WO1991010665A1 - Production de carboxetanocine g ou a et intermediaires de ces composes - Google Patents

Production de carboxetanocine g ou a et intermediaires de ces composes Download PDF

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Publication number
WO1991010665A1
WO1991010665A1 PCT/JP1990/000235 JP9000235W WO9110665A1 WO 1991010665 A1 WO1991010665 A1 WO 1991010665A1 JP 9000235 W JP9000235 W JP 9000235W WO 9110665 A1 WO9110665 A1 WO 9110665A1
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WO
WIPO (PCT)
Prior art keywords
compound
formula
solvent
group
represented
Prior art date
Application number
PCT/JP1990/000235
Other languages
English (en)
Japanese (ja)
Inventor
Mikio Honjo
Tokumi Maruyama
Yoshiko Sato
Original Assignee
Nippon Kayaku Kabushiki Kaisha
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 Nippon Kayaku Kabushiki Kaisha filed Critical Nippon Kayaku Kabushiki Kaisha
Publication of WO1991010665A1 publication Critical patent/WO1991010665A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C219/24—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups or amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the present invention has an antiviral activity and is expected to be a carboxycetanosin G or carboxetanosin A which is expected as an anti-inflammatory agent. And the intermediates thereof.
  • Alisteromycin which is a natural-derived adenocine canoleposic analytic (T. Kusaka et al., J. Antibiot .. 21, 25) 5 (1 9 6 8)) ⁇ Neplanosin (S.
  • the present invention firstly uses the formula (I)
  • a compound of the formula ( ⁇ ) characterized by reacting a compound represented by the formula (1) with an alkali hydroxide and then with an acid.
  • the present invention uses the formula 8 Wherein a compound represented by the formula is reacted with an alkali hydroxide.
  • the present invention provides a method for producing carboxoxetanosin A represented by CHiff0H, and the present invention provides a compound of formula 5
  • examples of the alkali metal hydroxide include alkali metal hydroxides such as sodium hydroxide, lithium hydroxide, and potassium hydroxide. Salt is exaggerated, but sodium hydroxide is common and preferred.
  • the amount of the compound to be used may be, for example, 1.5 ml or more as a 1N solution of the compound of the formula (I) 0.44 ⁇ 1, but usually about 2 ml. .
  • the reaction temperature is not particularly limited, but room temperature is sufficient.
  • the solvent of the compound of the formula (I) is not particularly limited as long as the compound of the formula (I) dissolves and does not adversely affect the reaction, and examples thereof include dioxane. It is terrible.
  • Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid, and usic acid, and hydrochloric acid is generally preferred.
  • the amount used will vary depending on the amount of alkali hydroxide used in the previous step, but usually more than 2 ml of 1N hydrochloric acid per 0.44 niniol of the compound of formula (I) However, about 3 ml is practically preferable.
  • the reaction with the acid is carried out by adding the acid to the reaction solution obtained by the reaction with the sodium hydroxide and concentrating the mixture, preferably at the boiling point of the solvent, preferably. , Just do it.
  • the compound of the formula (I) as a starting material can be obtained by the following reaction route using the compound of the formula 5a described below as a starting material.
  • the hydroxylated alkali in the second invention the same one as that obtained in the first invention is obtained, and sodium hydroxide is used.
  • the amount of the compound used is not less than 0.7 ml as a 1N aqueous solution for 0.23 mmo 1 of the compound of the formula 8, but usually About 1 ml is used.
  • the reaction temperature is not particularly limited, but room temperature is sufficient.
  • a solvent for the reaction there is no particular limitation as long as the compound of the formula 8 dissolves and does not adversely affect the reaction.
  • the compound of the formula 8 dissolves and does not adversely affect the reaction.
  • methanol, ethanol, etc. The report is broken.
  • the compound of the formula 8 can be obtained by the following reaction route using the compound of the formula 5a described below as a starting material.
  • examples of the hydroxyl-protecting group in the general formula 5 include, for example, an acyl group, a benzyl group, a silinole group and a trityl group.
  • the throat is broken.
  • examples of the acyl group include an acetyl group, a propylion group, a petityl group, an isopropylcarbonyl group, and a pennylcarbonyl group. Do etc.
  • silino group examples include a t-butyl dimethyl group, a t-butyl group and a triphenyl group, and a triphenyl group.
  • Examples include the dimethylsilyl group, the methyldiisopropynolyl group, and the triisopropylsilyl group.
  • Specific compounds include, for example, 11-amino-2,3-vis (cyclohexanol), cyclobutane, and the like. can give .
  • This compound is a known compound of the following formula 1 (K.C.
  • the solvent of the second fraction was distilled off, and the residue was crystallized from ethyl acetate to give 5a (301.6 ing, 20.2%) white in color. It was white.
  • Compound 8 as a raw material could be obtained by the following method using Compound 5a obtained by the method of Example 1 as a raw material.
  • the compound (8) was obtained as white crystals (127 rag, 88%) by BB formation.
  • the starting compound (I) could be obtained by the following method using the compound 5a obtained by the method of Example 1 as the starting material.
  • Raw material compound 5a4 3 1 mg (1.23 mniol) and 2-amino-4,6-dichloropyrimidine 20 2 nig (1.23 mraol) are n- Soluble to a mixture of butanole (5 ml), methanol (0.5 ml) and tritinoleamine (1.5 ml), and heat for 11 hours Shed.
  • Calboxoxetanocins A and G obtained by the method of the present invention were held on June 4-19, 1989 in Montreal, Canada. At the 5th International AIDS Conference, Its efficacy has been announced, and it is expected to be used as an antiviral agent for AIDS treatment.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention se rapporte à un procédé de production de carboxétanocine G, qui est un composé représenté par la formule (II), ou de carboxétanocine A, qui est un composé représenté par la formule (9), ces composés étant chacun prévu comme agents antiviraux, ainsi qu'à des dérivés de cyclobutane comme intermédiaires de ces composés, représentés par la formule (5), où P représente des groupes protecteurs hydroxyle.
PCT/JP1990/000235 1990-01-12 1990-02-27 Production de carboxetanocine g ou a et intermediaires de ces composes WO1991010665A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2/3436 1990-01-12
JP2003436A JP2898326B2 (ja) 1990-01-12 1990-01-12 カルボオキセタノシンｇの合成法

Publications (1)

Publication Number Publication Date
WO1991010665A1 true WO1991010665A1 (fr) 1991-07-25

Family

ID=11557308

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1990/000235 WO1991010665A1 (fr) 1990-01-12 1990-02-27 Production de carboxetanocine g ou a et intermediaires de ces composes

Country Status (3)

Country Link
JP (1) JP2898326B2 (fr)
CA (1) CA2049047A1 (fr)
WO (1) WO1991010665A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000069806A1 (fr) * 1999-05-17 2000-11-23 Lonza Ag Procede de preparation d'amines chirales

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6284086A (ja) * 1985-08-16 1987-04-17 グラクソ・グル−プ・リミテツド グアニン誘導体

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6284086A (ja) * 1985-08-16 1987-04-17 グラクソ・グル−プ・リミテツド グアニン誘導体

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEM. PHARM. BULL., Vol. 37, No. 5, (May 1989) (Japan), M. HONJO et al., "Synthesis of the Carbocyclic Analog of Oxetanocin A", pages 1413-1415. *

Also Published As

Publication number Publication date
CA2049047A1 (fr) 1991-07-13
JPH03215486A (ja) 1991-09-20
JP2898326B2 (ja) 1999-05-31

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