WO2004007513A1 - Method for producing 2-deoxy-l-ribose - Google Patents
Method for producing 2-deoxy-l-ribose Download PDFInfo
- Publication number
- WO2004007513A1 WO2004007513A1 PCT/KR2003/001398 KR0301398W WO2004007513A1 WO 2004007513 A1 WO2004007513 A1 WO 2004007513A1 KR 0301398 W KR0301398 W KR 0301398W WO 2004007513 A1 WO2004007513 A1 WO 2004007513A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- deoxy
- ribose
- alkyl
- acid
- alcohol
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/08—Deoxysugars; Unsaturated sugars; Osones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/02—Monosaccharides
Definitions
- the present invention relates to a synthetic method for the compound having compound (1) below, more specifically, to a mass-produceable and cost-effective synthetic method of compound (1) from 2-Deoxy-D-ribose with easy reaction, separation, and purification.
- compound (1)
- L-nucleosides are attracting attention as antiviral agents.
- Some L-nucleosides such as L-thymidine, L-2'-thiacytidine (3TC) and L- 2',3'-dideoxycytidine (L-ddC) are much less toxic and have better antiviral activity than their D-isomers.
- L-nucleosides have good effect in antisense oligonucleotide therapy.
- the objective of the present invention is to provide a synthetic process of 2-deoxy-L-robse, which allows the cost-effective and large-scale synthesis thanks to the short process, the easy reaction and purification.
- the present invention provides the synthetic process of compound (1) comprising 4 steps; protection, activation and inversion of 3- and 4-OH groups of 2-deoxy-D-ribose, and deprotection.
- the present invention provides the synthetic process of compound (1) comprising the steps of; (A) protection step in which aldehyde group of 2-deoxy-D-ribose is protected in the form of acetal. 2-deoxy-l-O-alkyl-D-ribopyranoside is prepared by the reaction of 2-deoxy-D-ribose with alcohol in the presence of acid; (B) activation step in which 3 -and 4-OH groups of 2-deoxy-D-ribose are activated.
- 2-deoxy-l-O-alkyl- 3 ,4-di-(alkanesulfonyl)-D-ribose or 2-deoxy- 1 -O-alkyl-3 ,4-di-(arylsulfonyl)-D-ribose is prepared by reaction of the above 2-deoxy-l-O-alkyl-D-ribose with organic sulfonylhalide for activation of 3- and 4-OH; (C) inversion step in which stereochemistry of 3- and 4-OH groups is changed.
- protecting group is introduced in the form of acetal by the reaction of compound (2), 2-deoxy-D-ribose with alcohol in the presence of acid.
- RI represents a lower alkyl having 1-5 of carbon number, a benzyl or a substituted benzyl.
- the acid used in this step contains inorganic acid such as hydrochloric acid and sulfuric acid or organic acid such as methanesulfonic acid and p- toluenesulfonic acid and the concentration of acid is preferably 1 ⁇ 10%.
- a lower alcohol such as methyl alcohol, ethyl alcohol, propyl alcohol and butyl alcohol, benzyl alcohol or substituted benzyl alcohol may be used.
- compound (4), 2-deoxy-l-O-alkyl-3,4-di-(alkanesulfonyl)-D-ribose or 2-deoxy-l-O-alkyl-3,4-di-(arylsulfonyl)-D-ribose is obtained by converting 3- and 4-
- An organic sulfonyl halide used in this step may include a lower alkanesulfonyl halide such as methanesulfonyl chloride and trifluoromethylsulfonyl chloride and arylsulfonyl halide such as bezenesulfonyl chloride and p-toluenesulfonylchloride.
- a lower alkanesulfonyl halide such as methanesulfonyl chloride and trifluoromethylsulfonyl chloride
- arylsulfonyl halide such as bezenesulfonyl chloride and p-toluenesulfonylchloride.
- RI represents a lower alkyl having 1-8 of carbon number, a substituted or unsubstituted benzyl and R2 represents a lower alkylsulfonyl having 1-8 of carbon number, a substituted or unsubstituted aryl sulfonyl group.
- a metal salt of organic acid used in this step may include a metal salt of lower alkyl organic acid such as sodium acetate, potassium acetate or a metal salt of aryl organic acid such as sodium benzoate or potassium benzoate.
- a solvent used in this step may include water and organic solvent such as dimethylforrnamide (DMF), dimethylacetamide (DMAC), and alohols, but DMF or the mixture of water and organic solvent is preferable in view of solubility of the reactants.
- DMF dimethylforrnamide
- DMAC dimethylacetamide
- alohols but DMF or the mixture of water and organic solvent is preferable in view of solubility of the reactants.
- RI represents a lower alkyl having 1-8 of carbon number, a substituted or unsubstituted benzyl and R2 represents a lower alkylsulfonyl having 1-8 of carbon number, a substituted or unsubstituted aryl sulfonyl group.
- Compound (1) can be used as a raw material for the further reaction without purification or can be purified by the formation of anilide derivative well known as a purification method of 2-deoxy-D-ribose to obtain as solid
- R3 lower alkyl having 1-8 of carbon number or substituted or unsubstituted benzyl ]
- Embodiment 2 Activation of 3- and 4-OH groups: Preparation of 2-Deoxy-l-O-butyl-3,4-di-(p- toluenesulfonyl)-D-ribose
- Embodiment 3 Conversion to L-form sugar from D-form sugar: Preparation of 2-deoxy-l-O- butyl-3-benzoyl-L-ribose and 2-deoxy-l-O-butyl-4-benzoyl-L-ribose
- Embodiment 2 To the compound obtained in Embodiment 2 (20g) were added n-butanol (7 mL), water (4.4mL), N,N-dimethylformamide (27.6 mL) and potassium benzoate (21.2g) and the mixture was heated to 115°C and reacted for 8 hours. After the concentration of the reaction mixture, water and ethyl acetate were added to separate organic and water layers. After the organic layer was concentrated, the residue was mixed with water and evaporated again to concentrate N,N-dimethylformamide efficiently. The residue was used for the next reaction.
- Embodiment 3 To the residue obtained in Embodiment 3 were added water (10 mL) and 40% sodium hydroxide solution (10 mL) and the mixture was stirred for 3 hours at room temperature. 6N hydrochloric acid (50mL) was added to the reaction mixture and the resulting mixture was stirred for 4 hours at 25 ⁇ 30 °C to give 2-deoxy-L-ribose.
- 6N hydrochloric acid 50mL was added to the reaction mixture and the resulting mixture was stirred for 4 hours at 25 ⁇ 30 °C to give 2-deoxy-L-ribose.
- anilide derivative which was already known for its enatiomer 2-deoxy-D-ribose, pure 2-deoxy-L-ribose was obtained as solid (3.4g).
- the present invention is related to the synthetic method for 2-deoxy-L-ribose in which reaction and purification is easy at easily attainable range of temperature and pressure, and of which reagents are more cheap and less toxic. Additionally, this invention provides more economic method than the previously known process in terms of the costs for equipments, law-materials, and processing by using the low-cost and non-toxic reagents starting from 2-deoxy-D-ribose which is naturally abundant as well as can be synthesized from D-glucose easily.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002492558A CA2492558A1 (en) | 2002-07-15 | 2003-07-15 | Method for producing 2-deoxy-l-ribose |
AU2003281047A AU2003281047A1 (en) | 2002-07-15 | 2003-07-15 | Method for producing 2-deoxy-l-ribose |
US10/521,022 US7304154B2 (en) | 2002-07-15 | 2003-07-15 | Method for producing 2-deoxy-L-ribose |
JP2004521271A JP2005538080A (en) | 2002-07-15 | 2003-07-15 | Method for synthesizing 2-deoxy-L-ribose |
EP03741579A EP1556396A4 (en) | 2002-07-15 | 2003-07-15 | Method for producing 2-deoxy-l-ribose |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2002-0041378 | 2002-07-15 | ||
KR10-2002-0041378A KR100446560B1 (en) | 2002-07-15 | 2002-07-15 | Method for Producing 2-Deoxy-L-ribose |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004007513A1 true WO2004007513A1 (en) | 2004-01-22 |
Family
ID=30113183
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2003/001398 WO2004007513A1 (en) | 2002-07-15 | 2003-07-15 | Method for producing 2-deoxy-l-ribose |
Country Status (8)
Country | Link |
---|---|
US (1) | US7304154B2 (en) |
EP (1) | EP1556396A4 (en) |
JP (1) | JP2005538080A (en) |
KR (1) | KR100446560B1 (en) |
CN (1) | CN1668626A (en) |
AU (1) | AU2003281047A1 (en) |
CA (1) | CA2492558A1 (en) |
WO (1) | WO2004007513A1 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100849979B1 (en) | 2006-12-06 | 2008-08-01 | 주식회사 삼천리제약 | The preparation method of 2-deoxy-L-ribose |
CN102153600B (en) * | 2010-02-12 | 2016-09-14 | 何遂庆 | The preparation method of 2-deoxidation-L-ribose |
CN107778334A (en) * | 2016-08-26 | 2018-03-09 | 康普药业股份有限公司 | A kind of preparation method of Sebivo key intermediate |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4675390A (en) * | 1984-12-03 | 1987-06-23 | Eli Lilly And Company | 2-deoxypentose derivatives |
US5220003A (en) * | 1991-03-29 | 1993-06-15 | The Regents Of The University Of California | Process for the synthesis of 2',3'-dideoxynucleosides |
US5659021A (en) * | 1987-03-13 | 1997-08-19 | The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations | Chiral glycerol derivatives |
WO1998039347A2 (en) * | 1997-03-05 | 1998-09-11 | The Regents Of The University Of California | Synthesis of l-ribose and 2-deoxy l-ribose |
KR20000008131A (en) * | 1998-07-10 | 2000-02-07 | 정낙신 | Thionucloside substitute and preparation method thereof |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6140498A (en) * | 1998-11-17 | 2000-10-31 | Xyrofin Oy | Process for the continuous production of high purity L-ribose |
DE10020275A1 (en) * | 2000-04-25 | 2001-10-31 | Manfred Schneider | New 2-deoxy-L-ribose and 2-deoxy-D-ribose precursors useful as intermediates for therapeutic nucleic acids and oligonucleotides |
KR100440461B1 (en) * | 2000-08-19 | 2004-07-15 | (주) 한켐 | Process for the preparation of L-ribose using 1,4-lactone |
KR100449310B1 (en) * | 2001-11-08 | 2004-09-18 | 주식회사 삼천리제약 | preparation method of 2-deoxy-L-ribose |
KR100433179B1 (en) * | 2001-11-10 | 2004-05-27 | 주식회사 삼천리제약 | Method for Producing 2-Deoxy-L-ribose |
-
2002
- 2002-07-15 KR KR10-2002-0041378A patent/KR100446560B1/en active IP Right Grant
-
2003
- 2003-07-15 WO PCT/KR2003/001398 patent/WO2004007513A1/en not_active Application Discontinuation
- 2003-07-15 EP EP03741579A patent/EP1556396A4/en not_active Withdrawn
- 2003-07-15 CA CA002492558A patent/CA2492558A1/en not_active Abandoned
- 2003-07-15 CN CNA038166062A patent/CN1668626A/en active Pending
- 2003-07-15 JP JP2004521271A patent/JP2005538080A/en active Pending
- 2003-07-15 AU AU2003281047A patent/AU2003281047A1/en not_active Abandoned
- 2003-07-15 US US10/521,022 patent/US7304154B2/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4675390A (en) * | 1984-12-03 | 1987-06-23 | Eli Lilly And Company | 2-deoxypentose derivatives |
US5659021A (en) * | 1987-03-13 | 1997-08-19 | The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations | Chiral glycerol derivatives |
US5220003A (en) * | 1991-03-29 | 1993-06-15 | The Regents Of The University Of California | Process for the synthesis of 2',3'-dideoxynucleosides |
WO1998039347A2 (en) * | 1997-03-05 | 1998-09-11 | The Regents Of The University Of California | Synthesis of l-ribose and 2-deoxy l-ribose |
KR20000008131A (en) * | 1998-07-10 | 2000-02-07 | 정낙신 | Thionucloside substitute and preparation method thereof |
Non-Patent Citations (1)
Title |
---|
See also references of EP1556396A4 * |
Also Published As
Publication number | Publication date |
---|---|
CA2492558A1 (en) | 2004-01-22 |
CN1668626A (en) | 2005-09-14 |
US7304154B2 (en) | 2007-12-04 |
KR100446560B1 (en) | 2004-09-04 |
EP1556396A1 (en) | 2005-07-27 |
KR20040006826A (en) | 2004-01-24 |
JP2005538080A (en) | 2005-12-15 |
US20050176950A1 (en) | 2005-08-11 |
AU2003281047A1 (en) | 2004-02-02 |
EP1556396A4 (en) | 2007-10-24 |
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