WO2023082429A1 - Procédé de synthèse pour 3-hydroxy-2-pyrone polysubstituée - Google Patents

Procédé de synthèse pour 3-hydroxy-2-pyrone polysubstituée Download PDF

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WO2023082429A1
WO2023082429A1 PCT/CN2021/139713 CN2021139713W WO2023082429A1 WO 2023082429 A1 WO2023082429 A1 WO 2023082429A1 CN 2021139713 W CN2021139713 W CN 2021139713W WO 2023082429 A1 WO2023082429 A1 WO 2023082429A1
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formula
compound
reaction
substituted
pyrone
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PCT/CN2021/139713
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Chinese (zh)
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王健
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台州学院
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
    • C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
    • C07F7/083—Syntheses without formation of a Si-C bond
    • 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 invention relates to the technical field of organic synthesis, in particular to a synthesis method of polysubstituted 3-hydroxyl-2-pyrone.
  • 3-Hydroxy-2-pyrone is a kind of pyrone compound. Due to its unique electronic effect, 3-hydroxy-2-pyrone can react with alkenes at room temperature under alkaline conditions[4+2] Cycloaddition reaction to build bridged ring compounds, and [4+2] cycloaddition/decarboxylation reaction with alkynes under mild conditions to build benzene rings.
  • the Chinese patent with publication number CN112778257A also discloses a green method for oxidizing furfuryl alcohol into dihydropyrone derivatives.
  • the method starts from furfuryl alcohol derivatives and obtains tetrahydropyran compounds through Achmatowicz rearrangement, and then The steps of epoxidation/Wharton rearrangement/oxidation can give 6-substituted-3-hydroxy-2-pyrone.
  • this method is easy to operate and does not involve anhydrous and oxygen-free reactions, it can only introduce substituents at the 6th position, which is difficult to meet the production requirements of multi-substituted products.
  • the problem to be solved in the present invention is to provide a kind of synthetic method of multi-substituted 3-hydroxyl-2-pyrone aiming at the above-mentioned deficiencies existing in the prior art, which achieves the synthesis of multi-substituted 3- The purpose of -hydroxy-2-pyrone.
  • a kind of synthetic method of substituted 3-hydroxyl-2-pyrone comprising the following steps,
  • R 1 and R 3 are hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, carbonyl or Carboxyl; R2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, carbonyl or carboxyl.
  • the method of the present invention introduces the R substituent at the No. 6 position on the basis of introducing the R1 substituent at the No. 6 position, and can introduce the R2 substituent at the No. 5 position with high selectivity through protecting group protection and multiple redox methods, It is enough to replace the R3 substituent at the 4th position.
  • the overall operation is convenient, does not involve anhydrous and oxygen-free operations, and the substrate is universal. While taking into account the yield, it achieves the synthesis of multi-substituted 3-hydroxyl - Purpose of 2-pyrone.
  • the process of Achmatowicz rearrangement reaction includes dissolving the compound of formula (I), potassium bromide and sodium bicarbonate, cooling down to -5-5°C, and adding potassium peroxymonosulfonate, Insulation reaction 0.5 ⁇ 1.5h, obtain formula (II) compound;
  • the mol ratio of described formula (I) compound, potassium bromide, sodium bicarbonate and potassium peroxymonosulfonate is 1:(0.04 ⁇ 0.06):(1.80 ⁇ 2.20): (1.20 ⁇ 1.40).
  • the mixed solvent (solvent) of the compound of formula (I) (furfuryl alcohol compound), potassium bromide, sodium bicarbonate, tetrahydrofuran and water in a volume ratio of 10:1 is sequentially dropped into the container, fully Stir for 30 minutes, then lower the temperature to -5 ⁇ 5°C, and gradually add potassium peroxymonosulfonate (Oxone) under the condition of sufficient stirring, and keep it warm for 0.5 ⁇ 1.5 hours; after the reaction is completed, add saturated sodium sulfite solution to quench the reaction, Then extract with ethyl acetate, separate the liquid, combine the organic phases, dry with sodium sulfate, filter and concentrate to obtain the compound of formula (II).
  • solvent solvent of the compound of formula (I) (furfuryl alcohol compound), potassium bromide, sodium bicarbonate, tetrahydrofuran and water in a volume ratio of 10:1 is sequentially dropped into the container, fully Stir for 30 minutes, then lower the temperature to -5 ⁇ 5°C,
  • the process of protecting with a protecting group includes dissolving the compound of formula (II) and pyridinium p-toluenesulfonate, adding vinyl ethyl ether, and reacting for 11-13 hours to obtain the compound of formula (III); wherein, The molar ratio of the compound of formula (II), pyridinium p-toluenesulfonate and vinyl ethyl ether is 1:(0.04-0.06):(1.80-2.20).
  • the process of the substitution reaction includes, after dissolving the compound of formula (III), cooling down to -5 ⁇ 5°C, and adding a nucleophile with R2 group, reacting for 2.5 ⁇ 3.5h, A compound of formula (IV) is obtained; wherein, the molar ratio of the compound of formula (III) to the nucleophile is 1: (1.40-1.60).
  • the nucleophilic reagent with R group is methyl Grignard reagent, vinyl Grignard reagent or phenyl Grignard reagent, preferably, the nucleophilic reagent with R group Methylmagnesium bromide, allylmagnesium bromide, ethylmagnesium bromide, lithium trimethylsilylacetylene or lithium 3-ethoxy-3-oxo-1-propyne.
  • the process of oxidative rearrangement reaction includes dissolving the compound of formula (IV) and sodium acetate, adding pyridinium chlorochromate at -5-5°C, and reacting for 2.5-3.5 hours, The compound of formula (V) is obtained; wherein, the molar ratio of the compound of formula (IV), sodium acetate and pyridinium chlorochromate is 1: (1.80-2.20): (1.40-1.60).
  • the carbonyl reduction reaction process includes dissolving the compound of formula (V), adding sodium borohydride at -5-5°C, and reacting for 2.5-3.5 hours to obtain the compound of formula (VI) ;
  • the molar ratio of the compound of formula (V) and sodium borohydride is 1: (1.40 ⁇ 1.60).
  • the process of removing the protecting group includes, after dissolving the compound of formula (VI), adding hydrochloric acid at -5-5°C, and reacting for 2.5-3.5 hours to obtain the compound of formula (VII); Wherein, the molar ratio of the compound of formula (VI) to hydrogen chloride in hydrochloric acid is 1: (1.10-1.40).
  • the oxidation reaction process includes, after dissolving the compound of formula (VII) and tetramethylpiperidine oxide, adding sodium hypochlorite at -5-5°C to obtain the compound of formula (VIII);
  • the molar ratio of the compound of formula (VII), tetramethylpiperidine oxide and sodium hypochlorite is 1: (0.04-0.14): (2.2-3.2).
  • the mixed solution (solvent) of the compound of formula (VII), tetramethylpiperidinium oxide (TEMPO), tetrahydrofuran and water in a volume ratio of 10:1 is sequentially put into the container, and fully stirred 30min, then lower the temperature to -5 ⁇ 5°C, and gradually add 10% sodium hypochlorite under the condition of full stirring, react for 2.5 ⁇ 3.5h; after the reaction is completed, add saturated sodium sulfite solution to the reaction solution to quench the reaction, and then use ethyl acetate After extraction, liquid separation and merging of the organic phases, drying with sodium sulfate, filtration and concentration, the compound of formula (VIII) was obtained.
  • the coupling reaction process includes, after dissolving the compound of formula (VIII), adding N-bromosuccinimide, reacting for 0.5-1.5h, and then raising the temperature under the action of palladium catalyst To 80 ⁇ 120 ° C, heat preservation reaction 3.5 ⁇ 4.5h, to obtain the compound of formula (IX); wherein, the molar ratio of the compound of formula (VIII), N-bromosuccinimide and palladium catalyst is 1: (1.40 ⁇ 1.60 ): (0.10 ⁇ 0.20).
  • the Claisen rearrangement reaction process includes dissolving the compound of formula (VIII), adding sodium carbonate and allyl bromide, reacting for 2.5-3.5 hours, then raising the temperature to 90-110° C. React for 1.5-2.5 hours to obtain the compound of formula (IX); wherein, the molar ratio of the compound of formula (VIII), sodium carbonate and allyl bromide is 1: (1.80-2.20): (0.80-1.20).
  • the compound of formula (VIII) and N, N-dimethylformamide (solvent) into the container in sequence, stir thoroughly for 30 minutes, and then gradually add sodium carbonate and dimethicone under the condition of sufficient stirring.
  • the dissolved solvent is one or a combination of water, tetrahydrofuran, methylene chloride, methanol, ethanol, N,N-dimethylformamide, benzene and toluene things.
  • the beneficial technical effects of the present invention are: the method of the present invention introduces the R1 substituent at the 6th position, and through the protection of the protecting group and multiple redox methods, it can be highly selective at the 5th position Introduce the R2 substituent at the 4th position, and then replace the R3 substituent at the 4th position.
  • the overall operation is convenient, does not involve anhydrous and oxygen-free operations, and the substrate is universal, while taking into account the yield.
  • the purpose of synthesizing polysubstituted 3-hydroxyl-2-pyrone was achieved.
  • Embodiment 1 a method for synthesizing multiple substituted 3-hydroxyl-2-pyrone disclosed in the present invention, comprising the following steps,
  • R 1 and R 3 are hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, carbonyl or Carboxyl; R2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, carbonyl or carboxyl.
  • Embodiment 2 A synthetic method for a polysubstituted 3-hydroxyl-2-pyrone disclosed in the present invention, the difference from Example 1 is that it includes the following steps,
  • Embodiment 3 A synthetic method for a polysubstituted 3-hydroxy-2-pyrone disclosed in the present invention, the difference from Example 1 is that it includes the following steps,
  • Embodiment 4 A synthetic method for a polysubstituted 3-hydroxyl-2-pyrone disclosed in the present invention, the difference from Example 1 is that it includes the following steps,
  • Example 5 A synthetic method for a polysubstituted 3-hydroxyl-2-pyrone disclosed in the present invention, which differs from Example 1 in that it includes the following steps,
  • the mixed solvent of 0.1mol formula (VII) compound, 0.040mol tetramethylpiperidine oxide (TEMPO), 200ml tetrahydrofuran and 20ml water was successively dropped into a 500mL three-necked flask, fully stirred for 30min, and then Cool down to -5°C, and gradually add 0.25 mol of 10% sodium hypochlorite under the condition of sufficient stirring, and react for 2.5 hours; after the reaction is completed, add saturated sodium sulfite solution to the reaction solution to quench the reaction, then extract with ethyl acetate and separate , after merging the organic phases, drying with sodium sulfate, filtering, and concentrating to obtain the compound of formula (VIII), the productive rate is as shown in Table 1.
  • TEMPO tetramethylpiperidine oxide
  • Embodiment 6 a method for synthesizing polysubstituted 3-hydroxy-2-pyrone disclosed in the present invention, the difference from Example 1 is that it includes the following steps,
  • Example 2 Example 3
  • Example 4 Example 5
  • S1 yield 98% 98% 98% 95% 94%
  • S2 yield 95% 95% 93% 95% 91%
  • S3 yield 90% 88% 92% 95% 85% S4 yield 83% 85% 88% 84%
  • S5 yield 99% 95% 99% 96% 97% S6 yield 99% 97% 95% 96% 95% S7 yield 90% 88% 83% 89% 92%
  • the method of the present invention can introduce the R2 substituent at the No. 5 position with high selectivity through protecting group protection and multiple redox methods. , and then replace the R 3 substituent at the 4th position, the overall operation is convenient, does not involve anhydrous and oxygen-free operations, and the substrate is universal, and the yield of each step is high, achieving the synthesis of multi-substituted 3- The purpose of hydroxy-2-pyrone.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé de synthèse pour une 3-hydroxy-2-pyrone polysubstituée. Le procédé comprend les étapes suivantes consistant à : S1, soumettre un composé de formule (I) à une réaction de réarrangement d'Achmatowicz pour obtenir un composé de formule (II); S2, soumettre le composé de formule (II) à une réaction de protection par un groupe de protection, une réaction de substitution, une réaction de réarrangement par oxydation, une réaction de réduction de carbonyle, une élimination de groupe de protection et une réaction d'oxydation pour obtenir le composé de formule (VIII); et S3, soumettre le composé de formule (VIII) à une réaction de couplage ou à une réaction de réarrangement de Claisen pour obtenir un composé de formule (IX). Le procédé selon la présente invention comprend l'introduction d'un substituant R1 en position 6, ce qui permet d'introduire de manière hautement sélective un substituant R2 en position 5 au moyen d'une protection par un groupe protecteur et de multiples réactions de réduction par oxydation, et ensuite un substituant R3 est substitué en position 4. L'ensemble du mode opératoire est pratique et rapide, sans impliquer des opérations telles que des opérations anhydres et anaérobies, et le substrat a une universalité, ce qui permet d'atteindre le but de synthétiser de la 3-hydroxy-2-pyrone polysubstituée avec un rendement.
PCT/CN2021/139713 2021-11-14 2021-12-20 Procédé de synthèse pour 3-hydroxy-2-pyrone polysubstituée WO2023082429A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004203783A (ja) * 2002-12-25 2004-07-22 Marine Biotechnol Inst Co Ltd 抗菌性化合物およびその製造法
WO2021211982A2 (fr) * 2020-04-17 2021-10-21 Oregon State University Synthèse régiosélective de composés substitués

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112778257A (zh) * 2021-01-21 2021-05-11 香港科技大学 一种将糠醇氧化为二氢吡喃酮类衍生物的绿色方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004203783A (ja) * 2002-12-25 2004-07-22 Marine Biotechnol Inst Co Ltd 抗菌性化合物およびその製造法
WO2021211982A2 (fr) * 2020-04-17 2021-10-21 Oregon State University Synthèse régiosélective de composés substitués

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
FITZSIMMONS B. J., PLAUMANN D. E., FRASER‐REID B.: "CHIRAL SYNTHONS FOR THE MULTISTRIATINS", CHEMISCHER INFORMATIONSDIENST, vol. 41, 1 January 1979 (1979-01-01), pages 3925 - 3928, XP093066761, ISSN: 0009-2975, DOI: 10.1002/chin.198004359 *
GILCHRIST T. L., C.W. REES: "Synthesis of 3-bromo-2-pyrones and their reactions with bases", J. CHEM. SOC. C, 1 January 1968 (1968-01-01), pages 769 - 775, XP093066753 *
ISOBE MINORU, CHANG WEI-CHUNG, TSOU PEI-KANG, PLOYSUK CHATCHAWAN, YU CHIN-HUI: "Stereochemical Course of Wittig Rearrangements of Dihydropyran Allyl Propargyl Ethers", THE JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 80, no. 12, 19 June 2015 (2015-06-19), pages 6222 - 6237, XP093066741, ISSN: 0022-3263, DOI: 10.1021/acs.joc.5b00678 *
OKADA MASAHIRO, ITO SATOKO, MATSUBARA AKIRA, IWAKURA IZUMI, EGOSHI SYUSUKE, UEDA MINORU: "Total syntheses of coronatines by exo-selective Diels–Alder reaction and their biological activities on stomatal opening", ORGANIC & BIOMOLECULAR CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, vol. 7, no. 15, 27 May 2009 (2009-05-27), pages 3065 - 3073, XP093066747, ISSN: 1477-0520, DOI: 10.1039/b905159g *
WANG JIAN, MÁRQUEZ-CADENA MIGUEL ADRIÁN, TONG RONGBIAO: "Asymmetric Total Syntheses of (+)-Penostatins A and C", ORGANIC LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 22, no. 13, 2 July 2020 (2020-07-02), US , pages 5074 - 5078, XP093066738, ISSN: 1523-7060, DOI: 10.1021/acs.orglett.0c01649 *
ZHAO ZHAIHAI, DING WANJING, WANG PIN-MEI, ZHENG DAOQIONG, XU JINZHONG: "Five polyketides isolated from the marine-derived fungus Arthrinium Sp.", NATURAL PRODUCT RESEARCH, TAYLOR AND FRANCIS HEALTH SCIENCES, ABINGDON, GB, vol. 35, no. 15, 3 August 2021 (2021-08-03), GB , pages 2470 - 2475, XP093066745, ISSN: 1478-6419, DOI: 10.1080/14786419.2019.1680663 *

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