Adenosine, synthesis

Lesnik, E.A. et al, Oligodeoxynucleotides containing 2 -0-modified adenosine synthesis and effects on stability of DNA RNA duplexes. Biochemistry, 32,7832,1993. 

CycHc adenosine monophosphate (cAMP), produced from ATP, is involved in a large number of ceUular reactions including glycogenolysis, Hpolysis, active transport of amino acids, and synthesis of protein (40). Inorganic phosphate ions are involved in controlling the pH of blood (41). The principal anion of interceUular fluid is HP (Pig. 3) (41). 

DiaZepin Nucleosides. Four naturally occurring dia2epin nucleosides, coformycin (58), 2 -deoxycoformycin (59), adechlorin or 2 -chloro-2 -deoxycoformycin (60), and adecypenol (61), have been isolated (1—4,174,175). The biosynthesis of (59) and (60) have been reported to proceed from adenosine and C-1 of D-ribose (30,176,177). They are strong inhibitors of adenosine deaminase and AMP deaminase (178). Compound (58) protects adenosine and formycin (12) from deamination by adenosine deaminase. Advanced hairy cell leukemia has shown rapid response to (59) with or without a-or P-interferon treatment (179—187). In addition, (59) affects interleukin-2 production, receptor expression on human T-ceUs, DNA repair synthesis, immunosuppression, natural killer cell activity, and cytokine production (188—194). 

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasaHy with vesicular stomatitis vims ( 5)-DHPA significantly increased survival from the infection. (5)-DHPA did not significantly reduce DNA, RNA, or protein synthesis and is not a substrate for adenosine deaminase of either bacterial or mammalian origin. However, (5)-DHPA strongly inhibits deamination of adenosine and ara-A by adenosine deaminase. Its mode of action may be inhibition of Vadenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of Vadenosylmethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block vims repHcation by interference with viral mRNA methylation. 

Adenosine is not active orally, but adrninistered as an iv bolus dmg adenosine rapidly eliminates supraventricular tachycardias within 1—2 min after dosing. The dmg slows conduction through the AV node. Adenosine is rapidly removed from the circulation by uptake into red blood ceUs and vascular endothehal ceUs. Thus the plasma half-life is less than 10 s. Adenosine is rapidly metabolized to inosine or adenosine monophosphate and becomes part of the body pool for synthesis of adenosine-triphosphate. 

Adenosine, N -dimethyI-5 -0-methyI-2, 3 -0-isopropylidene-methylation, 5, 537 Adenosine, homocitrullyamino-biological activity, 5, 603 Adenosine, 1-isopentenyI-synthesis, 5, 594 Adenosine, 2 -0-methyI-occurrence, 5, 600 Adenosine, 2-phenyIamino-synthesis, 5, 590 Adenosine, 2, 3, 5 -tri-0-acetyl bromination, 5, 540 Adenosine-8-earboxylic acids synthesis, 5, 593 Adenosines, isopropylidene-synthesis, 5, 584... 

The consequence of ADA deficiency is accumulation of adenosine and 2 -deoxyadenosine, substances toxic to lymphocytes, important cells in the immune response. 2 -Deoxyadenosine is particularly toxic because its presence leads to accumulation of its nucleotide form, dATP, an essential substrate in DNA synthesis. Elevated levels of dATP actually block DNA replication and cell division by inhibiting synthesis of the other deoxynncleoside 5 -triphosphates (see Chapter 27). Accumulation of dATP also leads to selective depletion of cellular ATP, robbing cells of energy. Children with ADA SCID fail to develop normal immune responses and are susceptible to fatal infections, unless kept in protective isolation. 

Synthesis of adenosine triphosphate by means of cyclic catalysis (Nobel lecture) 98AG(E)2308. 

Figure 29.1 An overview of catabolic pathways for the degradation of food and the production of biochemical energy. The ultimate products of food catabolism are C02 and H2O, with the energy released in the citric acid cycle used to drive the endergonic synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) plus phosphate ion, HOPO32-.

Atorvastatin, structure of, 105. 516 ATP (see Adenosine triphosphate) ATZ, see Anilinothiazolinone, 1031-1032 Aufbau principle. 6 Axial bonds (cyclohexane), 119 drawing, 120 Azide, amines from, 929 reduction of, 929 Azide synthesis, 929 Azo compound, 944 synthesis of, 944-945 uses of. 945... 

Pentostatin (deoxycoformycin Fig. 4) is a purine isolated from cultures of Streptomyces antibioticus. Its mode of action involves inhibition of adenosine deaminase, which plays a key role in purine salvage pathways and DNA synthesis. As a consequence, deoxyadenosine triphosphate (dATP) is accumulated, which is highly toxic to lymphocytes. This is associated with augmented susceptibility to apoptosis, particularly in T cells. 

The organism utilized is a mutant of E. coli blocked in the synthesis of aromatic amino acids before the shikimate step. Cells are first grown in the presence of adenosine, a technique that temporarily derepresses the system of en-... 

Escherichia coli Adenine and adenosine are inhibitory74 and the synthesis of thiamine can be derepressed by culture in their presence.13,75 adth- Mutants are known.76 [l4C]Formate incorporates at C-2 of pyramine without dilution of molar activity. Glycine labeled with stable isotopes was fed to E. coli and the pyramine was analyzed by mass spectrometry. The two carbon atoms of glycine separated during the biosynthesis. The carboxyl was found12 at C-4, and the C-N fragment was the precursor of C-6-N-1. In conclusion, it is beyond doubt that pyramine synthesis follows the AIR pathway in E. coli. 

The Merck compound MK-0608 is a 2 -C-Me-7-deaza-adenosine analog, which has recently been reported to show a 5.7 log drop in viral load in HCV-infected chimpanzees after dosing QD at 2mg/kg (Olsen 2006). An efQcient and practical process for preparing kilogram quantities has been described (Bio et al. 2004). The 12-step synthesis provides an impressive 35% overall yield and starts from the inexpensive diacetone-D-glucose. The synthesis features a novel acyl migration in route to prepare the key crystalline furanose diol intermediate (Fig. 5). The conditions... 

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