Abstract
Much attention has been paid to the development of effective methods for synthesizing modified oligonucleotides that have various functional groups. Recently, we have developed a selective phosphorylation toward the hydroxyl group (O-selective phosphorylation), which is named as the proton-block method. An activated phosphite method was also developed to synthesize modified DNA oligonucleotides having alkaline-labile functional groups. The DNA synthesis using the activated phosphite method, which involves a phosphite intermediate generated from the phosphoramidite building block, presents excellent chemoselectivity toward the hydroxyl groups on resins under solid-phase conditions. In addition, the O-selectivity of the phosphorylation with P–N bond cleavage using 6-nitro-HOBt is more than 99% in the RNA synthesis without base protection. In this review, we summarize the O-selective phosphorylation in DNA and RNA synthesis without base protection and the synthesis of modified oligonucleotides having alkaline-labile functional groups using these new methods.
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Unpublished data
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Ohkubo, A., Seio, K., Sekine, M. (2018). Non-protected Synthesis of Oligonucleotides. In: Obika, S., Sekine, M. (eds) Synthesis of Therapeutic Oligonucleotides. Springer, Singapore. https://doi.org/10.1007/978-981-13-1912-9_1
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DOI: https://doi.org/10.1007/978-981-13-1912-9_1
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