The cyano-ethoxy carbonyl protection Manoharan et al. (1999) developed 2(cyanoethoxycarbonyloxy)succinimide S.27a a stable, crystalline, and convenient reagent for the protection of pendant akylamines in oligonucleotides (Figure X.X.X). The 2-cyanoethyl (ce) group is the most common phosphate protecting group in oligonucleotides; however, ce and corresponding 2-(cyanoethoxycarbonyl) group were not utilized for the nucleobase protection until 2000. Merk et al. (2000) developed 2-(cyanoethoxy)carbonyl (ceoc) protection for the protection of the excocylic amino group of adenine, guaninine, and cytosine. The (2-cyanoethoxy)carbonylation reactions were carried out with either 2-cyanoethyl carbonochloridate (S.27b ) or 1-((2-cyanoethoxy)carbonyl)-3-methyl-1H -imidazolium chloride (S.27c) (Figure X.X.X), which were synthesized by the
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Nevertheless, it is known that biscarbamate can be removed under midly basic to neutral conditions and is hence suitable N-protecting group for nucleosides (Sikehi et al., 2006 and reference theirin). A solvent-free reaction utilizing a simple low-energy ball mill apparatus was reported to convert the amino groups of nucleosides S.36, adenosine, 2-deoxyadenosine, cytidine, 2-deoxycytidine, guanosine, and 2-deoxyguanosine as well as some of their ribosyl O-protected derivatives, to the corresponding bis-N-Boc carbamates S.37 (Sikehi et al., 2006). For guanosine compounds, the carbonyl group of the base moiety was also protected as its O-Boc enol carbonate (Figure X.X.X). Transient in situ O-silylation facilitated the preparation of bis-N-Boc nucleosides from unprotected sugars. This strategy allows the protection of nucleosides with a base-stable and acid-labile group suitable for the preparation of base-sensitive oligonucleotides as well as for further manipulation. However, the utility of this diBoc carbamate protection is yet to be explored in oligonucleotide
Nevertheless, it is known that biscarbamate can be removed under midly basic to neutral conditions and is hence suitable N-protecting group for nucleosides (Sikehi et al., 2006 and reference theirin). A solvent-free reaction utilizing a simple low-energy ball mill apparatus was reported to convert the amino groups of nucleosides S.36, adenosine, 2-deoxyadenosine, cytidine, 2-deoxycytidine, guanosine, and 2-deoxyguanosine as well as some of their ribosyl O-protected derivatives, to the corresponding bis-N-Boc carbamates S.37 (Sikehi et al., 2006). For guanosine compounds, the carbonyl group of the base moiety was also protected as its O-Boc enol carbonate (Figure X.X.X). Transient in situ O-silylation facilitated the preparation of bis-N-Boc nucleosides from unprotected sugars. This strategy allows the protection of nucleosides with a base-stable and acid-labile group suitable for the preparation of base-sensitive oligonucleotides as well as for further manipulation. However, the utility of this diBoc carbamate protection is yet to be explored in oligonucleotide