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Title:
METHOD FOR SYNTHESIZING RIBONUCLEIC ACID H-PHOSPHONATE MONOMER, AND OLIGONUCLEOTIDE SYNTHESIS IN WHICH SAID MONOMER IS USED
Document Type and Number:
WIPO Patent Application WO/2017/221929
Kind Code:
A1
Abstract:
The present invention pertains to a method for synthesizing a ribonucleic acid H-phosphonate monomer, and a method for performing oligonucleotide synthesis in which said monomer is used. The present invention pertains to a method for manufacturing an inexpensively manufacturable H-phosphonate nucleoside derivative in which selective protection is provided to position 2' of a ribonucleoside monomer required in RNA oligonucleotide synthesis. The present invention is characterized in that: hydroxyl groups in position 2' and position 3', which have slightly different reactivity, are caused to react with an aromatic acyl halide at low temperature to selectively esterify position 2'; and subsequently the hydroxyl group at position 3' in one pot is captured by a phosphityl group to prevent position 2' and position 3' transfer of the acyl group.

Inventors:
INOUE SATOSHI (JP)
HIMENO KOHEI (JP)
NANKAI HIROKAZU (JP)
TANAKA MUTSUO (JP)
MURAKAMI TEIICHI (JP)
Application Number:
JP2017/022691
Publication Date:
December 28, 2017
Filing Date:
June 20, 2017
Export Citation:
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Assignee:
GENEDESIGN INC (JP)
AIST (JP)
International Classes:
C07H19/10; C07F9/141; C07H19/20; C12N15/09
Domestic Patent References:
WO2011003025A12011-01-06
WO2011028218A12011-03-10
WO2013019874A12013-02-07
WO2012017434A22012-02-09
WO2011133871A22011-10-27
WO2006063717A22006-06-22
WO2014017615A12014-01-30
Foreign References:
JP2010527957A2010-08-19
JP2013527128A2013-06-27
JP2010514768A2010-05-06
JP2005524662A2005-08-18
Other References:
ROZNERS ERIKS ET AL.: "Synthesis of RNA fragments using the H-phosphonate method and 2'-(2-chlorobenzoyl) protection", NUCLEOSIDES & NUCLEOTIDES, vol. 14, no. 3-5, pages 855 - 857, XP008175985
ROZNERS ERIKS ET AL.: "Oligoribonucleotide analogues containing a mixed backbone of phosphodiester and formacetal internucleoside linkages, together with vicinal 2'-O-methyl groups", CHEMBIOCHEM, vol. 8, no. 5, 2007, pages 537 - 545, XP055446429
ROZNERS ERIKS ET AL.: "Synthesis and properties of oligoribonucleotide analogs having amide (3'- CH 2-CO-NH-5') internucleoside linkages", NUCLEOSIDES & NUCLEOTIDES, vol. 16, no. 7-9, 1997, pages 967 - 970, XP055446432
ROZNERS ERIKS ET AL.: "Synthesis and Properties of Oligoribonucleotide Analogs Having Formacetal Internucleoside Linkages", JOURNAL OF ORGANIC CHEMISTRY, vol. 62, no. 6, 1997, pages 1846 - 1850, XP055446433
ROZNERS ERIKS ET AL.: "Solid-phase synthesis of oligoribonucleotides by the H-phosphonate method using 2'-O-benzoyl protective group", BIOORGANICHESKAYA KHIMIYA, vol. 14, no. 11, 1988, pages 1580 - 1582, XP008175978
NEILANDS OJARS ET AL.: "Synthesis of Novel Tetrathiafulvalene System Containing Redox- Active Ribonucleoside and Oligoribonucleotide", ORGANIC LETTERS, vol. 1, no. 13, 1999, pages 2065 - 2067, XP055183187
NEILANDS OJARS: "Dioxo-and aminooxopyrimido- fused tetrathiafulvalenes - base compounds for novel organic semiconductors and for design of sensors for recognition of nucleic acid components", MOLECULAR CRYSTALS AND LIQUID CRYSTALS SCIENCE AND TECHNOLOGY, SECTION A: MOLECULAR CRYSTALS AND LIQUID CRYSTALS, vol. 355, no. 1, 2001, pages 331 - 349, XP055446434
GREENE THEODORA W., WUTS PETER G. M.: "The Role of Protective Groups in Organic Synthesis", PROTECTIVE GROUPS IN ORGANIC SYNTHESIS, 2 October 1998 (1998-10-02), New York, USA, pages 1 - 16, XP009514220, ISBN: 0471220574, DOI: 10.1002/0471220574.ch1
See also references of EP 3473637A4
Attorney, Agent or Firm:
YAMAMOTO Shusaku et al. (JP)
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