Nucleoside hydrolysis

If it is desired to isolate only the pyrimidine nucleosides, hydrolysis of the nucleic acid may be carried out in acid medium.6 This process, however, entails extensive deamination of cytidine to uridine. The pyrimidine... 

Show a mechanism for nucleoside hydrolysis in aqueous acid. 

Purine nucleoside hydrolysis decelerated by bridging with 3, 5 -cyclic phosphate... 

Mild acid hydrolysis of the deaminated purine nucleotides, xanthylic acid and inosinic acid, gives the purine bases (xanthine and hypo-xanthine, respectively) and a reducing sugar phosphate. The same hydrolytic products are obtained by use of a specific pancreatic enzyme. On the other hand, mild alkaline hydrolysis of a nucleotide, or treatment with the appropriate enzyme, liberates free phosphoric acid and a non-reducing compound of base and sugar, known as a nucleoside. (Hydrolysis of ribosenucleic acid with fairly dilute ammonia under pressure, during 3.5 hours at a bath temperature of 175 to 180 , gives an equimolecular mixture of four nucleosides). 

Methylcytosine (964 X = O) was synthesized in 1901 and its isolation from hydrolyzates of tubercule bacilli was reported in 1925. However, this was later shown to be incorrect and only about 1950 was it isolated by hydrolysis of the deoxyribonucleotide fractions from thymus, wheat germ and other sources (50MI21302). Nucleotides and a nucleoside of 5-methylcytosine are known. 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

CF3COOH, r-BuOH, 20°, 2-30 min, then Bio-Rad 1x2 (OH ) resin.These conditions were used to cleave the trityl group from the 5 -hydroxyl of a nucleoside. Bio-Rad resin neutralizes the hydrolysis and minimizes cleavage of,glycosyl bonds. 

These were originally prepared by Khorana as selective protective groups for the 5 -OH of nucleosides and nucleotides. They were designed to be more acid-labile than the trityl group because depurination is often a problem in the acid-catalyzed removal of the trityl group. Introduction of p-methoxy groups increases the rate of hydrolysis by about one order of magnitude for each p-methoxy substituent. For 5 -protected uridine derivatives in 80% AcOH, 20°, the time for hydrolysis was... 

This group was developed for protection of the 5 -OH group in nucleosides. The derivative is prepared from the corresponding triaiylmethyl chloride, and is cleaved by reductive cleavage (Zn/AcOH) of the phenacyl ether to the p-hydroxyphenyl-diphenylmethyl ether followed by acidic hydrolysis with formic acid. ... 

The pixyl ether is prepared from the xanthenyl chloride in 68-87% yield. This group has been used extensively in the protection of the 5 -OH of nucleosides it is readily cleaved by acidic hydrolysis (80% AcOH, 20°, 8-15 min, 100% yield, or 3% trichloroacetic acid). It can be cleaved under neutral conditions with ZnBrj, thus reducing the extent of the often troublesome depurination of A -6-benzyloxy-adenine residues during deprotection. Conditions which remove the pixyl group also partially cleave the THP group (t,/2 for THP at 2 -OH of ribonucleoside = 560 s in 3% Cl2CHC02H/CH2Cl2). ... 

The crotonate esters, prepared to protect a primary hydroxyl group in nucleosides, are cleaved by hydrazi ne (MeOH, Pyr, 2 h). The methoxycrotonate is 100-fold more reactive to hydrazinolysis and 2-fold less reactive to alkaline hydrolysis than the corresponding acetate. ... 

Sulfenamides, R2NSR, prepared from an amine and a sulfenyl halide, " are readily cleaved by acid hydrolysis and have been used in syntheses of peptides, penicillins, and nucleosides. They are also cleaved by nucleophiles, and by Raney nickel desulfurization. ... 

Nucleosides are much more water-soluble than the free bases because of the hydrophilicity of the sugar moiety. Like glycosides (see Chapter 7), nucleosides are relatively stable in alkali. Pyrimidine nucleosides are also resistant to acid hydrolysis, but purine nucleosides are easily hydrolyzed in acid to yield the free base and pentose. 

FIGURE 11.29 The vicinal—OH groups of RNA are susceptible to nucleophilic attack leading to hydrolysis of the phosphodiester bond and fracture of the polynucleotide chain DNA lacks a 2 -OH vicinal to its 3 -0-phosphodiester backbone. Alkaline hydrolysis of RNA results in the formation of a mixture of 2 - and 3 -nucleoside monophosphates. 

DNA is not susceptible to alkaline hydrolysis. On the other hand, RNA is alkali labile and is readily hydrolyzed by dilute sodium hydroxide. Cleavage is random in RNA, and the ultimate products are a mixture of nucleoside 2 - and 3 -monophosphates. These products provide a clue to the reaction mechanism (Figure 11.29). Abstraction of the 2 -OH hydrogen by hydroxyl anion leaves a 2 -0 that carries out a nucleophilic attack on the phosphorus atom of the phosphate moiety, resulting in cleavage of the 5 -phosphodiester bond and formation of a cyclic 2, 3 -phosphate. This cyclic 2, 3 -phosphodiester is unstable and decomposes randomly to either a 2 - or 3 -phosphate ester. DNA has no 2 -OH therefore DNA is alkali stable. 

The furanoid vinyl ethers described above are of interest in view of the structure of the nucleoside antibiotic angustmycin A (2) (15) which also contains an exocyclic double bond. As a first step towards the synthesis of analogs of angustmycin A (2), preparation of exocyclic vinyl ethers from hexulofuranoid derivatives was studied. Benzoylation of 2,3 4,6-di-0-isopropylidene-a-L-ryZo-hexulofuranose (44) followed by selective acid hydrolysis of the 4,6-O-isopropylidene group afforded l-0-benzoyl-2,3-0-isopropylidene-a-L-ryZohexulofuranose (45) in 72%... 

The nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are biological polymers that act as chemical carriers of an organism s genetic information. Enzyme-catalyzed hydrolysis of nucleic acids yields nucleotides, the monomer units from which RNA and DNA are constructed. Further enzyme-catalyzed hydrolysis of the nucleotides yields nucleosides plus phosphate. Nucleosides, in turn, consist of a purine or pyrimidine base linked to Cl of an aldopentose sugar—ribose in RNA and 2-deoxyribose in DNA. The nucleotides are joined by phosphate links between the 5 phosphate of one nucleotide and the 3 hydroxyl on the sugar of another nucleotide. 

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