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Non-protected Synthesis of Oligonucleotides

  • Akihiro Ohkubo
  • Kohji Seio
  • Mitsuo Sekine
Chapter

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.

Keywords

N-unprotected DNA and RNA synthesis O-selective phosphorylation Modified oligonucleotides P–N bond cleavage Solid-phase synthesis Silyl type linker 

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Akihiro Ohkubo
    • 1
  • Kohji Seio
    • 1
  • Mitsuo Sekine
    • 2
  1. 1.Department of Life Science and TechnologyTokyo Institute of TechnologyMidoriku, YokohamaJapan
  2. 2.Tokyo Institute of TechnologyYokohamaJapan

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