Uridine, synthesis

Basing your answer on reactions that you have seen before, propose a likely mechanism for the condensation reaction in the first step of the preceding uridine synthesis. 

Hydroxymethethyl NAD analog, 74 5-Hydroxymethyl-2, 3 -0-isopropylidene-uridine, synthesis of, 347,348... 

A. Rosenthal and R.H. Dodd, Synthesis of 6-substituted uridines. Synthesis of (R or 5)-6-(3-amino-2-... 

The protected nucleoside-3-phosphoramidite monomer units such as 671 are used in the solid-phase oligonucleotide synthesis. In the 60mer synthesis, 104 allylic protective groups are removed in almost 100% overall yield by the single Pd-catalyze reaction with formic acid and BuNH2[432], N,(9-protection of uridine derivatives was carried out under pha.se-transfer conditions[433]. 

Uric acid, 9-methyl-2,8-dithio-, 5, 590 Uric acid, 9-phenyl-synthesis, 5, 577 Uric acid, 8-thio-synthesis, 5, 577, 582 Uric acid, 1,3,7-trimethyl-ethylation, 5, 534 methylation, 5, 535 Uric acid, 1,7,9-trimethyl-methylation, 5, 535 Uridine... 

Shaw synthesis, 3, 109 Uridine, 2 -deoxy-5-iodo-as pharmaeeutical, 1, 160 Uridine 5 -monophosphate biosynthesis, 1, 88 Uridylic acids occurrence, 3, 142 Urispas... 

By comparing the dissociation constant of 6-azauracil and 6-aza-uridine with those or uracil and uridine, 6-azauridine is now considered to be 1-ribofuranosyl derivative (2-ribofuranosyl-3,5-dioxo-2,3,4,5-tetrahydro-l,2,4-triazine), The same was shown more exactly by comparing the UV and IR spectra and the dissociation constants of 6-azauridine with the two monomethyl derivatives of 6-aza-uracil," Enzymatic synthesis thus, proceeds, in the same way in natural bases and in their aza analogs. 

The breakdown of glycogen to glucose 1-phosphate is catalyzed by phosphorylase. Glycogen synthesis involves a different pathway via uridine diphosphate glucose and glycogen synthase (Figure 18-1). 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

Figure 36-4. Illustration of the tight correlation between the presence of RNA polymerase II and RNA synthesis. A number of genes are activated when Chirono-mus tentans larvae are subjected to heat shock (39 °C for 30 minutes). A Distribution of RNA polymerase II (also called type B) in isolated chromosome IV from the salivary gland (at arrows). The enzyme was detected by immunofluorescence using an antibody directed against the polymerase. The 5C and BR3 are specific bands of chromosome IV, and the arrows indicate puffs. B Autoradiogram of a chromosome IV that was incubated in H-uridine to label the RNA. Note the correspondence of the immunofluorescence and presence of the radioactive RNA (black dots). Bar = 7 pm. (Reproduced, with permission, from Sass H RNA polymerase B in polytene chromosomes. Cell 1982 28 274. Copyright 1982 by the Massachusetts Institute of Technology.)...

Kenner, G.W., Todd, A.R., Weymouth, F.J. (1952) Nucleotides. Part XVII. N-Chloroamides as Reagents for the Chlorination of Diesters of Phosphorous Acid. A New Synthesis of Uridine-5 Pyrophosphate. Journal of the Chemical Society, 3675-3681. 

In ref. [178] other tri(azolyl)phosphines are used for the synthesis of uridine-, adenosine-, and cytidine-oligoribonucleotides according to this method, with azolyl groups... 

The thermal synthesis of nucleoside-5 -phosphite monoester using (NH HPCb was carried out under relatively mild conditions (60°C, reaction time about 24 h) by A. W. Schwartz s group in Nijmegen, Holland in the case of uridine, the yield was 20%. Ammonium phosphate, however, cannot be used it gave yields of only 0.15% after very long reaction times (46 days). This confirms earlier suggestions that nucleoside-H-phosphonates, and condensation products possibly derived from them, would have been formed more readily on the primeval Earth than nucleotides (de Graaf and Schwartz, 2005). 

A convenient synthesis of uridine 2, 3 -cyclic phosphite 15 (as a 3 4 mixture of diasteroisomers because of the chirality at phosphorus) was based on the reaction of the suitably protected uridine derivative 14 with ethyl dichlorophosphite carried out in the presence of triethylamine and anhydrous ethanol (Scheme 6) [21]. After adding ethanol into the reaction medium, an efficient chromatographic separation of the crude reaction product was achieved on silica gel with diethyl ether giving analytically pure phosphite 15 in 75% yield. It is interesting to note that without adding ethanol, 15 is very unstable. 

An alternative approach for the synthesis of 2, 3 -0,0-cyclic //-phosphonate 20a was based on the condensation of a mixture of uridine 3 - and 2 -//-phosphonates (23 and 24 respectively) induced by pivaloyl chloride (Scheme 9) [24], Its reaction with elemental sulfur in carbon disulfide gave 5 -0-DMT-uridine 2, 3 -cyclic phosphorothioate (21a) which after final deprotection afforded the desired 2, 3 -cyclic phosphorothioate 22a (Scheme 9). Its Sp and Rp diastereomers were separated by HPLC [24],... 

In this context, it is interesting to note that the first synthesis of 2, 3 -0,0-cyclic phosphorothioate 22a was reported by Eckstein in 1968 [25], He also isolated pure Rp diastereomer by fractional crystallization of the triethylammonium salts [26] and used it as reference to determine the absolute configurations of the other phosphorothioate analogues [27], 2, 3 -0,0-Cyclic H-phosphonate 20a was used as a key substrate for the synthesis of uridine 2, 3 -0,0-cyclic boranophosphate 27. Silylation of H-phosphate 20a gave the phosphite triester 25 (two diastereomers). Its boronation, with simultaneous removal of the trimethylsilyl group, was achieved by its reaction with borane-A.A-diisopropylethylamine complex (DIPEA-BH3). 

---