Oligonucidide Synthesis Essay

1630 Words 7 Pages
Under oxidative conditions, certain nucleobases (for example, adenine and cytosine) can form N-oxides. Also, the C8 position of guanosine is vulnerable to hydrolytic attack under either strongly acidic or strongly alkaline conditions. The 5,6 double bond of pyrimidine nucleosides also reacts with halogens and halohydrins to give the corresponding addition products (Shabarova and Bogdanov, 1994). Selected examples of the side reactions that occur during oligonucleotide synthesis are given below.
Tri-O-acetyluridine (S.1) reacts with MSNT to produce the triazolo derivative S.2 (Figure 2.1.2; Reese and Ubasawa, 1980). During deprotection with ammonium hydroxide, S.2 gives cytidine (S.3). Interestingly, during deprotection with either the tetramethylguanidinium
…show more content…
(1) They can be installed by peracylation of the nucleoside followed by chemoselective O-deacylation (Schaller et al., 1963 ; Rigoli et al., 2009). (2) “Transient” protection approach (Ti et al., 1982) has been widely used. In this procedure, the nucleoside is persilylated using a silylating agent, and the acyl function is installed on the amino group using the corresponding acid chloride or acid anhydride. (3) Some acyl functions such as benzoyl, α-phenylcinnamoyl, and naphthaloyl are directly incorporated on the nucleobase using the corresponding anhydride (Watanabe and Fox, 1966; Bhat et al., 1989). Zhu et al. (2003) reported an improved synthesis of N-benzoylated nucleosides by reducing the amounts of chlorotrimethylsilane (TMSCl) and benzoyl chloride to nearly equivalent quantities. The major advantage of this method is the easier work-up and higher yields. The original method by Ti et al. (1982) was further simplified by eliminating the addition of ammonium hydroxide. (4) The exocyclic amino group of cytidine and deoxycytidine were directly acylated using activated esters (Igolen and Morin, 1980), acid chlorides (Mishra and Misra, 1986, and references therein), or alkyloxycarbonylbenzotriazoles (Himmelsbach et al., 1984). (5) Site-selective incorporation and removal of N-acyl protecting groups have also been achieved by enzymatic methods (Prasad and Wengel, 1996). (6) Selective acylation of …show more content…
For example, (1) N-acetylcytidine was prepared in quantitative yields in 40–60 s by microwave-assisted synthesis (Nahar et al., 1997) (2) N-protected deoxyribonucleosides have also been prepared by microwave-assisted synthesis (Rao et al., 2002). (3) Exocyclic amino groups of adenine and cytosine as benzyloxy carbonyl were protected by reacting with benzyl chloroformate under microwave irradiation (Azzena et al.,

Related Documents