. In the case of it was expected that its SPDE-catalyzed hydrolysis in 180 H 2O medium leads to P-chiral thymidine 3 - 180 phosphorothioate. On the contrary to our expectation the main product of this reaction was thymidine cyclic 3 ,5 - Rp phosphorothioate (10) /6/. By treatment of 8 under the same conditions, but in the absence of the enzyme, no trace of J 0 was detected. ... 

A detailed investigation has been reported into the cleavage of 3 - 5 -uridyluridine to form the 2, 3 -cyclic phosphate, and its isomerization to 2 5 -uridyluridine. The hydrolysis of uridine 2 -, 3 - and 5 -phosphoromonothio-ates under acidic and neutral conditions has been investigated in mild acid only hydrolysis to uridine occurs, whilst at low pH desulfurization occurs in the cases of the 2 - and 3 -thioates. The same workers have also studied the kinetics of hydrolysis and desulfurization of the diastereomeric monothio-analogues of uridine 2, 3 -cyclic phosphate under neutral or acidic conditions desulfurization competes with phosphoester hydrolysis. The hydrolysis of the 2 -thionucleoside 3 -phosphate 267 (X=SH) has been studied the predominant reaction pathway at pH 13 is the formation of the 5-phosphate whilst at pH 7-10 mostly the 2, 3 -cyclic monothiophosphate was produced. The 2 -fluorocompound 267 (X=F), which has a C-3 -endo- conformation, underwent hydrolysis ten times faster than did the deoxycompound 267 PC=H). The kinetics of hydrolysis of thymidine 5 -boranomonophosphate (269) have been studied by NMR. It was found that 269 hydrolyses slowly to thymidine and [03P-BH3 ], with the latter hydrolysing even more slowly to phosphonate and boric acid. ... 

In connection with mechanisms for the alkaline hydrolysis of DNA, the kinetics of hydrolysis of thymidine 3 -phosphodiesters with alcohols such as 2,2,2-trichloroethanol, and also of thymidinyl-(3 -5 )-thymidine, have been studied. With the trifluoroethyl phosphate, the 3, 5 -cyclic phosphate is an intermediate in alkaline hydrolysis, but this was not the case with the dinucleotide. Studies using density functional theory calculations were also reported. ... 

Thymidine cyclic 3, 5 -(hydrogen phosphate), 9C1. Cyclic 3, 5 -thymidylic acid [6453-60-7]... 

Thymidine cyclic 3, 5 -(methylphosphate), C-165 Thymidine diphosphate, T-105 Thymidine 3, 5 -diphosphate, T-106 Thymidine 3 -phosphaie, T-107 Thymidine 5 -phosphate, T-108... 

In the area of 3, 5 -cyclic nucleotides, it has been found that attempted 5 -phosphorylation of the 3 -epimers of thymidine and deoxyadenosine with phosphoryl chloride gave the cyclic phosphates 195 (B = Ad, T) the 5 -phosphates could be obtained by phosphorylation of the 3 -0-benzoyl derivatives.245 Two groups have reported the synthesis of base-modified derivatives of c AMP (e.g. benzimidazoles, benzotriazoles, indazoles), for evaluation as activators of cAMP-dependcnt protein kinase 1.246,247 There have been syntheses described of ribonucleoside 3 ,5 -cyclic methyl- and phenyl-phosphonates248,249 and -phosphonothioates, one of the procedures giving both the cyclic phosphonates and phosphonothioates as the 5p-epimer only.249 a paper... 

Bentrude, W G., Sopchik, A, E, and Gajda. T. (1989) Stereo-and regio-chem-istries of the oxidations of 2-methoxy-5-t rr-butyl-l,3,2-dioxaphosphorinanes and the cyclic methyl 3, 5 -phosphite of thymidine by H2O/I2 and O2/AIBN to P-chiral phosphates. NMR assigment of phosphorus configuration to the diastereomeric thymidine cyclic methyl 3, 5 -monophosphates. J, Am, Chem. Soc, 111,3981-3987... 

Both the 5 -methyl ester of pdT and thymidine 5 -fluorophosphate are poor substrates. The products are methylphosphate and fluorophosphate plus dT. When PNP-pdTp-PNP is used as a substrate, there is a rapid release of PNP-phosphate from the 5 position along with a slow release of PNP from the 3 position (18). Other substrates with a 3 -PNP consistently give rise to some PNP as a product. This secondary activity of SNase is poorly understood. 2, 3 -Cyclic phosphate esters are not substrates for SNase (5). 

The non-specific tritiation of papaverine ha been described,13 as have methods for the detection of the alkaloid in body fluids.1415 The effects of papaverine on the biochemical fate of thymidine phosphate in the thymus,16 on cyclic AMP and the uptake of calcium in isolated pig auricle,17 on the monosynaptic reflex,18 on the L-DOPA-influenced secretion of GH and PRL,19 on cerebral blood flow,20 and on longitudinal smooth muscle21 have been studied, as have the /3-receptor-stimulant... 

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