Title:
PRODUCTION OF HIGHLY FAT-SOLUBLE PHOSPHORAMIDITE
Document Type and Number:
WIPO Patent Application WO/2019/131719
Kind Code:
A1
Abstract:
The purpose of the present invention is to provide: a method for purifying and producing a highly fat-soluble phosphoramidite; a capping reaction using said highly fat-soluble phosphoramidite compound; and a method for producing oligonucleotides that comprises a step involving said capping reaction and that is performed by a liquid-phase process using a pseudo-solid phase protecting group. The present invention also provides a method for producing a compound represented by formula (I) (wherein R1, R2, and R3 are as defined in the Description), the production method comprising the following steps: (1) reacting an aliphatic alcohol and a trivalent phosphorus compound in an organic solvent in the presence of an activating agent or an organic base; (2) separating the obtained reaction mixture by using water; (3) collecting the organic layer after said step (2) and concentrating the same (steps (2) and (3) can be omitted in cases where the organic solvent used in said step (1) is a nitrile-based solvent); (4) dissolving the residue obtained in said step (3) in an aliphatic hydrocarbon-based solvent (steps (2) to (4) can be omitted in cases where the organic solvent used in said step (1) is an aliphatic hydrocarbon-based solvent); (5) separating the aliphatic hydrocarbon-based solution prepared in said step (4) by using a nitrile-based solvent; and (6) collecting the aliphatic hydrocarbon-based solution after said step (5) to obtain a phosphoramidite compound as a solution. The present invention also provides: a capping reaction reagent which is a solution containing a highly fat-soluble phosphoramidite compound obtained by said production method, or a composition containing said solution and additives as appropriate; a capping reaction using said capping reaction reagent; and a method for producing (oligo)nucleotides that comprises a step involving said capping reaction and that uses a pseudo-solid phase protecting group.
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Inventors:
FUJIHARA TSUYOSHI (JP)
NAKAMURA KENICHI (JP)
KUROME TORU (JP)
SASAHARA DAISUKE (JP)
SHIMAHARA AKIKO (JP)
NEYA MASAHIRO (JP)
NAKAMURA KENICHI (JP)
KUROME TORU (JP)
SASAHARA DAISUKE (JP)
SHIMAHARA AKIKO (JP)
NEYA MASAHIRO (JP)
Application Number:
PCT/JP2018/047748
Publication Date:
July 04, 2019
Filing Date:
December 26, 2018
Export Citation:
Assignee:
KNC LABORATORIES CO LTD (JP)
International Classes:
C07F9/24; C07H19/10; C07H19/20; C07H21/04
Domestic Patent References:
| WO2017057540A1 | 2017-04-06 | |||
| WO2017086397A1 | 2017-05-26 | |||
| WO1998020018A1 | 1998-05-14 | |||
| WO2017104836A1 | 2017-06-22 | |||
| WO2005008859A1 | 2005-01-27 | |||
| WO2004058779A1 | 2004-07-15 | |||
| WO2016006697A1 | 2016-01-14 | |||
| WO2012157723A1 | 2012-11-22 |
Foreign References:
| JP2006512386A | 2006-04-13 | |||
| JP2010275254A | 2010-12-09 | |||
| JP2010513358A | 2010-04-30 | |||
| JP2011121881A | 2011-06-23 | |||
| JP2010024228A | 2010-02-04 | |||
| JP2001253986A | 2001-09-18 |
Other References:
PALTE MICHAEL J., ET AL.: "Interaction of Nucleic Acids with the Glycocalyx", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 134, no. 14, 8 March 2012 (2012-03-08), pages 6218 - 6223, XP055623404, ISSN: 0002-7863
NATT FRANÇOIS ET AL.: "Lipocap: a Lipophilic Phosphoramidite-based Capping Reagent", TETRAHEDRON, vol. 53, no. 28, 1997, pages 9629 - 9636, XP004105893
NUCLEIC ACIDS RESEARCH, vol. 18, 1990, pages 3155 - 3159
TETRAHEDRON LETT, vol. 32, no. 27, 1991, pages 3251 - 3254
NUCLEIC ACIDS RESEARCH, vol. 21, no. 5, 1993, pages 1213 - 1217
CHEM. EUR. J., vol. 19, 2013, pages 8615 - 8620
TETRAHEDRON LETTERS, vol. 50, no. 15, 2009, pages 1751 - 1753
NUCLEIC ACIDS RESEARCH, vol. 14, no. 16, 1986, pages 6453 - 6470
TETRAHEDRON LETT, vol. 52, 2011, pages 434 - 437
TETRAHEDRON LETT, vol. 35, no. 46, 1994, pages 8565 - 8568
TETRAHEDRON, vol. 53, no. 28, 1997, pages 9629 - 9636
MICKLEFIELD, CURRENT MEDICINAL CHEMISTRY, vol. 8, 2001, pages 1157 - 1170
"Protective Group In Organic Synthesis", 1999, JOHN WILLY & SONS
See also references of EP 3733680A4
NATT FRANÇOIS ET AL.: "Lipocap: a Lipophilic Phosphoramidite-based Capping Reagent", TETRAHEDRON, vol. 53, no. 28, 1997, pages 9629 - 9636, XP004105893
NUCLEIC ACIDS RESEARCH, vol. 18, 1990, pages 3155 - 3159
TETRAHEDRON LETT, vol. 32, no. 27, 1991, pages 3251 - 3254
NUCLEIC ACIDS RESEARCH, vol. 21, no. 5, 1993, pages 1213 - 1217
CHEM. EUR. J., vol. 19, 2013, pages 8615 - 8620
TETRAHEDRON LETTERS, vol. 50, no. 15, 2009, pages 1751 - 1753
NUCLEIC ACIDS RESEARCH, vol. 14, no. 16, 1986, pages 6453 - 6470
TETRAHEDRON LETT, vol. 52, 2011, pages 434 - 437
TETRAHEDRON LETT, vol. 35, no. 46, 1994, pages 8565 - 8568
TETRAHEDRON, vol. 53, no. 28, 1997, pages 9629 - 9636
MICKLEFIELD, CURRENT MEDICINAL CHEMISTRY, vol. 8, 2001, pages 1157 - 1170
"Protective Group In Organic Synthesis", 1999, JOHN WILLY & SONS
See also references of EP 3733680A4
Attorney, Agent or Firm:
YAMAO, Norihito et al. (JP)
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