CN113480463A - Synthetic method and preparation device of natural amino acid derivative - Google Patents
Synthetic method and preparation device of natural amino acid derivative Download PDFInfo
- Publication number
- CN113480463A CN113480463A CN202110760379.6A CN202110760379A CN113480463A CN 113480463 A CN113480463 A CN 113480463A CN 202110760379 A CN202110760379 A CN 202110760379A CN 113480463 A CN113480463 A CN 113480463A
- Authority
- CN
- China
- Prior art keywords
- mixture
- stirring
- composition
- reaction
- liquid
- 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.)
- Pending
Links
- 150000003862 amino acid derivatives Chemical class 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 238000010189 synthetic method Methods 0.000 title abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 187
- 238000003756 stirring Methods 0.000 claims abstract description 63
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 31
- 239000007788 liquid Substances 0.000 claims abstract description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 238000001914 filtration Methods 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000000605 extraction Methods 0.000 claims abstract description 11
- 239000000843 powder Substances 0.000 claims abstract description 10
- 239000013078 crystal Substances 0.000 claims abstract description 9
- 238000007865 diluting Methods 0.000 claims abstract description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 6
- 238000005406 washing Methods 0.000 claims abstract description 6
- 238000004108 freeze drying Methods 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 230000002194 synthesizing effect Effects 0.000 claims description 14
- 239000003638 chemical reducing agent Substances 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 239000002994 raw material Substances 0.000 claims description 7
- 238000006073 displacement reaction Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- KPVXTRPRSOUYMZ-YFKPBYRVSA-N (2s)-5-methyl-3,4-dihydro-2h-pyrrole-2-carboxylic acid Chemical compound CC1=N[C@H](C(O)=O)CC1 KPVXTRPRSOUYMZ-YFKPBYRVSA-N 0.000 claims description 5
- YNSYWEFVEIFJPZ-WHFBIAKZSA-N (2s,5s)-5-methylpyrrolidin-1-ium-2-carboxylate Chemical compound C[C@H]1CC[C@@H](C([O-])=O)[NH2+]1 YNSYWEFVEIFJPZ-WHFBIAKZSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- WMSUFWLPZLCIHP-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 9h-fluoren-9-ylmethyl carbonate Chemical group C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)ON1C(=O)CCC1=O WMSUFWLPZLCIHP-UHFFFAOYSA-N 0.000 claims description 4
- TZNBTMCEMLXYEM-ZDUSSCGKSA-N 2-o-benzyl 1-o-tert-butyl (2s)-5-oxopyrrolidine-1,2-dicarboxylate Chemical compound C1CC(=O)N(C(=O)OC(C)(C)C)[C@@H]1C(=O)OCC1=CC=CC=C1 TZNBTMCEMLXYEM-ZDUSSCGKSA-N 0.000 claims description 4
- 241000349731 Afzelia bipindensis Species 0.000 claims description 4
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical group [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 238000002156 mixing Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Abstract
The invention relates to the technical field of chemical synthesis, in particular to a synthetic method and a preparation device of natural amino acid derivatives; dissolving the second composition by using a second reagent to obtain a fifth mixture, carrying out nitrogen replacement reaction, stirring the fifth mixture, waiting for reaction to obtain a sixth mixture, filtering the sixth mixture to obtain a third composition, adding the first liquid and water into the third composition, stirring, sequentially adding the first crystal and the first powder, waiting for reaction to obtain a seventh mixture, diluting the seventh mixture, carrying out extraction reaction on the diluted seventh mixture, washing with saturated common salt water, filtering the seventh mixture, and freeze-drying to obtain a fourth composition, thereby realizing improvement of the yield of Fmoc-S-5-methylproline.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a synthetic method and a preparation device of a natural amino acid derivative.
Background
The relatively rare synthesis of Fmoc-S-5-methylproline compounds, which are mainly useful as intermediates or as catalysts, wherein changes in their configuration can be used as intermediates for the synthesis of Destrixin B (DB), also known as cyclodipeptide, which inhibits the activity of colorectal cancer cells (CRC) HT-29, inhibits the proliferation of SW48o, H1229 and HCT116 cells and induces cell cycle arrest. Activation of the mitochondria-dependent caspase cascade plays an important role in DB induction of apoptotic cell death in S549 cells.
The yield of Fmoc-S-5-methylproline currently produced is not high.
Disclosure of Invention
The invention aims to provide a synthetic method and a preparation device of a natural amino acid derivative, and aims to solve the technical problem of poor yield of Fmoc-S-5-methylproline in the prior art.
In order to achieve the above object, the present invention provides a method for synthesizing a natural amino acid derivative, comprising the steps of:
dissolving the first composition with a first reagent, stirring and adding a third liquid to obtain a fourth mixture;
after stirring the fourth mixture, concentrating the fourth mixture to obtain a second composition;
dissolving the second composition by using a second reagent to obtain a fifth mixture, and performing nitrogen displacement reaction;
stirring the fifth mixture, and waiting for reaction to obtain a sixth mixture;
filtering the sixth mixture to obtain a third synthetic product;
adding a first liquid and water into the third composition, stirring, sequentially adding a first crystal and a first powder, waiting for reaction to obtain a seventh mixture, and diluting the seventh mixture;
carrying out extraction reaction on the diluted seventh mixture, and washing with saturated saline water;
filtering the seventh mixture and lyophilizing to obtain a fourth composition.
In the step of dissolving the first composition using the first reagent, stirring and adding the third liquid to obtain a fourth mixture, obtaining the first composition by:
adding the first liquid into the raw materials to obtain a first mixture, and carrying out nitrogen replacement reaction on the first mixture;
slowly dripping a metal reagent into the first mixture, stirring, and waiting for reaction to obtain a second mixture;
pouring the second mixture into the first aqueous solution, and extracting by using a second liquid to obtain a third mixture;
and drying the third mixture to obtain the first composition.
In the steps of dissolving the first composition using the first reagent, stirring and adding the third liquid to obtain a fourth mixture and dissolving the second composition using the second reagent to obtain a fifth mixture, and performing a nitrogen substitution reaction:
the first composition is benzyl (S) -2- (tert-butoxycarbonyl) amino-5-oxoacetic acid, the first reagent is DCM, the third liquid is TFA, and the second reagent is MeOH.
Wherein, after stirring the fourth mixture, the step of concentrating the fourth mixture to obtain the second composition comprises:
the stirring temperature is 20 ℃, the stirring time is 16 hours, and the second composition is (S) -5-methyl-3, 4-dihydro-2H-pyrrole-2-carboxylate.
In the steps of stirring said fifth mixture, waiting for the reaction to obtain a sixth mixture and freeze-drying said seventh mixture after filtration to obtain a fourth composition:
stirring temperature is 20 ℃, stirring time is 16 hours, and the fourth composition is Fmoc-S-5-methylproline.
In the step of adding the first liquid and water to the third composition, stirring and adding the first crystal and the first powder in order, waiting for a reaction to obtain a seventh mixture, and diluting the seventh mixture:
the third compound is (2S,5S) -5-methylpyrrolidine-2-carboxylic acid, the first liquid is THF, and the first crystalThe body is NaHCO3The first powder is Fmoc-OSu, the reaction temperature is 20 ℃, and the reaction time is 15 hours.
In the step of adding a first liquid to the raw materials to obtain a first mixture, and subjecting the first mixture to a nitrogen substitution reaction:
the raw material is Boc-L-pyroglutamic acid benzyl ester, and the nitrogen replacement reaction temperature is normal temperature.
In the step of slowly dropping a metal reagent into the first mixture, stirring, and waiting for a reaction to obtain a second mixture:
the metal reagent is MeLi, and the temperature when the metal reagent is dripped is-78 ℃.
In the step of pouring the second mixture into the first aqueous solution, performing extraction using the second liquid to obtain a third mixture:
the first aqueous solution is saturated NH4Cl, twice times of extraction.
The invention also provides a preparation device adopting the synthesis method of the natural amino acid derivative, which comprises the following steps:
including the churn, place board, handle, rotation motor, speed reducer, rotation post, connecting rod and stirring axle, the opening has on the churn, place the board with the churn is dismantled to be connected, and is located in the opening, the handle with place board fixed connection, and be located place the lateral wall of board, rotate the motor with place board fixed connection, and be located in the churn, the speed reducer with the output fixed connection who rotates the motor, the one end that rotates the post with speed reducer fixed connection, the other end that rotates the post with connecting rod fixed connection, the quantity of stirring axle is many, every the stirring axle respectively with connecting rod fixed connection, and all be located the lateral wall of connecting rod.
The rotating motor is matched with the speed reducer to drive the rotating columns to rotate, so that the rotating columns stir the mixture in the stirring cylinder, and the mixture is more uniformly mixed.
The invention relates to a method for synthesizing natural amino acid derivatives and a device for preparing the same, which are characterized in that a first compound is dissolved by using a first reagent, a fourth mixture is obtained by stirring and adding a third liquid, the fourth mixture is concentrated by stirring to obtain a second compound, the second compound is dissolved by using a second reagent to obtain a fifth mixture and is subjected to nitrogen displacement reaction, the fifth mixture is stirred and is subjected to reaction to obtain a sixth mixture, the sixth mixture is filtered to obtain a third compound, the first liquid and water are added into the third compound, the first crystal and the first powder are stirred and sequentially added to the third compound, the reaction is waited to obtain a seventh mixture, the seventh mixture is diluted, and the diluted seventh mixture is subjected to extraction reaction, and washing with saturated saline solution, and finally filtering and freeze-drying the seventh mixture to obtain a fourth compound, thereby realizing the improvement of the yield of Fmoc-S-5-methylproline.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.
FIG. 1 is a flow chart of the steps of the method of synthesizing a natural amino acid derivative of the present invention.
FIG. 2 is a flow chart of the steps of the process of the present invention to obtain a first composition.
FIG. 3 is a purified HPLC purity profile of a fourth composition of the invention.
FIG. 4 is an SFC chiral spectrum of a fourth composition of the invention.
FIG. 5 is a schematic structural view of an apparatus for synthesizing a natural amino acid derivative according to the present invention.
1-stirring cylinder, 2-placing plate, 3-handle, 4-rotating motor, 5-speed reducer, 6-rotating column, 7-connecting rod, 8-stirring shaft and 11-opening.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout.
Referring to fig. 1 to 4, the present invention provides a method for synthesizing a natural amino acid derivative, comprising the following steps:
s1: dissolving the first composition with a first reagent, stirring and adding a third liquid to obtain a fourth mixture;
s2: stirring the fourth mixture at the temperature of 20 ℃ for 16 hours, and then concentrating the fourth mixture to obtain a second composition;
s3: dissolving the second composition by using a second reagent to obtain a fifth mixture, and performing nitrogen displacement reaction;
s4: stirring the fifth mixture at the stirring temperature of 20 ℃ for 16 hours, and waiting for reaction to obtain a sixth mixture;
s5: filtering the sixth mixture to obtain a third synthetic product;
s6: adding a first liquid and water into the third composition, stirring, sequentially adding a first crystal and a first powder, waiting for reaction at the reaction temperature of 20 ℃ for 15 hours to obtain a seventh mixture, and diluting the seventh mixture;
s7: carrying out extraction reaction on the diluted seventh mixture, and washing with saturated saline water;
s8: drying the washed seventh mixture;
s9: filtering the seventh mixture and lyophilizing to obtain a fourth composition.
In this embodiment, the first composition is benzyl (S) -2- (tert-butoxycarbonyl) amino-5-oxoacetic acid, the first reagent is DCM, the third liquid is TFA, the second composition is (S) -5-methyl-3.4-dihydro-2H-pyrrole-2-carboxylate, the second reagent is MeOH, the third composition is (2S,5S) -5-methylpyrrolidine-2-carboxylic acid, the first liquid is THF, the second composition is THF, the third composition is TFA, the third composition is a mixture of compounds, and the third composition is a mixture of compoundsOne crystal is NaHCO3Wherein the first powder is Fmoc-OSu and the fourth composition is Fmoc-S-5-methylproline, first dissolving benzyl (S) -2- (tert-butoxycarbonyl) amino-5-oxoacetic acid using THF, stirring and adding TFA to obtain a fourth mixture, further stirring the fourth mixture at 20 ℃ for 16 hours, concentrating the fourth mixture to obtain (S) -5-methyl-3.4-dihydro-2H-pyrrole-2-carboxylate, dissolving (S) -5-methyl-3.4-dihydro-2H-pyrrole-2-carboxylate using MeOH to obtain a fifth mixture, performing a nitrogen substitution reaction, and stirring the fifth mixture, stirring at 20 ℃ for 16 hours to obtain a sixth mixture, filtering the sixth mixture to obtain (2S,5S) -5-methylpyrrolidine-2-carboxylic acid, adding THF and water into the (2S,5S) -5-methylpyrrolidine-2-carboxylic acid, stirring and sequentially adding NaHCO3And Fmoc-OSu, waiting for reaction, wherein the reaction temperature is 20 ℃, the reaction time is 15 hours, obtaining a seventh mixture, diluting the seventh mixture, performing extraction reaction on the diluted seventh mixture, washing the seventh mixture with saturated saline solution, drying the washed seventh mixture, filtering the seventh mixture, and freeze-drying the seventh mixture to obtain Fmoc-S-5-methylproline, wherein the purity of the obtained Fmoc-S-5-methylproline reaches 99.035%, the purity of the SFC reaches 100%, and the yield of the Fmoc-S-5-methylproline is improved.
The invention also provides a process for obtaining said first composition, comprising the steps of:
s11: adding the first liquid into the raw materials to obtain a first mixture, and performing nitrogen displacement reaction on the first mixture at normal temperature;
s12: slowly dripping a metal reagent into the first mixture at the temperature of minus 78 ℃, stirring, and waiting for reaction to obtain a second mixture;
s13: pouring the second mixture into the first aqueous solution, carrying out quenching reaction, and extracting twice by using a second liquid to obtain a third mixture;
s14: and drying the third mixture to obtain the first composition.
In this embodiment, the starting material is Boc-L-pyroglutamic acid benzyl ester, the metal reagent is MeLi, and the first aqueous solution is saturated NH4Adding THF into Boc-L-pyroglutamic acid benzyl ester to obtain a first mixture, performing nitrogen displacement reaction on the first mixture at normal temperature, slowly dripping MeLi into the first mixture at-78 ℃, stirring, waiting for reaction to obtain a second mixture, and then pouring the second mixture into saturated NH4Quenching reaction in Cl, extraction with MeOH twice to obtain a third mixture, and drying the third mixture to obtain benzyl (S) -2- (tert-butoxycarbonyl) amino-5-oxoacetic acid.
Referring to FIG. 5, the present invention also provides a synthesis preparation apparatus using the above-mentioned natural amino acid derivatives,
comprises a mixing drum 1, a placing plate 2, a handle 3, a rotating motor 4, a speed reducer 5, a rotating column 6, a connecting rod 7 and a stirring shaft 8, the mixing drum 1 is provided with an opening 11, the placing plate 2 is detachably connected with the mixing drum 1, and is positioned in the opening 11, the handle 3 is fixedly connected with the placing plate 2 and is positioned on the outer side wall of the placing plate 2, the rotating motor 4 is fixedly connected with the placing plate 2, and is positioned in the mixing drum 1, the speed reducer 5 is fixedly connected with the output end of the rotating motor 4, one end of the rotating column 6 is fixedly connected with the speed reducer 5, the other end of the rotating column 6 is fixedly connected with the connecting rod 7, the number of the stirring shafts 8 is multiple, and each stirring shaft 8 is fixedly connected with the connecting rod 7 and is positioned on the outer side wall of the connecting rod 7.
In this embodiment, an experimenter places a mixture to be stirred into the stirring cylinder 1 through the opening 11, holds the handle 3, places the placing plate 2 into the opening 11, controls the rotation motor 4 to operate, and the rotation motor 4 is matched with the speed reducer 5 to drive the rotation column 6 to rotate, so that the stirring shaft 8 stirs the mixture in the stirring cylinder 1, and the mixture is mixed more uniformly.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. A method for synthesizing natural amino acid derivatives is characterized by comprising the following steps:
dissolving the first composition with a first reagent, stirring and adding a third liquid to obtain a fourth mixture;
after stirring the fourth mixture, concentrating the fourth mixture to obtain a second composition;
dissolving the second composition by using a second reagent to obtain a fifth mixture, and performing nitrogen displacement reaction;
stirring the fifth mixture, and waiting for reaction to obtain a sixth mixture;
filtering the sixth mixture to obtain a third synthetic product;
adding a first liquid and water into the third composition, stirring, sequentially adding a first crystal and a first powder, waiting for reaction to obtain a seventh mixture, and diluting the seventh mixture;
carrying out extraction reaction on the diluted seventh mixture, and washing with saturated saline water;
filtering the seventh mixture and lyophilizing to obtain a fourth composition.
2. The method for synthesizing a natural amino acid derivative according to claim 1,
in the step of dissolving the first composition using the first reagent, stirring and adding the third liquid to obtain a fourth mixture, obtaining the first composition by:
adding the first liquid into the raw materials to obtain a first mixture, and carrying out nitrogen replacement reaction on the first mixture;
slowly dripping a metal reagent into the first mixture, stirring, and waiting for reaction to obtain a second mixture;
pouring the second mixture into the first aqueous solution, and extracting by using a second liquid to obtain a third mixture;
and drying the third mixture to obtain the first composition.
3. The method for synthesizing a natural amino acid derivative according to claim 1,
in the steps of dissolving the first composition using the first reagent, stirring and adding the third liquid to obtain a fourth mixture and dissolving the second composition using the second reagent to obtain a fifth mixture, and performing a nitrogen substitution reaction:
the first composition is benzyl (S) -2- (tert-butoxycarbonyl) amino-5-oxoacetic acid, the first reagent is DCM, the third liquid is TFA, and the second reagent is MeOH.
4. The method for synthesizing a natural amino acid derivative according to claim 1,
after stirring the fourth mixture, the step of concentrating the fourth mixture to obtain a second composition comprises:
the stirring temperature is 20 ℃, the stirring time is 16 hours, and the second composition is (S) -5-methyl-3, 4-dihydro-2H-pyrrole-2-carboxylate.
5. The method for synthesizing a natural amino acid derivative according to claim 1,
in the steps of stirring said fifth mixture, waiting for the reaction to obtain a sixth mixture and freeze-drying said seventh mixture after filtration to obtain a fourth composition:
stirring temperature is 20 ℃, stirring time is 16 hours, and the fourth composition is Fmoc-S-5-methylproline.
6. The method for synthesizing a natural amino acid derivative according to claim 1,
in the step of adding the first liquid and water to the third composition, stirring and adding the first crystal and the first powder in order, waiting for a reaction to obtain a seventh mixture, and diluting the seventh mixture:
the third compound is (2S,5S) -5-methylpyrrolidine-2-carboxylic acid, the first liquid is THF, and the first crystal is NaHCO3The first powder is Fmoc-OSu, the reaction temperature is 20 ℃, and the reaction time is 15 hours.
7. The method for synthesizing a natural amino acid derivative according to claim 2,
in the step of adding a first liquid to the raw materials to obtain a first mixture, and subjecting the first mixture to a nitrogen substitution reaction:
the raw material is Boc-L-pyroglutamic acid benzyl ester, and the nitrogen replacement reaction temperature is normal temperature.
8. The method for synthesizing a natural amino acid derivative according to claim 2,
in the step of slowly dropping a metal reagent into the first mixture, stirring, and waiting for a reaction to obtain a second mixture:
the metal reagent is MeLi, and the temperature when the metal reagent is dripped is-78 ℃.
9. The method for synthesizing a natural amino acid derivative according to claim 2,
in the step of pouring the second mixture into the first aqueous solution, performing extraction using the second liquid to obtain a third mixture:
the first aqueous solution is saturated NH4Cl, extraction times of twoNext, the process is carried out.
10. The apparatus for producing a natural amino acid derivative according to claim 1,
including the churn, place board, handle, rotation motor, speed reducer, rotation post, connecting rod and stirring axle, the opening has on the churn, place the board with the churn is dismantled to be connected, and is located in the opening, the handle with place board fixed connection, and be located place the lateral wall of board, rotate the motor with place board fixed connection, and be located in the churn, the speed reducer with the output fixed connection who rotates the motor, the one end that rotates the post with speed reducer fixed connection, the other end that rotates the post with connecting rod fixed connection, the quantity of stirring axle is many, every the stirring axle respectively with connecting rod fixed connection, and all be located the lateral wall of connecting rod.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110760379.6A CN113480463A (en) | 2021-07-06 | 2021-07-06 | Synthetic method and preparation device of natural amino acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110760379.6A CN113480463A (en) | 2021-07-06 | 2021-07-06 | Synthetic method and preparation device of natural amino acid derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113480463A true CN113480463A (en) | 2021-10-08 |
Family
ID=77941052
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110760379.6A Pending CN113480463A (en) | 2021-07-06 | 2021-07-06 | Synthetic method and preparation device of natural amino acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113480463A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040229858A1 (en) * | 1999-06-30 | 2004-11-18 | Daiichi Pharmaceutical Co., Ltd. | VLA-4 inhibitor compounds |
| CN109954471A (en) * | 2017-12-26 | 2019-07-02 | 沈阳东瑞精细化工有限公司 | Self-priming sulbactam hydrogenation equipment |
| CN112679407A (en) * | 2021-03-17 | 2021-04-20 | 南京桦冠生物技术有限公司 | Preparation method of chiral 5-substituted proline compound |
-
2021
- 2021-07-06 CN CN202110760379.6A patent/CN113480463A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040229858A1 (en) * | 1999-06-30 | 2004-11-18 | Daiichi Pharmaceutical Co., Ltd. | VLA-4 inhibitor compounds |
| CN109954471A (en) * | 2017-12-26 | 2019-07-02 | 沈阳东瑞精细化工有限公司 | Self-priming sulbactam hydrogenation equipment |
| CN112679407A (en) * | 2021-03-17 | 2021-04-20 | 南京桦冠生物技术有限公司 | Preparation method of chiral 5-substituted proline compound |
Non-Patent Citations (2)
| Title |
|---|
| 来源：FCH公司: "提供的化学品目录", 《数据库REGISTRY(在线)》 * |
| 祝婷婷 等: "Fmoc 保护L-脯氨酸的合成工艺研究", 《化学工程与装备》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101962193B (en) | Method for preparing ZSM-34 and heteroatom substituted molecular sieve thereof by using crystal seed synthesis method | |
| CN107961723A (en) | A kind of novel rotating wheel formula is easy to the pony mixer of discharging | |
| CN1724511A (en) | Method of extracting capsaicin and capsaithin from red pepper | |
| CN116023610B (en) | Covalent organic framework material, ligand structure thereof and application of covalent organic framework material in separation membrane | |
| CN113480463A (en) | Synthetic method and preparation device of natural amino acid derivative | |
| CN106565583A (en) | Preparation method of polysubstitued pyrrole derivative | |
| CN101307040A (en) | Method for separating and preparing paclitaxel | |
| CN102485730A (en) | Synthetic method of DL-fosfomycin calcium | |
| CN112209889A (en) | Method for preparing sulfaquinoxaline without solvent | |
| CN113731011B (en) | Dewatering equipment is used in dihydroxydicyclohexyl propane production and processing | |
| CN108689859B (en) | Production process of p-nitroaniline | |
| CN109012747B (en) | Application of copper (I) coordination polymer | |
| CN1834093A (en) | Synthetic process of chiral 2-amido-1-(6-fluorine-3,4-dihydrobenzopyranyl) alCohol | |
| CN212915432U (en) | Mixing arrangement is used in filter material production | |
| DE2029118A1 (en) | ||
| CN108586257B (en) | Preparation method of parafluoronitrobenzene | |
| CN108328638B (en) | method for preparing ammonium aluminum sulfate from FCC spent catalyst | |
| CN216538484U (en) | Synthetic cauldron of preparation of methoxylamine hydrochloride | |
| CN104725402A (en) | Method for continuously crystallizing 6-amino-penicillanic acid | |
| CN114751883B (en) | Preparation method of benzofuran-3-carboxamide compound | |
| CN117820142A (en) | Preparation method of chiral 4-bromophenylalanine | |
| CN220758953U (en) | Stirring mechanism and stirring device | |
| CN215277290U (en) | High mass transfer efficiency's reation kettle for dyestuff preparation | |
| CN215139812U (en) | Five dimethylamino tantalum preparation facilities | |
| CN220780362U (en) | Glufosinate-ammonium powder reation kettle |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211008 |
|
| RJ01 | Rejection of invention patent application after publication |