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The And Pka Values Of Nucleobases

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NUCLEOSIDE TAUTOMERISM AND pKa VALUES
The nucleophilicity of nucleobases (Figure 2.1.1) is dictated by the pKa of the amino and amido functions and their tautomeric forms. Table 2.1.1 lists the pKa values of nucleobases. The amide-like nitrogens (N3 of uridine and N1 of guanosine) are acidic in character, whereas the ring nitrogens are basic. Therefore, at strongly alkaline pH, the proton at N3 of uridine and thymidine and that at N1 of guanosine are removed. Under acidic conditions (at pH ~3), the sites of protonation are N1 of adenosine and N3 of cytidine. At more acidic pH, the N7 of guanosine and adenosine and the O4 of uridine are protonated. Thus, all the bases remain mostly uncharged in the physiological range of pH 5 to 9 …show more content…

Quite clearly, protecting groups and the protocols for their installation and removal should be designed to avoid various side reactions.
Nucleobases undergo substitution reactions with electrophilic reagents. For example, both N- and O-alkylation of the imide and lactam groups occur with alkylating agents. The N7 position of purines is also a potential site for electrophilic attack (Figure 2.1.5). Because of these competing reactions, simple alkylation of exocyclic amino function is not a viable protection strategy for nucleobases. On the other hand, it is possible to chemoselectively acylate the exocyclic amino group. Thus, acyl-type protecting groups are widely used for the protection of the exocyclic amino groups of nucleosides (Figure 2.1.7).
The imide/lactam NH of thymidine, uridine (pKa, 9.38), and guanosine (pKa, 9.42) is weakly acidic and can deprotonate under basic conditions. The resulting nucleophilic anion can react with a variety of reagents such as activated phosphates, dicyclohexylcarbodiimide (DCC), mesitylene sulfonyl chloride, 1-(mesitylene-2-sulfonyl)-3-nitro-1,2,4-triazole (MSNT), acid chlorides, phosphitylating reagents, and electrophilic reagents that are employed during coupling reactions. These side reactions result in nucleobase-derived N- and O-products.
Nucleosides also react with a variety of nucleophilic reagents. For example,

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