WO1997019949A1 - Derives d'acide ascorbique et leur preparation - Google Patents

Derives d'acide ascorbique et leur preparation Download PDF

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Publication number
WO1997019949A1
WO1997019949A1 PCT/CN1996/000105 CN9600105W WO9719949A1 WO 1997019949 A1 WO1997019949 A1 WO 1997019949A1 CN 9600105 W CN9600105 W CN 9600105W WO 9719949 A1 WO9719949 A1 WO 9719949A1
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WO
WIPO (PCT)
Prior art keywords
ascorbic acid
acceptable salt
physiologically acceptable
acid
acid derivative
Prior art date
Application number
PCT/CN1996/000105
Other languages
English (en)
Chinese (zh)
Inventor
Xiongfei Zeng
Jianya Cai
Original Assignee
Beijing Chaobai River New Technology Research Institute
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 Beijing Chaobai River New Technology Research Institute filed Critical Beijing Chaobai River New Technology Research Institute
Publication of WO1997019949A1 publication Critical patent/WO1997019949A1/fr

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Classifications

    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/94—Bismuth compounds
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/66—Arsenic compounds
    • C07F9/70—Organo-arsenic compounds
    • C07F9/80—Heterocyclic compounds
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/90—Antimony compounds

Definitions

  • the present invention relates to new ascorbic acid derivatives. More specifically, the present invention relates to a new class of ascorbic acid derivatives obtained by esterification at the c 3 position of ascorbic acid and introducing oxygen-containing acid groups of nitrogen elements The invention also relates to a preparation method of the ascorbic acid derivative and its application in feed, health products and medicine.
  • Ascorbic acid or vitamin C is one of the most important vitamins in animals. It is involved in the hydroxylation of collagen, nerve media, hormones and steroids, as well as the redox reaction, and has very important biological effects. But it is easily oxidized and hydrolyzed, thus Loss of its biological activity; Humans and aquatic animals cannot synthesize by themselves, and the supplementation of exogenous sources further exacerbates the deficiency of vitamin C. Seeking a stable source of vitamin C is a long-term goal of scientists. The use of envelope processing and synthesis of its derivatives There are two main pathways. The stabilization effect of the coating treatment is very small.
  • the compound has good thermal stability It also has good biological activity.
  • the formed hydrogen bond structure makes ascorbic acid easy to hydrolyze, has a reduced content of vitamin C ester with biological activity, L-ascorbic acid has a low titer, high by-products, and the biological effects of triphosphates cannot be exerted.
  • the function and application of an invention are greatly limited.
  • the purpose of the present invention is to overcome the shortcomings of the background art, design a structure that does not destroy the hydroxy group on the two carbons to form an association bond with one carbonyl group, perform esterification on the three carbons, and introduce a group containing a nitrogen group element Ascorbic acid derivatives that improve stability and increase biological activity.
  • the present invention relates to an ascorbic acid derivative having the following general formula I and a physiologically acceptable replacement page thereof (Detailed Article 26) salt:
  • z represents an oxo acid group of a nitrogen group element.
  • Esterification of ascorbic acid on C 3 protects the associative ring formed by ( ⁇ and (: 2) , thereby improving the comprehensive stability and biological function of ascorbic acid to water, light and heat.
  • L-ascorbic acid on its C 3 After tripolyphosphate esterification, the effect is more obvious.
  • L-ascorbic acid 3-tripolyphosphate has a comprehensive stability more than 10 times that of L-ascorbic acid. Its lactone is difficult to hydrolyze, and its potency is increased by more than three times. Less product.
  • the proton (H +) can protect the hydroxyl group on the second carbon, the proton can be provided by inorganic or organic acid.
  • the hydroxyl on the third carbon of ascorbic acid is the same as the phosphorus and arsenic in the nitrogen , Antimony, bismuth-containing oxo acid, esterification reaction occurs, so as to obtain stable and highly active ascorbic acid ⁇ "organism.
  • Z represents an oxo acid group of a nitrogen group element, preferably
  • the preferred alkali metals are metals such as sodium and potassium.
  • the preferred alkaline earth metals are metals such as calcium and magnesium.
  • the most preferred group of compounds of the present invention is L-ascorbic acid 3-tripolyphosphate sodium salt, L-ascorbic acid 3-tripolyphosphate potassium salt, L-ascorbic acid 3-arsenite, L-ascorbic acid 3-partial Arsenite, L -ascorbic acid 3 -metaantimonate, L -ascorbic acid 3 -metabismuthate.
  • the method for synthesizing the ascorbic acid derivative of the present invention includes esterifying an ascorbic acid with an oxo acid of a nitrogen group element in an aqueous solvent under acidic conditions.
  • the concentration ratio of the ascorbic acid to the oxo acid is 1: 1 to 3.
  • the temperature is 25-80 'C, preferably 45-75,: 4 is preferably 50-70, and the pH is between 2.0 and 6.5, preferably 4.5-5.5, and the reaction time is 2-10 hours,
  • the pH adjusting agent used in the synthesis method of the present invention includes inorganic acids and / or organic acids, without 3 ⁇ 43 ⁇ 4 and / or ⁇ 3 ⁇ 4,
  • inorganic acids examples include hydrochloric acid, sulfuric acid, phosphoric acid, boric acid, etc.
  • organic acids examples include formic acid, acetic acid, propionic acid, butyric acid, oxalic acid, lactic acid, fumaric acid, malic acid, etc.
  • inorganic bases include caustic, carbon Examples of acid salts, reducing oxides, organic bases such as pyridine.
  • ONa ONa replacement page (Article 26) Add 50ml of water to a 150ml glass reactor with an electromagnetic stirrer inserted into a glass pH electrode, and heat to 50-55 in a water bath. Weigh 30g of L-ascorbic acid and 52g of sodium tripolyphosphate in total. Under a nitrogen atmosphere and Under stirring conditions, first add 10 g of L-ascorbic acid, 2 ml of 38% concentrated hydrochloric acid, and then add 20 g of sodium trimerate, and the remaining L-ascorbic acid and sodium trimerate are added in equal amounts of 5 times.
  • reaction product was concentrated and dried under vacuum to obtain a light yellow solid powder. Take out 1/5 of the product, add an appropriate amount of water to dissolve it, and purify it by a liquid chromatography column. Dry to get white powder.
  • the reaction device and method are similar to Example 1, except that arsenite is used instead of sodium tripolyphosphate.
  • the total amount of arsenite added is 18g.
  • the comprehensive analysis of organic wave language proves that ⁇
  • the organism is L-ascorbic acid 3-arsenite.
  • the 0 z reaction apparatus and method are similar to those in Example 5, except that meta-bismuth acid is used instead of meta-antimony acid.
  • the total amount of meta-bismuth and acid added is 34 g.
  • the purified product was subjected to elemental analysis and organic Spectral detection proved to be L-ascorbic acid 3-bis-bismuthite, an ester.
  • the test and control groups were set up with aerators.
  • the test group was fed L-ascorbic acid 3- Trimeric acid esters, the control group were fed with the same potency of L-ascorbic acid and L-ascorbic acid 2-tripolyphosphate (ultraviolet absorption maximum 258nm).
  • the respiration rate of carps decreased by 20-30% for 14 hours, but all the control groups had no such effect, and the respiration rate increased instead.
  • Anti-hypoxia and anti-stress performance is significant.
  • the ascorbic acid juice organisms of the present invention are added to carp, grass carp, prawn, eel and other bait to increase yield and increase feed compensation by more than 8%.
  • the L-ascorbic acid 3-arsenite of the present invention is added to the shrimp bait to feed the prawn, which significantly improves the health and disease resistance of the shrimp.
  • the L-ascorbic acid derivative according to the present invention can be esterified on three carbons, and can also be other forms of polyacid, arsenic acid, antimony acid, bismuth acid, or their salts.
  • the organic acid can also be flax. Acid, citric acid, niacin, folic acid, etc. can also make this series of L-ascorbic acid derivatives form the corresponding alkali metal, alkaline earth metal salts.
  • the L-ascorbic acid 3-polygallate is used as a new source of vitamin C and has been applied in aquaculture.
  • the invention opens up a new way for ascorbic acid in the breeding industry, food industry and animal and plant disease control.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Fodder In General (AREA)
  • Furan Compounds (AREA)

Abstract

La présente invention décrit un type de nouveaux dérivés d'acide ascorbique présentant les caractéristiques de l'estérification en C3 et l'introduction de groupes oxy-acides contenant P, As, Sb et Bi. Ainsi on améliore leurs propriétés physiques et chimiques et on augmente la stabilité totale contre l'eau, la chaleur et la lumière ainsi que l'activité physiologique. On utilise les composés de la présente invention en agriculture, dans l'industrie alimentaire ainsi que contre les maladies affectant les plantes et les animaux.
PCT/CN1996/000105 1995-11-28 1996-11-27 Derives d'acide ascorbique et leur preparation WO1997019949A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN95118385A CN1208041A (zh) 1995-11-28 1995-11-28 抗坏血酸衍生物
CN95118385.0 1995-11-28

Publications (1)

Publication Number Publication Date
WO1997019949A1 true WO1997019949A1 (fr) 1997-06-05

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Application Number Title Priority Date Filing Date
PCT/CN1996/000105 WO1997019949A1 (fr) 1995-11-28 1996-11-27 Derives d'acide ascorbique et leur preparation

Country Status (2)

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CN (1) CN1208041A (fr)
WO (1) WO1997019949A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998030555A1 (fr) * 1997-01-14 1998-07-16 Sakalosky George P Traitement du cancer et composes utilises dans ce traitement
EP2637674A1 (fr) * 2010-11-08 2013-09-18 Synthonics, Inc. Composés contenant du bismuth pour moduler les propriétés d'agents biologiquement actifs

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103554070A (zh) * 2013-11-08 2014-02-05 李玉成 抗坏血酸氧铋、其制备方法及应用
CN105330701B (zh) * 2015-11-27 2017-05-31 昆明医科大学 一种含砷化合物及其制备方法和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3671549A (en) * 1970-03-05 1972-06-20 Merck & Co Inc Process for preparing ascorbyl-3-phosphate and salts thereof
US4647672A (en) * 1985-06-25 1987-03-03 Kansas State University Research Foundation Ascorbate 2-polyphosphate esters and method of making same

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3671549A (en) * 1970-03-05 1972-06-20 Merck & Co Inc Process for preparing ascorbyl-3-phosphate and salts thereof
US4647672A (en) * 1985-06-25 1987-03-03 Kansas State University Research Foundation Ascorbate 2-polyphosphate esters and method of making same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 124:54473d; & J. NUTR., 1995, 125(12), pages 3055-3061. *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998030555A1 (fr) * 1997-01-14 1998-07-16 Sakalosky George P Traitement du cancer et composes utilises dans ce traitement
US6294678B1 (en) 1997-01-14 2001-09-25 George P. Sakalosky Treatment for cancer and compounds for use therewith
EP2637674A1 (fr) * 2010-11-08 2013-09-18 Synthonics, Inc. Composés contenant du bismuth pour moduler les propriétés d'agents biologiquement actifs
JP2013542961A (ja) * 2010-11-08 2013-11-28 シンソニックス、インク． 生理活性物質の性質を調節するビスマス含有化合物
EP2637674A4 (fr) * 2010-11-08 2014-11-26 Synthonics Inc Composés contenant du bismuth pour moduler les propriétés d'agents biologiquement actifs
JP2017101029A (ja) * 2010-11-08 2017-06-08 シンソニックス、インク． 生理活性物質の性質を調節するビスマス含有化合物
US10150792B2 (en) 2010-11-08 2018-12-11 Synthonics, Inc. Bismuth-containing compounds, coordination polymers, methods for modulating pharmacokinetic properties of biologically active agents, and methods for treating patients

Also Published As

Publication number Publication date
CN1208041A (zh) 1999-02-17

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