Nucleotides nucleosides, protecte

High Pressure Liquid Chromatography.—Reverse phase h.p.l.c. using octadecyl bonded groups has been developed for the rapid and efficient separation of nucleosides, nucleotides, and protected oligonucleotides on both analytical and preparative scales. ... 

Nucleotides from protected nucleosides s. lA, 149 s. a. J. Smrt and F. Sorm, Coll. Czech. Chem. Communs. 25, 553 (1960)... 

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... 

By using a phosphoric diester monotetrazolide, made in situ from the corresponding phosphoric chloride and tetrazole in the presence of triethylamine, die 3 -OH of a suitably protected nucleoside could be phosphorylated to give a fully protected nucleotide [241... 

Product distributions obtained on esterification of nucleosides and nucleotides under basic conditions throw further light on factors affecting selective reactivity. p-Toluenesulfonylation of adenosine 5 -monophosphate in aqueous alkali yielded exclusively (in 54-61% yield) the 2 -p-toluenesulfonate.107 Lack of reaction at HO-3 was attributed either to formation of a phosphoric p-toluenesulfonic anhydride, which sterically protected this hydroxyl group, or to the higher acidity of HO-2. It has been shown that the acidic site (with pKa 12.5) in adenosine is associated with the presence of both HO-2 and HO-3, as replacement of either of these by hydrogen, or of HO-2 by methoxyl, results in loss of this acidity.108 Inductive effects, or the sta-... 

The intermediate phosphite employed in this synthesis was prepared by condensation of duly protected sialic acid with the nucleosidyl phospho-roamidite in the presence of N-PhIMT. Oxidation by TBHP and deprotection according to standard procedures gave the cytidine-S -monophospho-iST-ace-tylneuraminic acid. This synthetic route is claimed to have advantages over procedures published earlier [26]. The same group demonstrated the importance of 3 A and 4 A molecular sieves as moisture scavengers in the reaction of nucleoside phosphoroamidite with a nucleotide. This approach should be likely to find application in the synthesis of biophosphates outside nucleotide chemistry. 

S Additional information <2, 4> (<4> formation of a ternary complex, addition of substrates is random [5] <2> ATP-mediated induced-fit of LID in CMPKcoli modulated by CMP leading to a closed conformation of the active site, protected from water [15] <4> the UMP-CMP kinase has a relaxed enantiospecificity for the nucleoside monophosphate acceptor site, but it is restricted to D-nucleotides at the donor site [26]) [5, 15, 26]... 

The introduction of methoxy substituents increases the ease of removal of trityl groups under acid conditions, but also decreases the selectivity for the primary hydroxyl group [377]. As a compromise, the monomethoxytrityl and dimethoxy-trityl groups found widespread use for the protection of primary positions of glycosides (see, e.g. Ref. [378]) and, especially for the OH-5 function of nucleosides [377]. The use of 6-nitroquinoline instead of pyridine was described [379] to improve the selectivity of monomethoxytritylation of nucleosides and nucleotides bearing free amino groups. A general and rapid procedure was developed for the preparation and isolation of 5 -0-dimethoxy trityl derivatives [380]. 

Lindner J, Grotemeyer J, Schlag EW (1990). Applications of multiphoton ionization mass spectrometry Small protected nucleosides and nucleotides. Int J Mass Spectrom Ion Proc 100 267-285. 

New Protecting Groups in Nucleoside and Nucleotide Chemistry. Pfleide-rer, W. Schirmeister, H. Reiner, T. Pfister, M. Charubala, R. In Biophosphates and their Analogues—Synthesis, Structure, Metabolism and Activity Bruzik, K. S Stec, W. J., Eds. Elsevier Amsterdam, 1987, pp 133-142. 

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