Nucleic Acid Chemistry

In nucleic acid synthesis, silylation converts insoluble nucleobases into lipophilic trimethylsilyled derivatives, which are readily soluble in organic solvents, permitting homogenous chemical reactions. The trimethylsilylated nucleobases react with protected sugars to afford nucleosides. The procedure is commonly referred to as the Hilbert-Johnson reaction modified by Vorbrüggen et al.
Phosphorylating and phosphorothioating agents, condensing agents and protecting agents for hydroxy and amino groups are of importance in the synthesis of DNA and RNA chains. Active research on chemical synthesis of DNA and RNA is being conducted, and a variety of synthetic methods using these agents are being developed. The dicyclohexylcarbodiimide (DCC) method exemplified by the Khorana group, the phosphotriester method and phosphitetriester method by the team of Letsinger and the phosphoramidite method by the Caruthers group are examples of the various synthetic methods. Recently, the phosphoramidite method has been used frequently in tandem with the penetration of DNA synthesizers, thus 2-cyanoethyl N,N,N',N'-tetraisopropylphosphordiamidite (Product No. C2228) has been the reagent of frequent choice for the phosphitylation due to its ease in handling and safety.^1,2,3) Xanthane hydride (Product No. X0001) is widely used as a sulfur-transfer reagent for synthesis of oligonucleotide phosphorothioates. 1,2,4-Triazole (Product No. T0340) and 1H-tetrazole are also used for chemical conversion of uridines into cytidines.
Chemically synthesized DNA is becoming important as a primer for the PCR method, an antisense molecule, or an element of the DNA computer.

References

• 1) I. Okamoto, K. Shohda, K. Seio, M. Sekine, J. Org. Chem. 2003, 68, 9971.
• 2) A. Misra, S. Mishra, K. Misra, Bioconjugate Chem. 2004, 15, 638.
• 3) R. Gukathasan, M. Massoudipour, I. Gupta, A. Chowdhury, S. Pulst, S. Ratnam, Y. S. Sanghvi, S. A. Laneman, J. Organomet. Chem. 2005, 690, 2603.