Synthesis of Nucleotides

Methods for the s)mthesis of nucleotides may be divided into four categories (1) phosphorylation of available hydroxyl groups of selectively protected nucleosides with phosphorylating agents, (2) phosphorolysis of activated nucleosides, and (3) condensation of a suitably protected 

Todd and coworkers,has served as an excellent phosphorylating agent, as the benzyl groups are readily removed by catalytic hydrogenation or 

In some cases, dibenzyl phosphorochloridate was not sufficiently active for use as a phosphorylating agent in nucleotide syntheses, as shown, for example, by rather unsuccessful attempts to convert 2, 3 -0-isopropyl-ideneguanosine into its 6 -phosphate.i i Convenient methods had been 

Other reagents of the pyrophosphate type (anhydrides) have been useful in nucleotide synthesis. 0-Benzylphosphorous 0,0-diphenylphosphoric 

A most useful method of phosphorylation of nucleosides was developed by Gilham and Tener. - 2-Cyanoethyl phosphate (64) and an excess of 

---

It is now known that each codon consists of a sequence of three nucleotides ie, it is a triplet code (see Table 38—1). The deciphering of the genetic code depended heavily on the chemical synthesis of nucleotide polymers, particularly triplets in repeated sequence. 

In the phosphite triester approach to the synthesis of nucleotides, morpholinophos-phorous ditetrazolide is used as the phosphitylating agent. The procedure generally consists of three steps ... 

Synthesis of nucleotides and nucleosides, nucleotide coenzymes, polynucleotides, and histidine... 

Bulter, T. and Elling, L. (1999) Enzymatic synthesis of nucleotide sugars. Glycoconjugate Journal, 16, 147-159. 

Capacity to utilise catalytic Ni2+, Fe2+, W(Mo) and Mg2+ in cell metabolism (see Table 5.2). All primitive cells had to reduce CO (C02) before engaging in condensation reactions. We suppose nitrogen was available as NH3 for protein synthesis and HCN for the synthesis of nucleotide bases. 

This review summarizes recent approaches towards the selective formation of anomeric aldose and aldulosonic acid phosphates of biological relevance, in particular as precursors for the synthesis of nucleotide-activated sugars. 

Irradiation of dianisyl alkyl phosphates gives alkyl phosphates and 4,4 -dimethoxy-biphenyl in yields exceeding 90%.6 As stated by the authors, this type of reaction appears to have promise for the synthesis of nucleotides. 

The structure of cobalamin is more complex than that of folic acid (Figure 15.2 and 15.3). At its heart is a porphyrin ring containing the metal ion cobalt at its centre. In catalytic reactions the cobalt ion forms a bond with the one-carbon group, which is then transferred from one compound to another. Vitamin B12 is the prosthetic group of only two enzymes, methylmalonyl-CoAmutase and methionine synthase. The latter enzyme is particularly important, as it is essential for the synthesis of nucleotides which indicates the importance of vitamin B12 in maintenance of good health. 

A. Salvage pathways allow synthesis of nucleotides from free purines or pyrimidines that arise from nucleic acid degradation or dietary sources, which is more economical for the cell than de novo synthesis. 

This selectivity permits use of a methyl protecting group in phosphate triester synthesis of nucleotides. Removal is effected by heating solutions of the protected nucleotide in f-hutylaminc at reflux (46°) for 15 hours. ... 

Two types of pathways lead to nucleotides the de novo pathways and the salvage pathways. De novo synthesis of nucleotides begins with their metabolic precursors amino acids, ribose 5-phosphate, C02, and NH3. Salvage pathways recycle the free bases and nucleosides released from nucleic acid breakdown. Both types of... 

Sulfanilamide and its derivatives competitively inhibit the synthesis of folic acid in micro-orgenisms and, thereby, decrease the synthesis of nucleotides needed for the replication. 

The effects of cobalamin deficiency are most pronounced in rapidy dividing cells, such as the erythropoietic tissue of bone marrow and the mucosal cells of the intestine. Such tissues need both Die N5-N10-methylene and N10-formyl forms of tetrahydrofolate for Ihe synthesis of nucleotides required for DNA replication (see pp. 291, 301). However, in vitamin B12 deficiency, the N5-methyl form of tetrahydrofolate is not efficiently used. Because the methylated fonn cannot be converted directly to other forms of tetrahydrofolate, tie Ns-methyl form accumulates, whereas the levels of the other forms decrease. Thus, cobalamin deficiency is hypothesized to lead to a deficiency of the tetrahydrofolate forms needed in purine and thymine synthesis, resulting in the symptoms of megaloblastic anemia. 

A further step toward the synthesis of nucleotides was taken in 1914, when Fischer succeeded in phosphorylating IV-glucosyltheophylline with phosphoiyl chloride and pyridine. The ciystalline product obtained bore the phosphate group on the glucose portion. 

The equilibria in these phosphoribosyltransferase reactions favor nucleotide synthesis, and since the inorganic pyrophosphate released is rapidly hydrolyzed by inorganic pyrophosphatase, the coupling of these reactions makes the synthesis of nucleotide irreversible. However, the efficiency of salvage is heavily dependent on the intracellular concentration of PRPP. 

---