Synthesis and Properties of the 5‑Methyluridine Derivative of 3,4-Dihydro‑2H‑pyran-Bridged Nucleic Acid (DpNA)

• Published in: Journal of organic chemistry Vol. 80; no. 21; pp. 10474 - 10481
• Main Authors: Osawa, Takashi, Hari, Yoshiyuki, Dohi, Masakazu, Matsuda, Yuya, Obika, Satoshi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.11.2015; Amer Chemical Soc
• Subjects: Bridged-Ring Compounds - chemical synthesis; Bridged-Ring Compounds - chemistry; Chemistry; Chemistry, Organic; Nucleic Acid Conformation; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Oligonucleotides, Antisense - chemistry; Physical Sciences; Pyrans - chemistry; RNA - chemistry; Science & Technology; Uridine - analogs & derivatives; Uridine - chemical synthesis; Uridine - chemistry; THERAPEUTIC APPLICATIONS; THERMODYNAMIC STABILITIES; DUPLEX STABILITY; ANALOGS; AFFINITY; RING; ENA; ANTISENSE OLIGONUCLEOTIDES; NUCLEOSIDE SYNTHESIS; LNA
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.5b01425

A novel 2′-O,4′-C-bridged nucleic acid, 3,4-dihydro-2H-pyran bridge moiety (DpNA), with a dioxabicyclo[3.2.1]­oct-3-ene ring was designed. Construction of the dihydropyran bridge was achieved by dehydration of a six-membered hemiacetal ring, and the DpNA monomer was synthesized in 10 steps from 5-methyluridine (total yield 9%). The synthesized DpNA monomer was incorporated into oligonucleotides to examine the properties of the modified oligonucleotides. The DpNA-modified oligonucleotides possessed high affinity toward ssRNA and were more resistant to nucleases compared to the corresponding natural oligonucleotide.