CN108047177A - The method of one-step synthesis benzofurans β-dehydrogenation alpha-non-natural amino acid - Google Patents
The method of one-step synthesis benzofurans β-dehydrogenation alpha-non-natural amino acid Download PDFInfo
- Publication number
- CN108047177A CN108047177A CN201711376129.2A CN201711376129A CN108047177A CN 108047177 A CN108047177 A CN 108047177A CN 201711376129 A CN201711376129 A CN 201711376129A CN 108047177 A CN108047177 A CN 108047177A
- Authority
- CN
- China
- Prior art keywords
- benzofurans
- natural amino
- amino acid
- dehydrogenation
- methyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
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
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
Abstract
The invention discloses the methods of one-step synthesis benzofurans β dehydrogenation alpha-non-natural amino acids, make benzene oxanamide class compound with bromo propiolate in organic solvent environment, catalytic reaction obtains 2 amino, the benzofurans β dehydrogenation non-natural amino acid compounds of 3 carboxyls substitution.The raw material used in this method is cheap and easy to get, and reaction can carry out at ambient temperature and processing procedure is simple, makes it easier to operation and large-scale production.Waste gas and wastes are nearly free from reaction process, environmentally protective Atom economy is high.By this method, 2 amino of one-step synthesis, the benzofurans β dehydrogenation non-natural amino acid compounds of 3 carboxyls substitution provide new thinking for molecular biology research for the first time.
Description
Technical field
The present invention relates to technical field of organic synthesis, are related to one-step synthesis benzofurans β-dehydrogenation alpha-non-natural amino acid
Method.
Background technology
It is known that protein all in organism is made of 20 kinds of natural amino acids, amino acid is namely to albumen
Quality Research basic tool and optimal point of penetration, scientists are by the arrangement to Amino Acids in Proteins and functional group come between
Precision architecture, action target spot and the mechanism of action of research protein are connect, and further seeks to realize the artificial reparation to protein
And transformation.However the functional group limited amount that only 20 kinds of natural amino acids carry, chemistry can not be met, bioscience is ground
To the demand of protein structure and function in studying carefully and applying.Then pass through artificial means synthesis it is a variety of have the function of different groups and
Alpha-non-natural amino acid become the important means of molecular biology research, wherein β-dehydrogenation alpha-non-natural amino acid be a kind of application compared with
More alpha-non-natural amino acids.Benzofuran compounds exist in many natural plants, and with multiple biological activities.Its
In some substituted benzene well furfuran compounds, have good antitumor, antiviral, antimycotic, anti-oxidant, immunosupress etc. raw
Reason activity.Since such separated compound is limited from natural products, the heat constructed as organic synthesis of the structure
One of point.
With reference to the research application advantage of alpha-non-natural amino acid and the physiological activity feature of benzofuran compounds, benzene is synthesized
Benzofuran alpha-non-natural amino acid.It will be with important application prospect in molecular biology research.It has reported and has developed at present
The method of synthesis benzofuran compounds is concentrated mainly on by transition metal-catalyzed intramolecular or the conjunction of intermolecular coupling reaction
Into the benzofuran compounds of 2- or 2,3- substitutions, the substituent group of these 2- and 3- is typically limited to part aryl
And alkyl.And benzofurans alpha-non-natural amino acid, i.e., 2, the 3- benzofuran derivatives that respectively amino and carboxyl substitute
Chemical synthesis it is also relatively difficult be rarely reported, therefore relevant biological study also compares limitation.
The starting material that the method for existing synthesis benzofuran derivative is used at present need to usually carry out function in advance
Change, some reaction substrates are even more complicated and are difficult to obtain；It needs to use expensive metallic catalyst in reaction process and lead to
Often need higher thermotonus condition harsher；The benzofuran compounds species of synthesis is limited, it is impossible to obtain simultaneously
There are amino and the benzofuran of carboxyl substitution.(Furstner,A.and Davies,P.W..J.Am.Chem.Soc.,2005,
127,15024.)
The content of the invention
First problem to be solved by this invention is the drawbacks described above for overcoming the prior art, provides a kind of mild condition,
Post processing is simple, is suitble to the method for one-step synthesis benzofurans β-dehydrogenation alpha-non-natural amino acid of industrialized production.
In order to solve the above technical problems, technical solution provided by the invention is:One-step synthesis benzofurans β-dehydrogenation is non-
The method of natural amino acid, includes the following steps：Benzene oxanamide class compound (formula 1) is having with bromo propiolate (formula 2)
In solvent environment, catalytic reaction obtains 2- amino, benzofurans β-dehydrogenation alpha-non-natural amino acid chemical combination of 3- carboxyls substitution
Object (formula 3)；
Wherein,R=4- methyl, 4- ethyls, 4- isopropyls, 6- methyl, 6- ethyls, 3,5- dimethyl,
4- fluorine, 4- chlorine, the chloro- 6- methyl of 4-, 5- methyl, 3- methyl, 5- bromines, 3- bromines,
4-The chloro- 6- of 3-
R1=methyl, ethyl, isopropyl, tert-butoxy；
R2=-COOEt ,-COOMe.
In currently preferred technical solution, above-mentioned reaction system carries out under the catalytic action of sodium methoxide.
In currently preferred technical solution, above-mentioned reaction system carries out in ethyl acetate solvent, i.e., described organic
Solvent is ethyl acetate.
In currently preferred technical solution, the amount of sodium methoxide is 2 times of the amount of benzene oxanamide class combinations of materials.
In currently preferred technical solution, the amount for adding in bromo propiolate is the amount of benzene oxanamide class combinations of materials
2 times.
In currently preferred technical solution, above-mentioned reaction carries out at normal temperatures and pressures.
In reaction method of the present invention, 10ml ethyl acetate (EA) is added in per 1mmol raw materials as solvent, reaction time 6-
12 it is small when.
The 2- amino of 22 kinds of different substitutions, benzofurans β-non-day of dehydrogenation of 3- carboxyls substitution have been synthesized by this method
Right amino-acid compound, it is as shown in table 1 below：Letter wherein below each compound is its class mark, and percentage figures are
Yield:
Table 1
After the phenol of difference substitution obtains benzene oxanamide class compound by known method, under the action of sodium methoxide,
2- amino can efficiently be obtained by being reacted at ambient temperature with bromo propiolate in ethyl acetate solvent, the substitution of 3- carboxyls
Benzofurans β-dehydrogenation non-natural amino acid compound.A variety of benzofurans β-dehydrogenations by this method one-step synthesis
Non-natural amino acid compound.
The condition of reaction is to be dissolved in 1mmol benzene oxanamide substrates and 2mmol sodium methoxides in 10ml second ethyl acetate solvents,
2mmol bromo propiolates are added, a variety of 2- amino are can obtain after reacting 6-12h under room temperature, the substitution of 3- carboxyls
Benzofurans β-dehydrogenation non-natural amino acid compound；
This method is from the synthesis 2- amino of starting material simple and easy to get, in a mild condition economical and efficient, 3- carboxylics
Benzofurans β-dehydrogenation non-natural amino acid compound of base substitution.Benzene oxanamide class chemical combination is obtained by one step of raw material of phenol
Its step that reacts at ambient temperature with bromo propiolate of object obtains 2- amino, and the benzofurans β of 3- carboxyls substitution-
Dehydrogenation non-natural amino acid compound.It only needs to add in a certain amount of sodium methoxide in reaction, reaction yield is high, adaptability is good.It crosses
It only produces a small amount of sodium bromide in journey to generate almost without other by-products, Atom economy height meets the reason of Green Chemistry
It reads.
The raw material used in this method is cheap and easy to get, and reaction can carry out at ambient temperature and processing procedure is simple, makes
Its easily operated and large-scale production.Waste gas and wastes are nearly free from reaction process, environmentally protective Atom economy is high.Pass through
One-step synthesis 2- amino, benzofurans β-dehydrogenation non-natural amino acid compound of 3- carboxyls substitution are this method for the first time
Molecular biology research provides new thinking.
Specific embodiment
In order to make it easy to understand, the present invention will be described in detail by specific embodiment below.It needs to refer in particular to
Go out, the description that these descriptions are merely exemplary, and be not meant to limit the scope of the invention.Opinion according to this specification
It states, many variations of the invention, change will be apparent from for one of ordinary skill in the art.
Embodiment 1
1mmol benzene oxanamide substrates (phenoxy acetamide) and 2mmol sodium methoxides is taken to be dissolved in 10ml ethyl acetate solvents, then
2mmol bromos propiolate (3- propargyl bromides acetoacetic ester) is added in, 2- amino, 3- are can obtain after reacting 6-12h under room temperature
Benzofurans β-dehydrogenation non-natural amino acid compound (2- acetylaminohydroxyphenylarsonic acid 3- Ethyl formate benzofurans of carboxyl substitution
4a), 0.92mmol, yield 92%.
Embodiment 2
Take 1mmol benzene oxanamides substrate (4- methylenedioxy phenoxies acetamide) and 2mmol sodium methoxides to be dissolved in 10ml ethyl acetate molten
In agent, 2mmol bromos propiolate (3- propargyl bromides acetoacetic ester) is added, 2- is can obtain after reacting 6-12h under room temperature
Amino, benzofurans β-dehydrogenation non-natural amino acid compound (5- methyl -2- acetylaminohydroxyphenylarsonic acid 3- formic acid of 3- carboxyls substitution
Ethyl ester benzofuran 4b), 0.87mmol, yield 87%.
Embodiment 3
Take 1mmol benzene oxanamides substrate (4- ethyls phenoxy acetamide) and 2mmol sodium methoxides to be dissolved in 10ml ethyl acetate molten
In agent, 2mmol bromos propiolate (3- propargyl bromides acetoacetic ester) is added, 2- is can obtain after reacting 6-12h under room temperature
Amino, benzofurans β-dehydrogenation non-natural amino acid compound (5- ethyl -2- acetylaminohydroxyphenylarsonic acid 3- formic acid of 3- carboxyls substitution
Ethyl ester benzofuran 4c), 0.75mmol, yield 75%.
Embodiment 4
1mmol benzene oxanamides substrate (benzene oxygen propionamide) and 2mmol sodium methoxides is taken to be dissolved in 10ml ethyl acetate solvents, then
2mmol bromos propiolate (3- propargyl bromides acetoacetic ester) is added in, 2- amino, 3- are can obtain after reacting 6-12h under room temperature
Benzofurans β-dehydrogenation non-natural amino acid compound (2- propionamido -3- Ethyl formate benzofurans of carboxyl substitution
4m), 0.88mmol, yield 88%.
Embodiment 5
Take 1mmol benzene oxanamides substrate (4- methylenedioxy phenoxies acetamide) and 2mmol sodium methoxides to be dissolved in 10ml ethyl acetate molten
In agent, 2mmol bromos propiolate (3- propargyl bromide acid methyl esters) is added, 2- is can obtain after reacting 6-12h under room temperature
Amino, benzofurans β-dehydrogenation non-natural amino acid compound (5- methyl -2- acetylaminohydroxyphenylarsonic acid 3- formic acid of 3- carboxyls substitution
Methyl esters benzofuran 4s), 0.92mmol, yield 92%.
The foregoing examples are merely illustrative of the technical concept and features of the invention, its object is to allow the person skilled in the art to be
Present disclosure can be understood and implemented according to this, it is not intended to limit the scope of the present invention.It is all smart according to the present invention
The equivalent transformation or modification that refreshing essence is done, should be covered by the protection scope of the present invention.
Claims (6)
1. the method for one-step synthesis benzofurans β-dehydrogenation alpha-non-natural amino acid, which is characterized in that benzene oxanamide class compound
With bromo propiolate in organic solvent environment, catalytic reaction obtains 2- amino, the benzofurans β that 3- carboxyls substitute-de-
Hydrogen non-natural amino acid compound；
Wherein, R=4- methyl, 4- ethyls, 4- isopropyls, 6- methyl, 6- ethyls, 3,5- dimethyl, 4- fluorine, 4- chlorine, the chloro- 6- of 4-
Methyl, 5- methyl, 3- methyl, 5- bromines, 3- bromines,
4-The chloro- 6- of 3-
R1=methyl, ethyl, isopropyl, tert-butoxy；
R2=-COOEt ,-COOMe.
2. synthetic method according to claim 1, which is characterized in that above-mentioned reaction system is in the catalytic action of sodium methoxide
Lower progress.
3. synthetic method according to claim 1, which is characterized in that above-mentioned reaction system in ethyl acetate solvent into
Row.
4. synthetic method according to claim 2, which is characterized in that the amount of sodium methoxide is benzene oxanamide class combinations of materials
2 times of amount.
5. synthetic method according to claim 1, which is characterized in that the amount for adding in bromo propiolate is benzene oxanamide class
2 times of the amount of combinations of materials.
6. synthetic method according to claim 1, which is characterized in that above-mentioned reaction carries out at normal temperatures and pressures.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711376129.2A CN108047177B (en) | 2017-12-19 | 2017-12-19 | Method for synthesizing benzofuran beta-dehydrogenation unnatural amino acid in one step |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711376129.2A CN108047177B (en) | 2017-12-19 | 2017-12-19 | Method for synthesizing benzofuran beta-dehydrogenation unnatural amino acid in one step |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108047177A true CN108047177A (en) | 2018-05-18 |
| CN108047177B CN108047177B (en) | 2021-05-11 |
Family
ID=62130052
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711376129.2A Active CN108047177B (en) | 2017-12-19 | 2017-12-19 | Method for synthesizing benzofuran beta-dehydrogenation unnatural amino acid in one step |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108047177B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108752299A (en) * | 2018-07-18 | 2018-11-06 | 青岛科技大学 | A kind of preparation method of 3- benzofuranones |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101747302A (en) * | 2008-12-05 | 2010-06-23 | 中国人民大学 | Method for synthesizing polysubstituted benzofuran compounds |
| CN103275043A (en) * | 2013-06-09 | 2013-09-04 | 中国科学院成都生物研究所 | Synthesis method for 2-arylbenzofuran and derivative thereof |
| CN105669618A (en) * | 2016-01-07 | 2016-06-15 | 上海应用技术学院 | Preparation method of polysubstituted benzofuran derivative |
-
2017
- 2017-12-19 CN CN201711376129.2A patent/CN108047177B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101747302A (en) * | 2008-12-05 | 2010-06-23 | 中国人民大学 | Method for synthesizing polysubstituted benzofuran compounds |
| CN103275043A (en) * | 2013-06-09 | 2013-09-04 | 中国科学院成都生物研究所 | Synthesis method for 2-arylbenzofuran and derivative thereof |
| CN105669618A (en) * | 2016-01-07 | 2016-06-15 | 上海应用技术学院 | Preparation method of polysubstituted benzofuran derivative |
Non-Patent Citations (5)
| Title |
|---|
| GUIXIA LIU 等: "Rhodium(III)‐Catalyzed Redox‐Neutral Coupling of N‐Phenoxyacetamides and Alkynes with Tunable Selectivity", 《ANGEW. CHEM. INT. ED.》 * |
| OKIKO MIYATA 等: "Highly Effective Synthetic Methods for Substituted 2-Arylbenzofurans Using [3,3]-Sigmatropic Rearrangement: Short Syntheses of Stemofuran A and Eupomatenoid 6", 《ORGANIC LETTERS》 * |
| TAKEDA, NORIHIKO: "Selective synthesis of benzofurans and dihydrobenzofurans via efficient rearrangement as key reaction", 《YAKUGAKU ZASSHI》 * |
| ZHI ZHOU 等: "Synthesis of benzofurans via ruthenium-catalyzed redox-neutral C–H functionalization and reaction with alkynes under mild conditions", 《ORG. CHEM. FRONT.》 * |
| 燕鼎元: "基于N-苯氧酰胺的[i，3]-重排反应构建生物活性骨架分子（i=2，3）", 《中国博士学位论文全文数据库 工程科技Ⅰ辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108752299A (en) * | 2018-07-18 | 2018-11-06 | 青岛科技大学 | A kind of preparation method of 3- benzofuranones |
| CN108752299B (en) * | 2018-07-18 | 2019-09-27 | 青岛科技大学 | A kind of preparation method of 3- benzofuranones |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108047177B (en) | 2021-05-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108912171B (en) | Synthesis method of 4-dimethylaminobenzoyl diphenylphosphine or 4-di-n-hexylaminobenzoyl diphenylphosphine | |
| Yadav et al. | Iron-Catalyzed Oxidative Sulfonylation of Enol Acetates: An Environmentally Benign Approach to β-Keto Sulfones | |
| US7754889B2 (en) | Optically active transition metal-diamine compound and process for producing optically active alcohol with the same | |
| Bartoli et al. | The CeCl3· 7H2O–NaI system as promoter in the synthesis of functionalized trisubstituted alkenes via Knoevenagel condensation | |
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| CN111153869B (en) | Method for preparing oxazole compound | |
| Yuan et al. | Catalytic asymmetric aromatizing inverse electron-demand [4+ 2] cycloaddition of 1-thioaurones and 1-azaaurones | |
| CN108047177A (en) | The method of one-step synthesis benzofurans β-dehydrogenation alpha-non-natural amino acid | |
| CN105440012A (en) | Lenalidomide and lenalidomide intermediate preparation method | |
| Yu et al. | Rhodium-catalyzed asymmetric 1, 4-addition of heteroaryl cyclic triolborate to α, β-unsaturated carbonyl compounds | |
| CN105061375B (en) | Method for preparing 3-isochromanone | |
| CN110240554B (en) | Alpha-thioether aryl acetonitrile compound and synthetic method thereof | |
| KR20220085758A (en) | Method for the synthesis of 2,5-furandicarboxylic acid | |
| CN114702425A (en) | Preparation method of (S) -2-amino- (S) -3- [ pyrrolidone-2' ] alanine derivative and intermediate | |
| CN109942433B (en) | Chemical synthesis method of 3',4',5' -trifluoro-2-aminobiphenyl | |
| CN109320554B (en) | Novel method for synthesizing practical acetaminoacrylate compound | |
| KR100401284B1 (en) | Method for preparing 1-bromoethyl acetate | |
| CN108047157B (en) | Method for synthesizing 2-aminobenzoxazole heterocyclic compound in one step | |
| Wiedemann et al. | Functionalized aminocyclopropanes from functionalized organozinc compounds and N, N-dialkylcarboxamides | |
| BR0100689A (en) | Cyclic acid manufacturing | |
| CN110862311B (en) | Synthesis method of 1-hydroxycyclopropanecarboxylic acid and carboxylate | |
| Fujii et al. | Research on Liebeskind-Srogl coupling/intramolecular Diels-Alder reaction cascade | |
| TW201730173A (en) | Process for the synthesis of intermediates of NEBIVOLOL | |
| CN114213361B (en) | Preparation method of thiamine 1, 4-naphthoquinone compound | |
| CN107602602A (en) | A kind of synthetic method of the pinacol borate of 3 cyanopyridine 5 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |