WO2001072698A1 - Derives optiquement actifs de cyanobutantriol et procede de fabrication de ceux-ci - Google Patents

Derives optiquement actifs de cyanobutantriol et procede de fabrication de ceux-ci Download PDF

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Publication number
WO2001072698A1
WO2001072698A1 PCT/KR2001/000354 KR0100354W WO0172698A1 WO 2001072698 A1 WO2001072698 A1 WO 2001072698A1 KR 0100354 W KR0100354 W KR 0100354W WO 0172698 A1 WO0172698 A1 WO 0172698A1
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WIPO (PCT)
Prior art keywords
compound
formula
preparing
present
reaction
Prior art date
Application number
PCT/KR2001/000354
Other languages
English (en)
Inventor
Young-Ro Choi
Kwan-Soo Kim
Jin-Whan Kim
Original Assignee
Kukje Pharma. Ind. Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kukje Pharma. Ind. Co., Ltd. filed Critical Kukje Pharma. Ind. Co., Ltd.
Publication of WO2001072698A1 publication Critical patent/WO2001072698A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/32—Oxygen atoms
    • C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/11—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/11—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton
    • C07C255/12—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton containing cyano groups and hydroxy groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • the present invention relates to an optically active (2S,3R)-4-cyanobutan-l,2,3- triol derivative represented by the following formula (1):
  • R and R independently of one another represent hydrogen or hydroxy-protecting group, or to a process for preparing same.
  • the present invention further relates to a process for preparing the compound of formula (2) from the precursor compound of formula (1).
  • the compound of formula (2) is known in The Journal of Organic Chemistry, 53, 1988, 2598 and The Journal of Organic Chemistry, 55, 1990, 4400; useful in the research for protein-DNA interaction; used as a constituent unit of the important antisense medicines such as enantio-DNA or meso-DNA; and very useful as the intermediate for L- nucleoside drugs which are expected to have a new biological activity.
  • the desired compound of 2-deoxy-Z-ribose (2) is produced from the starting epoxy compound via the dithiane compound as an intermediate.
  • n-butyllithium should be used as a base.
  • this is a very difficult process for being applied in an industrial mass production, and thus, is not recommended.
  • one object of the present invention is to provide the (2S,3R)-4- cyanobutan-l,2,3-triol derivative of the above formula (1).
  • the present invention provides a (2S,3R)-4-cyanobutan-l,2,3-triol derivative of the following formula (1): in which R and R' independently of one another represent hydrogen or hydroxy-protecting group.
  • any typical one in the technical field to which the present invention pertains can be used without any restriction. But, isopropylidene, cyclohexylidene, benzylidene and benzyl are preferable and isopropylidene among them is most convenient and economic.
  • the present invention also provides a process for preparing the compound of formula (1).
  • the compound of formula (1) can be conveniently prepared by introducing a cyano group into an epoxy compound represented by the following formula (3):
  • the compound of formula (3) used as a starting material in the above reaction can easily be prepared according to the method described in Journal of the Korean Chemical Society, 38, 11 (1994). It is preferable to use alkali metal cyanide as the cyano group-introducing agent, and sodium cyanide or potassium cyanide among them is particularly preferable.
  • This cyano group-introducing agent is used in an amount of 2 to 10 equivalents, preferably 6 to 10 equivalents with respect to the compound of formula (3). If it is used in an amount of less than 2 equivalents, there are some problems that the reaction time is increased and side reactions may occur. If it is used in an amount of more than 10 equivalents, it is uneconomic because there is no increase in the effect depending on the increase of the amount used.
  • the above reaction is optionally carried out in a solvent that does not adversely affect the reaction, and as the solvent preferable for such purpose, methanol, ethanol, 2- propanol, N,N-dimethylformamide can be mentioned. Methanol is most preferable.
  • the reaction may be carried out at a temperature ranging from 0 to 60 ° C, suitably for about a day. However, room temperature is most preferable.
  • the present invention further provides a process for preparing 2-deoxy- -ribose of formula (2) from the novel compound of formula (1) as depicted in the following Reaction Scheme 3.
  • the hydrolysis reaction of the above Reaction Scheme 3 may be carried out by warming the reactants in aqueous sodium hydroxide solution to form a lactone, and the reduction reaction can be proceeded under the specific reaction conditions disclosed in Org. Syn. Vol 1, 321 and Bull. Chem. Jpn, Vol 45, 2624-2634 (1972).
  • the reduction reaction is carried out in a solvent such as tetrahydrofuran using disiamylborane [(Sia) 2 BH] as a reducing agent.
  • a solvent such as tetrahydrofuran using disiamylborane [(Sia) 2 BH] as a reducing agent.
  • Example 1 was dissolved in 90 ml of acetonitrile. 9 mi of lN-hydrochloric acid solution was added thereto and the resulting mixture was stirred for 1 hour at 40 °C . The solvent was removed by distillation under reduced pressure and the residue was dissolved in 15 ml* of distilled water. 2.34g of sodium hydroxide dissolved in 15 m of distilled water and cooled to 0°C was slowly added thereto. The mixture was warmed to 80 °C and stirred for 4 hours. The solvent was removed by distillation under reduced pressure and to the residue were added 14 ml. of distilled water and 1.6 ml* of cone, sulfuric acid. 50 ml* of methanol was added, stirred, and filtered. Again, 50 mi of tetrahydrofuran was added, stirred, and filtered. The solvent was distilled under reduced pressure to give 5.92g(Y ⁇ eld 88.3%) of the title compound.
  • the organic layer was separated from the reaction solution and the aqueous layer was washed with diethylether (300 mix3).
  • the aqueous layer was concentrated under reduced pressure, the concentrate was dissolved in 100 ml, of methanol, and the solvent was removed by distillation under reduced pressure. This procedure was repeated three times. The residue thus obtained was dissolved again in 100 ml, of ethanol and then filtered. The solvent was distilled under reduced pressure to give 3.37g(Y ⁇ eld 56%) of the title compound.
  • the compound of formula (1) newly provided by the present invention can be advantageously used for the industrial mass production of 2-deoxy-J-ribose, which is a useful intermediate in the field of manufacture of medicines.

Abstract

La présente invention concerne un dérivé optiquement actif de (2S,3R)-4-cyanobutane-1,2,3-triol, un procédé de fabrication de ce composé, ainsi qu"un procédé de fabrication de 2-désoxy-L-ribose à partir dudit composé.
PCT/KR2001/000354 2000-03-27 2001-03-07 Derives optiquement actifs de cyanobutantriol et procede de fabrication de ceux-ci WO2001072698A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR2000/15512 2000-03-27
KR10-2000-0015512A KR100367986B1 (ko) 2000-03-27 2000-03-27 광학활성을 갖는 시아노부탄트리올 유도체 및 그의 제조방법

Publications (1)

Publication Number Publication Date
WO2001072698A1 true WO2001072698A1 (fr) 2001-10-04

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PCT/KR2001/000354 WO2001072698A1 (fr) 2000-03-27 2001-03-07 Derives optiquement actifs de cyanobutantriol et procede de fabrication de ceux-ci

Country Status (2)

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KR (1) KR100367986B1 (fr)
WO (1) WO2001072698A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6960680B2 (en) 2003-01-08 2005-11-01 Rhodia Chirex, Inc. Manufacture of water-soluble β-hydroxynitriles
US7595390B2 (en) 2003-04-28 2009-09-29 Novartis Ag Industrially scalable nucleoside synthesis
EP2157095A2 (fr) 2003-06-30 2010-02-24 Novartis Ag Synthèse de bêta-L-2-désoxynucléosides

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100449310B1 (ko) * 2001-11-08 2004-09-18 주식회사 삼천리제약 2-데옥시-ｌ-리보스의 제조방법
KR100433179B1 (ko) * 2001-11-10 2004-05-27 주식회사 삼천리제약 2-데옥시-ｌ-리보오스의 제조방법

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11228453A (ja) * 1998-02-18 1999-08-24 Japan Science & Technology Corp ホモアリルアルコール類の製造方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11228453A (ja) * 1998-02-18 1999-08-24 Japan Science & Technology Corp ホモアリルアルコール類の製造方法

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CARL H. BEHRENS ET AL.: "Selective transformation of 2,3-epoxy alcohols and related derivatives. Strategies for nucleophilic attack at carbon-1", JOURNAL OF ORGANIC CHEMISTRY, vol. 15, no. 26, 1985, pages 5687 - 5696 *
HARRIE J.M. GIJIN ET AL.: "Sequential three- and four-substrate aldol reactions catalyzed by aldolases", JOURNAL OF AMERICAN CHEMICAL SOCIETY, vol. 117, no. 29, 1995, pages 7585 - 7591, XP002195226, DOI: doi:10.1021/ja00134a001 *
LIHREN CHEN ET AL.: "Deoxyribose-5-phosphate aldolase as a catalyst in asymmetric aldol condensation", JOURNAL OF AMERICAN CHEMICAL SOCIETY, vol. 114, no. 2, 1992, pages 741 - 748, XP002195227, DOI: doi:10.1021/ja00028a050 *
SEGIO J. CORTES ET AL.: "The 180 isotope shift in 13C nuclear magnetic resonance spectroscopy. 14. Kinetics of oxygen exchange at the anomeric carbon of D-ribose and D-2-deoxyribose", JOURNAL OF ORGANIC CHEMISTRY, vol. 56, no. 3, 1991, pages 943 - 947 *
THEODORA W. GREENE ET AL.: "john wiley & sons, inc.", 1991 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6960680B2 (en) 2003-01-08 2005-11-01 Rhodia Chirex, Inc. Manufacture of water-soluble β-hydroxynitriles
US7595390B2 (en) 2003-04-28 2009-09-29 Novartis Ag Industrially scalable nucleoside synthesis
EP2157095A2 (fr) 2003-06-30 2010-02-24 Novartis Ag Synthèse de bêta-L-2-désoxynucléosides

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Publication number Publication date
KR20010092864A (ko) 2001-10-27
KR100367986B1 (ko) 2003-01-14

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