Title:
OPTICALLY ACTIVE OLIGONUCLEIC ACID COMPOUND CONTAINING PHOSPHOROTHIOATE BOND
Document Type and Number:
WIPO Patent Application WO/2006/043521
Kind Code:
A1
Abstract:
This invention provides novel nucleic acid dimer compounds useful for the production of optically active oligonucleic acid compounds containing a phosphorothioate bond. The optically active nucleic acid dimer compounds are represented by general formula (2a) or (2b): (2a) (2b) wherein Bx1 and Bx2 represent a nucleic acid base optionally containing a protective group; R1a1 and R1a2 represent hydrogen or the like; and R2 represents acyl or a substituent represented by general formula (3a) or (3b): (3a) (3b) wherein R2a and R2b, which may be the same or different, represent alkyl, or R2a and R2b combine with an adjacent nitrogen atom to represent a five- or six-membered saturated amino ring group; R2d represents aryl or a mono- or dicyclic heterocyclic group; and R2c and R2e represent alkyl; R3 represents alkyl, aryl or a mono- or dicyclic heterocyclic group; and R4 represents hydrogen or a group which is eliminated under acidic conditions.
Inventors:
YANO JUNICHI (JP)
OHGI TADAAKI (JP)
UEDA TOSHIHIRO (JP)
OHGI TADAAKI (JP)
UEDA TOSHIHIRO (JP)
Application Number:
PCT/JP2005/019074
Publication Date:
April 27, 2006
Filing Date:
October 18, 2005
Export Citation:
Assignee:
NIPPON SHINYAKU CO LTD (JP)
YANO JUNICHI (JP)
OHGI TADAAKI (JP)
UEDA TOSHIHIRO (JP)
YANO JUNICHI (JP)
OHGI TADAAKI (JP)
UEDA TOSHIHIRO (JP)
International Classes:
C07H21/04; A61K9/127; C07H21/00; C07H21/02; C12N15/09
Domestic Patent References:
| WO2001040515A1 | 2001-06-07 |
Foreign References:
| JP2000290291A | 2000-10-17 |
Other References:
ALMER H ET AL: "A new approach to stereospecific synthesis of P-chiral phosphorothioates. Preparation of diastereomeric dithymidyl-(3 -5 ) phosphorothioates.", CHEMICAL COMMUNICATIONS., no. 3, February 2004 (2004-02-01), pages 290 - 291, XP002993810
WANG ZF ET AL: "Synthesis of dinucleoside, di(2'-deoxy-2'-fluoro)nucleoside phosphates and phosphorothioates and their stability to snake venom phosphodiesterase.", CHINESE JOURNAL OF CHEMISTRY., vol. 14, no. 1, 1996, pages 80 - 86, XP009004571
YANG X B ET AL: "DEOXYXYLOTHYMIDINE 3' -O-PHOSPHOROTHIOATES : SYNTHESIS, STEREOCHEMISTRY AND STEREOCONTROLLED INCORPORATION INTO OLIGOTHYMIDYLATES.", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS., vol. 7, no. 20, 1997, pages 2651 - 2656, XP004136505
IYER RP ET AL: "Methyl Phosphotriester Oligonucleotides: Facile Synthesis Using N-Pent-4-enoyl Nucleoside Phosphoramidites.", THE JOURNAL OF ORGANIC CHEMISTRY., vol. 60, no. 25, 1995, pages 8132 - 8133, XP002018376
GACS-BAITZ E ET AL: "Configurational Determination and Conformational Properties of Diastereomeric Nucleoside-Phosphorothioates.", TETRAHEDRON: ASYMETRY., vol. 7, no. 8, 1996, pages 2447 - 2452, XP002993811
CHERUVALLATH ZS ET AL: "SULFUROZATION EFFICIENCY IN THE SOLUTION PHASE SYNTHESIS OF DEOXYRIBONUCLEOSIDE PHOSPHOROTHIOATES-COMPARISON OF SULFUR TRIETHYLAMINE WITH VARIOUS SULFURIZING AGENTS.", NUCLEOSIDES & NUCLEOTIDES., vol. 15, no. 9, 1996, pages 1441 - 1445, XP000985455
FIDANZA JA ET AL: "Site-Specific Labeling of DNA Sequences Containing Phosphorothioate Diesters.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY., vol. 114, no. 14, 1992, pages 5509 - 5517, XP002993812
DATABASE CAPLUS [online] YANG XB ET AL: "Reactivity of nucleoside 5-O-phosphates, -phosphorothioates, -methanephosphonates, and -methanephosphonothioates toward activated xylonucleosides.", accession no. stn Database accession no. (1999:248628)
DATABASE CAPLUS [online] POTRZEBOWSKI MJ ET AL: "Synthesis and Structural Studies of SP and RP Diastereomers of Deoxyxylothymidyl-3-O-acetylthymidyl (3,5)-O-(2-Cyanoethyl)phosphorothioate in Solution and in the Solid State.", accession no. stn Database accession no. (2001:284611)
STEC WJ ET AL: "Deoxyribonucleoside 3'-O-(2-Thio- and 2-Oxo-"spiro"-4,4-pentamethylene-1,3,2-oxathiaphospholane)s: Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY., vol. 120, no. 29, 1998, pages 7156 - 7167, XP002239290
WANG ZF ET AL: "Synthesis of dinucleoside, di(2'-deoxy-2'-fluoro)nucleoside phosphates and phosphorothioates and their stability to snake venom phosphodiesterase.", CHINESE JOURNAL OF CHEMISTRY., vol. 14, no. 1, 1996, pages 80 - 86, XP009004571
YANG X B ET AL: "DEOXYXYLOTHYMIDINE 3' -O-PHOSPHOROTHIOATES : SYNTHESIS, STEREOCHEMISTRY AND STEREOCONTROLLED INCORPORATION INTO OLIGOTHYMIDYLATES.", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS., vol. 7, no. 20, 1997, pages 2651 - 2656, XP004136505
IYER RP ET AL: "Methyl Phosphotriester Oligonucleotides: Facile Synthesis Using N-Pent-4-enoyl Nucleoside Phosphoramidites.", THE JOURNAL OF ORGANIC CHEMISTRY., vol. 60, no. 25, 1995, pages 8132 - 8133, XP002018376
GACS-BAITZ E ET AL: "Configurational Determination and Conformational Properties of Diastereomeric Nucleoside-Phosphorothioates.", TETRAHEDRON: ASYMETRY., vol. 7, no. 8, 1996, pages 2447 - 2452, XP002993811
CHERUVALLATH ZS ET AL: "SULFUROZATION EFFICIENCY IN THE SOLUTION PHASE SYNTHESIS OF DEOXYRIBONUCLEOSIDE PHOSPHOROTHIOATES-COMPARISON OF SULFUR TRIETHYLAMINE WITH VARIOUS SULFURIZING AGENTS.", NUCLEOSIDES & NUCLEOTIDES., vol. 15, no. 9, 1996, pages 1441 - 1445, XP000985455
FIDANZA JA ET AL: "Site-Specific Labeling of DNA Sequences Containing Phosphorothioate Diesters.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY., vol. 114, no. 14, 1992, pages 5509 - 5517, XP002993812
DATABASE CAPLUS [online] YANG XB ET AL: "Reactivity of nucleoside 5-O-phosphates, -phosphorothioates, -methanephosphonates, and -methanephosphonothioates toward activated xylonucleosides.", accession no. stn Database accession no. (1999:248628)
DATABASE CAPLUS [online] POTRZEBOWSKI MJ ET AL: "Synthesis and Structural Studies of SP and RP Diastereomers of Deoxyxylothymidyl-3-O-acetylthymidyl (3,5)-O-(2-Cyanoethyl)phosphorothioate in Solution and in the Solid State.", accession no. stn Database accession no. (2001:284611)
STEC WJ ET AL: "Deoxyribonucleoside 3'-O-(2-Thio- and 2-Oxo-"spiro"-4,4-pentamethylene-1,3,2-oxathiaphospholane)s: Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY., vol. 120, no. 29, 1998, pages 7156 - 7167, XP002239290
Attorney, Agent or Firm:
Shimizu, Naoto (NIPPON SHINYAKU CO. LTD., 14, Kisshoin
Nishinosho Monguchicho, Minami-k, Kyoto-shi Kyoto 50, JP)
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