CN107868066A - A kind of preparation method of chaff propylhomoser and its salt - Google Patents

A kind of preparation method of chaff propylhomoser and its salt Download PDF

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Publication number
CN107868066A
CN107868066A CN201710552985.2A CN201710552985A CN107868066A CN 107868066 A CN107868066 A CN 107868066A CN 201710552985 A CN201710552985 A CN 201710552985A CN 107868066 A CN107868066 A CN 107868066A
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compound
formula
salt
iii
preparation
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CN107868066B (en
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郑楠
李慧颖
李松励
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Institute of Animal Science of CAAS
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    • 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
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • 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

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

Abstract

The present invention relates to a kind of chaff propylhomoser and its preparation method of salt, including：1) formula (V) compound and alcohol are reacted to obtain formula (VI) compound；2) formula (VI) compound and 2 haloacetyl furans are reacted to obtain formula (III) compound；3) formula (III) compound obtains chaff propylhomoser or its salt through sour water solution.Wherein, R C1‑6Alkyl, R1For amino protecting group (such as tert-butoxycarbonyl Boc), X is halogen.Simply, conveniently, raw material is easy to get the method for the invention.

Description

A kind of preparation method of chaff propylhomoser and its salt
Technical field
It is more particularly to a kind of to prepare chaff propylhomoser and its method for salt the present invention relates to the preparation method of compound.
Background technology
Chaff propylhomoser (furosine, also known as furans element, structure see below formula), chemical name are that ε-N-2- furfuryls-L- relies Propylhomoserin, molecular weight are 254.28 (g/mol).Chaff propylhomoser is widely present in field of food, such as high-temperature sterilization liquid milk, infant formula Milk powder, cereal, honey and baked goods, it is the series product that Maillard reaction occurs with lactose under the high temperature conditions for lactoprotein One of, it is to judge that most accurate and important index occurs for Mei Lade early reactions.
In milk processing and detection field, furosine level and heating strength and storage in different types of dairy produce finished product It is relevant to deposit the factors such as time, it is in pasteurize milk, direct method ultrahigh-temperature instant sterilized milk, indirect method ultrahigh-temperature instant sterilized milk (UHT) content in method batch-sterilized milk, is kept to respectively may be about 0.2mg/L, 2.2mg/L, 26mg/L and 270mg/L.Therefore, in milk Control of product quality link, chaff propylhomoser concentration are commonly used for judging whether contain reconstituted milk in sterilized milk, and judge liquid milk into The quality of quality, in food processing, detection industry, the formation of chaff propylhomoser and content turn into measurement Protein in Food biology The important indicator of the extent of damage and overall nutritive value, it is significant.
At present, sterling and standard items are bought from offshore company used in chaff propylhomoser detection, and price is very expensive.In order to meet The wilderness demand of the industry of food quality inspection at present and scientific research field is, it is necessary to develop a kind of simple, practical chaff propylhomoser chemical synthesis side Method.
The content of the invention
It is an object of the invention to provide a kind of formula (I) compound and its preparation method of salt.
A kind of preparation method of formula (I) compound and its salt, including：
Wherein, R C1-6Alkyl, R1For amino protecting group (such as tert-butoxycarbonyl Boc), X is halogen；
1) formula (V) compound and alcohol are reacted to obtain formula (VI) compound；
2) formula (VI) compound and 2- haloacetyl furans are reacted to obtain formula (III) compound；
3) formula (III) compound obtains formula (I) compound or its salt through sour water solution.
According to the present invention, in the step 1), the alcohol is preferably n-butanol, tert-butyl alcohol etc.；The reaction is in DCC and 4- Reacted in the presence of dimethylamino naphthyridine.
According to the present invention, in the step 2), methods described is carried out in the basic conditions, such as sodium carbonate.
According to the present invention, in the step 3), the acid can be HCl, H2SO4Deng.
According to the present invention, the method for the step 3) includes：Formula (III) compound is subjected to amine protection reaction and obtains formula (II) compound, for example, formula (III) compound and boc- anhydride reactions are obtained into formula (II) compound；Formula (II) is changed afterwards Compound obtains formula (I) compound or its salt through sour water solution；
Wherein, R C1-6Alkyl, R1For amino protecting group (such as tert-butoxycarbonyl Boc).
The present invention also provides another method for preparing formula (I) compound or its salt, including：
Wherein, R1For amino protecting group (such as tert-butoxycarbonyl Boc), X is halogen；
I) formula (V) compound and 2- haloacetyl furans are reacted to obtain formula (III ') compound；
II) formula (III ') compound obtains formula (I) compound or its salt through sour water solution.
According to the present invention, the step I) in, methods described is carried out in the basic conditions, such as sodium carbonate.
According to the present invention, the step II) in, the acid can be HCl, H2SO4Deng.
According to the present invention, the step II) method can include：Formula (III ') compound is carried out into amine protection to react To formula (II ') compound, for example, formula (III ') compound and boc- anhydride reactions are obtained into formula (II ') compound；Afterwards, will Formula (II ') compound obtains formula (I) compound or its salt through sour water solution；
Wherein, R1For amino protecting group (such as tert-butoxycarbonyl Boc).
Simply, conveniently, raw material is easy to get the method for the invention, and can obtain the chaff propylhomoser and its salt of high-purity.
Specific embodiment
Embodiment 1
Boc-L- lysines (1 equivalent) are dissolved in isobutanol, add dicyclohexylcarbodiimide (DCC) (1.1 equivalent) With the DMAP (0.05 equivalent) of catalytic amount, reaction solution reacts 24h at room temperature, and water and second are added into reaction solution Acetoacetic ester, extraction, organic layer are washed with water three times, and anhydrous magnesium sulfate is dried, and removal of solvent under reduced pressure, obtains thick white thing.Post color Spectrum separation (eluant, eluent：Petrol ether/ethyl acetate=1/1) obtain compound (A).
Compound (A) (1 equivalent) is dissolved in DMF, sodium carbonate is added, 2- bromoacetyls furans (1 equivalent) is dissolved in DMF is simultaneously added dropwise in above-mentioned solution.Reaction is complete, adds suitable quantity of water, and Boc acid anhydrides is added dropwise, treats that compound (B) is completely converted into After compound (C), dichloromethane extraction, liquid separation are added.Dry concentration, pillar layer separation (petroleum ether：Ethyl acetate=2:1) it is dense Contracting obtains compound (C).
Compound (C) is dissolved in dioxane, the hydrogen chloride solution of dioxane is added dropwise, treats completion of dropwise addition, is stirred Reaction, until compound (C) is completely converted into compound (I)；Filter afterwards, filter cake is washed with ethyl acetate.
Embodiment 2
Boc-L- lysines (1 equivalent) are dissolved in DMF, add sodium carbonate, 2- bromoacetyls furans (1 equivalent) is molten Solution is in DMF and is added dropwise in above-mentioned solution.Reaction is complete, adds suitable quantity of water, and Boc acid anhydrides is added dropwise, and treats that compound (D) all turns Turn to compound (E).Add dichloromethane extraction, liquid separation.Dry concentration, pillar layer separation (petroleum ether：Ethyl acetate=5:1) It is concentrated to give compound (E).
Compound (E) is dissolved in appropriate dioxane, the hydrogen chloride solution of dioxane is added dropwise, waits that knot is added dropwise Beam, stirring reaction, until compound (E) is completely converted into compound (I)；Filter afterwards, filter cake is washed with ethyl acetate.

Claims (7)

1. the preparation method of a kind of formula (I) compound and its salt, including：
Wherein, R C1-6Alkyl, R1For amino protecting group (such as tert-butoxycarbonyl Boc), X is halogen；
1) formula (V) compound and alcohol are reacted to obtain formula (VI) compound；
2) formula (VI) compound and 2- haloacetyl furans are reacted to obtain formula (III) compound；
3) formula (III) compound obtains formula (I) compound or its salt through sour water solution.
2. preparation method as claimed in claim 1, wherein, in the step 1), the alcohol is preferably n-butanol, the tert-butyl alcohol Deng；The reaction is preferably reacted in the presence of DCC and DMAP.
3. preparation method as claimed in claim 1, wherein, in the step 3), the acid can be HCl, H2SO4Deng.
4. preparation method as claimed in claim 1, wherein, the step 3) includes：Formula (III) compound is subjected to amine protection Reaction obtains formula (II) compound, for example, formula (III) compound and boc- anhydride reactions are obtained into formula (II) compound；Afterwards, Formula (II) compound is obtained into formula (I) compound or its salt through sour water solution；
Wherein, R C1-6Alkyl, R1For amino protecting group (such as tert-butoxycarbonyl Boc).
5. a kind of preparation method of formula (I) compound or its salt, including：
Wherein, R1For amino protecting group (such as tert-butoxycarbonyl Boc), X is halogen；
I) formula (V) compound and 2- haloacetyl furans are reacted to obtain formula (III ') compound；
II) formula (III ') compound obtains formula (I) compound or its salt through sour water solution.
6. preparation method as claimed in claim 5, wherein, the step II) in, the acid is HCl, H2SO4Deng.
7. preparation method as claimed in claim 5, wherein, the step II) include：Formula (III ') compound is subjected to amine guarantor Shield reaction obtains formula (II ') compound, for example, formula (III ') compound and boc- anhydride reactions are obtained into formula (II ') compound； Formula (II ') compound is obtained into chaff propylhomoser or its salt through sour water solution afterwards；
Wherein, R1For amino protecting group (such as tert-butoxycarbonyl Boc).
CN201710552985.2A 2017-07-07 2017-07-07 A kind of preparation method of chaff propylhomoser and its salt Active CN107868066B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109307761A (en) * 2018-10-09 2019-02-05 华南农业大学 A kind of indirect competitive ELISA method detecting chaff propylhomoser
CN114853698A (en) * 2022-06-08 2022-08-05 深圳振强生物技术有限公司 Preparation method of furosine

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104610079A (en) * 2014-10-13 2015-05-13 湖州海创生物科技有限公司 Salbutamol hapten derivative, and artificial salbutamol antigen and preparation method and application thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104610079A (en) * 2014-10-13 2015-05-13 湖州海创生物科技有限公司 Salbutamol hapten derivative, and artificial salbutamol antigen and preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MARI´A LUZ SANZ ET AL.: "Formation of Amadori Compounds in Dehydrated Fruits", 《J. AGRIC. FOOD CHEM.》 *
杨亚军等: "2-呋喃甲酰基甲基丙氨酸的合成", 《化学试剂》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109307761A (en) * 2018-10-09 2019-02-05 华南农业大学 A kind of indirect competitive ELISA method detecting chaff propylhomoser
CN109307761B (en) * 2018-10-09 2021-06-15 华南农业大学 Indirect competitive ELISA method for detecting furaldehyde
CN114853698A (en) * 2022-06-08 2022-08-05 深圳振强生物技术有限公司 Preparation method of furosine

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