WO2010083722A1 - Procédé de synthèse monotope de la lactone de corey - Google Patents

Procédé de synthèse monotope de la lactone de corey Download PDF

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Publication number
WO2010083722A1
WO2010083722A1 PCT/CN2010/000058 CN2010000058W WO2010083722A1 WO 2010083722 A1 WO2010083722 A1 WO 2010083722A1 CN 2010000058 W CN2010000058 W CN 2010000058W WO 2010083722 A1 WO2010083722 A1 WO 2010083722A1
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WO
WIPO (PCT)
Prior art keywords
acid
reaction
formula
preparation
carboxylic acid
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Application number
PCT/CN2010/000058
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English (en)
Chinese (zh)
Inventor
孙宏斌
龚彦春
侯英伟
何广卫
Original Assignee
中国药科大学
合肥医工医药有限公司
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.)
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Publication date
Application filed by 中国药科大学, 合肥医工医药有限公司 filed Critical 中国药科大学
Publication of WO2010083722A1 publication Critical patent/WO2010083722A1/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
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
    • C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans

Definitions

  • This patent relates to a method for synthesizing Corey lactone, a key intermediate in the total synthesis of prostaglandins. Background technique ,
  • Prostaglandins are an important endogenous physiologically active natural product, which is extremely low in biological tissues. It was discovered by von Enler in 1930, and its skeleton is composed of a five-membered ring.
  • the carboxylic acid of 20 carbon atoms according to the structural difference of the five-membered ring, the natural prostate can be of the PGA, PGB, PGC, PGE and PGF types, prostaglandins on the reproductive system, nervous system, respiratory system, endocrine and other systems. has an effect.
  • PGE 2 the drug for the induction of labor
  • PGE dinoprostone
  • glaucoma treatments such as Travoprost and Latanoprost.
  • Corey lactone acid of formula II 5-hydroxy-hexahydro-2-oxo-277-cyclopenta[b]furan-4-carboxylic acid, the molecular formula is: C 8 H 1() 0 5 , the molecular weight is 186.05.
  • the racemate of Corey lactone is resolved by S-((x)-phenethylamine (Liu Zhizhen et al., Organic Chemistry, 1985, 371-372), which readily forms an anti-imiding salt, is easily crystallized, and can be non- The same amount of salt, more economical when split, the free optical pure (-)-Corey lactone acid can be used to synthesize various prostaglandins (PGs).
  • the Corey lactone acid represented by the formula II is mainly obtained by oxidation reaction of 2-halo-5-oxobicyclo[2.2.1]heptane-7-carboxylic acid represented by the formula I and an ester derivative thereof. 6-Chloro- 3- oxo-2-oxabicyclo[3.2.1]octane-8-carboxylic acid and its ester derivative are shown in hydrazine, and then hydrolyzed by ring opening and cyclized.
  • the main difference between the existing Corey lactone acid preparation methods is that the oxidizing agent used in the first oxidation reaction is different, and can be roughly classified into the following two categories:
  • the oxidation reaction has a single step yield of 70%;
  • step-by-step synthesis 3 steps can be completed using 2 or even 3 reaction vessels.
  • the synthesis of Corey lactone acid, the separation and purification of each step is troublesome;
  • M-chloroperoxybenzoic acid and peracetic acid are easy to release oxygen. It is unsafe to store and transport. The higher the purity, the greater the risk, especially the high concentration of peracetic acid, which is extremely explosive;
  • the object of the present invention is to overcome the deficiencies of the above-mentioned techniques and to provide a novel process for synthesizing Corey lactone acid by a one-pot method.
  • the present invention uses a potassium persulfate preparation (OXONE) as an oxidant, and the one-pot process for preparing the Corey lactone acid of the formula II includes the following steps:
  • the method for preparing a compound of formula III using the potassium peroxodisulfate formulation (OXONE) as an oxidizing agent comprises the following steps:
  • the compound of the formula III can be obtained by a conventional method of treatment and purification. Compared with the prior art, the advantages of the invention are as follows:
  • the oxidizing agent potassium persulfate preparation (OXO E) used in the new process described in the present invention is one-tenth the price of m-chloroperoxybenzoic acid, so that the production cost can be greatly reduced;
  • Figure 1 shows dinoprostone (PGE 2 ), alprostadil (PGE ⁇ travoprost) (Travoprost) and the structure of Latanoprost;
  • Figure 2 shows the 2-chloro-5-oxobicyclo[2.2.1]heptane-7-carboxylic acid of formula I and its ester derivative obtained by oxidation to give 6-chloro- represented by formula III.
  • the structure of the compound prepared by the method of the present invention has been confirmed by hydrogen spectrum, carbon spectrum and mass spectrometry, and the structure is correct.
  • Corey lactone is the same term as Corey lactone acid.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un procédé de synthèse monotope de la lactone de Corey, caractérisé en ce qu'il comprend la sélection de l'acide 2-halogéno-5-oxobicyclo[2.2.1]heptane-7-carboxylique et ses dérivés ester de formule I en tant matière première, l'ajout d'un oxydant, une alcalinisation avec une base, une acidification avec un acide, la terminaison de l'oxydation du matériau, une ouverture de cycle, une cyclisation en continu dans le même réacteur, et une purification pour obtenir l'acide 5-hydroxy-hexahydro-2-oxo-2H-cyclopenta[b]furane-4-carboxylique de formule II, c.-à-d. la lactone de Corey. Selon le procédé de synthèse monotope de la lactone de Corey de formule II, la lactone de Corey est facile à séparer et est l'intermédiaire clé pour la synthèse de prostaglandines. Le procédé est simple à mettre en œuvre et les matières premières sont peu coûteuses et faciles à obtenir. Le procédé ne pollue pas l'environnement et peut réduire le coût de production de la lactone de Corey dans une large mesure.
PCT/CN2010/000058 2009-01-20 2010-01-13 Procédé de synthèse monotope de la lactone de corey WO2010083722A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200910028164.4A CN101525322B (zh) 2009-01-20 2009-01-20 一锅煮方法合成Corey内酯的新工艺
CN200910028164.4 2009-01-20

Publications (1)

Publication Number Publication Date
WO2010083722A1 true WO2010083722A1 (fr) 2010-07-29

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PCT/CN2010/000058 WO2010083722A1 (fr) 2009-01-20 2010-01-13 Procédé de synthèse monotope de la lactone de corey

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CN (1) CN101525322B (fr)
WO (1) WO2010083722A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112680497A (zh) * 2020-12-31 2021-04-20 南京赛信生物科技有限公司 生物酶拆分前列腺素类药物关键中间体（1S,5R）-Corey内酯的方法

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101525322B (zh) * 2009-01-20 2014-04-16 中国药科大学 一锅煮方法合成Corey内酯的新工艺
CN102206224B (zh) * 2011-03-23 2013-06-26 北京洛斯顿精细化工有限公司 制备（1aR,2aS,5aS,5bS）-四氢-1aH-环氧[2’,3’:3,4]环戊烷并[1,2-b]呋喃-4(5bH)-酮的方法
CN108993354A (zh) * 2018-07-03 2018-12-14 南京拉艾夫医药科技有限公司 一种Corey内酯的合成装置及合成工艺
CN110078613B (zh) * 2019-05-31 2022-04-22 杭州科耀医药科技有限公司 一种2-卤-5-碘苯甲酸的合成方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3952019A (en) * 1973-05-15 1976-04-20 Imperial Chemical Industries Limited Bicyclo-octane derivatives
US3992438A (en) * 1973-10-24 1976-11-16 Pfizer Inc. Novel prostaglandin intermediates
CS216027B1 (cs) * 1980-11-27 1982-10-29 Ivan Stibor Způsob výroby (3a</ ,4 β,5ιΧ ,6β0<)hexahydro-5-acyloxy-4-karboxy-2H-cyklcpent9[V]furan- -2-onu
CN101525322A (zh) * 2009-01-20 2009-09-09 中国药科大学 一锅煮方法合成Corey内酯的新工艺

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7511168B2 (en) * 2006-01-18 2009-03-31 Shih-Yi Wei Processes and intermediates for the preparations of prostaglandins

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3952019A (en) * 1973-05-15 1976-04-20 Imperial Chemical Industries Limited Bicyclo-octane derivatives
US3992438A (en) * 1973-10-24 1976-11-16 Pfizer Inc. Novel prostaglandin intermediates
CS216027B1 (cs) * 1980-11-27 1982-10-29 Ivan Stibor Způsob výroby (3a</ ,4 β,5ιΧ ,6β0<)hexahydro-5-acyloxy-4-karboxy-2H-cyklcpent9[V]furan- -2-onu
CN101525322A (zh) * 2009-01-20 2009-09-09 中国药科大学 一锅煮方法合成Corey内酯的新工艺

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112680497A (zh) * 2020-12-31 2021-04-20 南京赛信生物科技有限公司 生物酶拆分前列腺素类药物关键中间体（1S,5R）-Corey内酯的方法

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CN101525322B (zh) 2014-04-16
CN101525322A (zh) 2009-09-09

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