Nucleotides oligonucleotide syntheses protection

A supported sulfide source has been demonstrated by Zhang et al.16 to synthesize oligonucleotide phosphorothioates (entry 12). Aminodithiazole-thione attached to a methacrylate-ethyleneglycol copolymer is used to efficiently convert a nucleotide phosphite to a phosphorothioate. The product nucleotide possesses protecting groups suitable for solid-phase oligonucleotide synthesis and thus is a valuable building block for nucleic acid therapeutics. 

Nucleotides and nucleic acids, N-NMR study of 83ACR35. Oligonucleotide synthesis using protecting groups 82YGK1159 ... 

This group was developed for 5 -hydroxyl protection in oligonucleotide synthesis. It is stable to the conditions for nucleotide coupling using the phosphoramidite approach. It is not stable to acid or to 12/pyridine/THF, conditions used for phosphite oxidation. It has been used to prepare a 20-mer. ... 

This group was developed as an oxidatively cleavable group for 5-protection in oligonucleotide synthesis. It is prepared either from the carhonylimidozolide or the 4-nitrophenyl carbonate. Alternatively the alcohol to be protected can be treated with carbonyl diimidazole followed by sulfenyl protected diol. Yields range from 70% to 93%. The MTFOC group is cleaved upon oxidation with I2, which releases the alcohol that in the presence of pyridine cyclizes to form a carbonate with release of the nucleotide. The oxidation step is fast (<1 min), and the cyclization to form the carbonate has a half-life of 51 min. ... 

S. An efficient synthesis of enantiomeric ribonucleic acids from D-glucose. Helv. Chim. Acta 1997, SO 2286—2314). The protected enantiomeric cytidine was produced in 94% yield by the above reaction. After adjusting protecting groups, solid-phase oligonucleotide synthesis methods (Section 25.7) were used with this compound and the other three nucleotide monomers (also derived from L-ribose) for preparation of the unnatural RNA enantiomer. See also Vorbriiggen, H. Ruh-Pohlenz, C., Handbook of Nucleoside SynlhestsTy Wiley Hoboken, NJ, 2001. 

The problems of laboratory DNA synthesis are similar to, but even greater than, those of peptide synthesis, mainly because nucleotides have more complicated structures than do amino acids. Each nucleotide has several functional groups that must be protected, and later deprotected, during synthesis. Despite these difficult chemical problems, methods for oligonucleotide synthesis have been developed in various laboratories. Using these methods, Khorana and coworkers were able to synthesize a gene for the first time, by a combination of chemical and enzymatic means. 

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