CN106928171B - Fmoc-Arg(Pbf) the synthetic method of-OH - Google Patents
Fmoc-Arg(Pbf) the synthetic method of-OH Download PDFInfo
- Publication number
- CN106928171B CN106928171B CN201710305099.XA CN201710305099A CN106928171B CN 106928171 B CN106928171 B CN 106928171B CN 201710305099 A CN201710305099 A CN 201710305099A CN 106928171 B CN106928171 B CN 106928171B
- Authority
- CN
- China
- Prior art keywords
- pbf
- arg
- fmoc
- synthetic method
- boc
- 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.)
- Active
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Lubricants (AREA)
Abstract
The present invention relates to the synthetic methods of Fmoc-Arg (Pbf)-OH, belong to arginic protection technique field.The synthetic method of Fmoc-Arg (Pbf)-OH of the invention is first by arginic carboxyl esterification; Boc base is introduced on amino again amido protecting gets up, Pbf group is introduced on guanidine radicals, sloughs Boc group; saponification finally introduces Fmoc group on amino.Fmoc-Arg (Pbf)-OH is synthesized using method of the invention, only needing can be Arg total overall reaction using 1.1 times of Pbf-Cl, still there is arginine unreacted when the dosage of Pbf-Cl is arginic 2 times compared with prior art, Pbf-Cl dosage of the invention substantially reduces, and without Arg remnants, Pbf-Cl is expensive, therefore cost of the invention is greatly reduced, and is conducive to industrial application.
Description
Technical field
The present invention relates to the synthetic methods of Fmoc-Arg (Pbf)-OH, belong to arginic protection technique field.
Background technique
Arginine is that one kind can spontaneous essential amino acid in vivo.In life science, in order to avoid
The generation of by-product, it is necessary to which arginic amino and guanidine radicals are protected.
Fmoc-Arg (Pbf)-OH is exactly that Fmoc (9-fluorenylmethyloxycarbonyl) is utilized to protect amino, with Pbf (2,2,4,6,7-
Pentamethyl benzofuran -5- sulfonyl) protection guanidine radicals.
Synthesis [J] chemical reagent of abundant equal .Fmoc-Arg (the Pbf)-OH of big vast a large bell, 2006,28 (1), 57~58.It discloses
A kind of synthetic method of Fmoc-Arg (Pbf)-OH, this method carries out intermediate protection to amino using Cbz (benzyloxycarbonyl group), in guanidine
Cbz is sloughed after introducing Pbf on base, then introduces Fmoc on amino, is protected using the Cbz of the above method in aqueous phase reactions, Pbf-
Cl consumption is very high, is easy to decompose, and reaction is not thorough, Pbf is expensive thus benefit is unobvious, non-industrial applications.
Application No. is 200810034390.9 Chinese patent applications to disclose a kind of arginine double-protective preparation technique,
After first protecting amino with Boc (tertbutyloxycarbonyl), then Pbf is introduced on guanidine radicals, then slough the Boc on amino, introduce Fmoc pairs
Arginine is protected.The above method avoids hydrogenolysis, product purity >=99.0%, and total recovery can reach 63.51%.But
It is to use the dosage of above method Pbf-Cl big, also has a large amount of arginine remnants, the dosage of Pbf-Cl is arginic 2 times
When, still there is arginine unreacted.
In addition, in the prior art, when introducing Pbf, reaction temperature must be controlled at -15 DEG C~+15 DEG C of lower temperature,
If it is high to increase reaction temperature, reaction effect can be excessively poor, and Pbf consumption will increase, while by-product can be very serious, generates big
The citrulling derivative and ornithine derivative of amount, purifying is difficult, does not have economic benefit.The prior art is preferably at 5-10 DEG C
Pbf is introduced, but Pbf consumption is still very big, ineffective, therefore, since 2006, applicant just stopped using original work
Skill starts to be dedicated to researching and developing profitable new process.
Summary of the invention
The present invention provides the synthetic method of Fmoc-Arg (Pbf)-OH a kind of, the dosage of Pbf-Cl is reduced, at low cost.
In order to solve the above technical problems, the synthetic method of Fmoc-Arg (Pbf)-OH of the invention includes the following steps:
(1) it is esterified
(2) Boc group is introduced
(3) Pbf is introduced
(4) Boc is taken off
(5) it is saponified
(6) Fmoc-Arg (Pbf)-OH is synthesized
Wherein, the R is methyl, ethyl, propyl, isopropyl, normal-butyl, tert-butyl, benzyl, benzhydryl or triphen first
At least one of base.
Preferably, the R is methyl or ethyl.
Preferably, the preferred arginine monohydrochloride of the arginine or arginine alkali.
Preferably, the technique of step (1) esterification includes the following steps:
A1. thionyl chloride, reaction temperature -10~0 DEG C are added dropwise into dehydrated alcohol or anhydrous methanol；
B1. Arg.HCl is added, is warming up to 0 DEG C~50 DEG C and reacts 24~72 hours；
C1. after reaction, it is concentrated under reduced pressure to give Arg.Oet.2HCl the Arg.OMe.2HCl intermediate of grease.
Preferably, the molar ratio of the dehydrated alcohol or anhydrous methanol and thionyl chloride are as follows: 5~30:1.
Preferably, the technique that Pbf is introduced described in step (3) includes the following steps:
A3. molar ratio Boc-ArgOR.HCl:Pbf-Cl: solvent: potassium carbonate is taken: water=1:1~2:15~90:3~8:1
~20 material mixes；
B3. after the reaction was completed, filter, remove solid insoluble, vacuum distillation removes solvent, obtains Boc-Arg (Pbf)
OR；
Wherein, the solvent is tetrahydrofuran, dioxane, at least one of acetone.
Preferably, a3 step temperature maintains 40~45 DEG C.
Preferably, the molar ratio of Boc-ArgOR.HCl:Pbf-Cl described in a3 step is 1:1.1.
Preferably, the technique of step (5) described saponification includes the following steps:
Add ethyl alcohol to dissolve H-Arg (Pbf) OR that step (4) obtains, adjusts pH 10~12 and be saponified, saponification time
It 3~4 hours, purifies up to H-Arg (Pbf) OH.
Preferably, step 5 controls pH 10~12 using sodium hydroxide solution.
The utility model has the advantages that
Fmoc-Arg (Pbf)-OH is synthesized using method of the invention, it is only necessary to use 1.1 times of Pbf-Cl of arg mole
Can still there be arginine not anti-when the dosage of Pbf-Cl is arginic 2 times compared with prior art arg total overall reaction
It answers, Pbf-Cl dosage of the invention substantially reduces, and without arg remnants, Pbf-Cl is expensive, therefore cost of the invention
It substantially reduces, in addition, the introducing temperature of Pbf is high, it is profitable, be conducive to industrial application.
Specific embodiment
The synthetic method of Fmoc-Arg (Pbf)-OH of the invention includes the following steps:
(1) it is esterified
(2) Boc group is introduced
(3) Pbf is introduced
(4) Boc is taken off
(5) it is saponified
(6) Fmoc-Arg (Pbf)-OH is synthesized
Wherein, the R is methyl, ethyl, propyl, isopropyl, normal-butyl, tert-butyl, benzyl, benzhydryl or triphen first
At least one of base.
Preferably, the R is methyl or ethyl
Preferably, the preferred arginine monohydrochloride of the arginine or arginine alkali.
Preferably, the technique of step (1) described esterification includes the following steps:
A1. thionyl chloride, reaction temperature -10~0 DEG C are added dropwise into dehydrated alcohol or anhydrous methanol；
B1. Arg.HCl is added, heats up naturally, 0 DEG C~50 DEG C are reacted 24~72 hours；
C1. after reaction, it is concentrated under reduced pressure to give Arg.Oet.2HCl the Arg.OMe.2HCl intermediate of grease.
Preferably, the molar ratio of the dehydrated alcohol or anhydrous methanol and thionyl chloride are as follows: 5~30:1.
Preferably, the technique that Pbf is introduced described in step (3) includes the following steps:
A3. molar ratio Boc-ArgOR.HCl:Pbf-Cl: solvent: potassium carbonate is taken: water=1:1~2:15~90:3~8:1
~20 material mixes；
B3. after the reaction was completed, filter, remove solid insoluble, vacuum distillation removes solvent, obtains Boc-Arg (Pbf)
OR；
Wherein, the solvent is tetrahydrofuran, dioxane, at least one of acetone.
Preferably, a3 step temperature maintains 40~45 DEG C.
Preferably, the molar ratio of Boc-ArgOR.HCl:Pbf-Cl described in a3 step is 1:1.1.
Preferably, the technique of step (5) described saponification includes the following steps:
Add ethyl alcohol to dissolve H-Arg (Pbf) OR that step (4) obtains, adjusts pH 10~12 and be saponified, saponification time
It 3~4 hours, purifies up to H-Arg (Pbf) OH.
Preferably, step 5 controls pH 10~12 using sodium hydroxide solution.
A specific embodiment of the invention is further described below with reference to embodiment, is not therefore limited the present invention
System is among the embodiment described range.
Embodiment 1
(1) it is esterified
A1. 100L dehydrated alcohol being added in pre-dry 300L reaction kettle, logical brine ice is cooled to -5~-10 DEG C,
Thionyl chloride 13L is added dropwise.
B1. the Arg.HCl 21.5kg of D type is added, closes brine ice, warms naturally to room temperature reaction 24 hours.
C1. 35 DEG C of reactions are warming up to, TLC contact plate tracks response situation, and reaction about 48h terminates.
D1. it is concentrated: after reaction, being concentrated under reduced pressure to give the ArgOet2HCl intermediate of grease.
(2) Boc group is introduced
A2. 150L water is added in 300L reaction kettle, adds sodium bicarbonate 25.2kg, stirs；
It is gradually added into ArgOet2HCl grease；Tetrahydrofuran 30L is added；(Boc) is added portionwise2O, 26.2kg are stirred
It mixes, reacts at room temperature；
TLC method contact plate tracks response situation, starts to process when ArgOet2HCl has reacted.
B2. it is acidified: adjusting pH 3-4 after the reaction was completed, with petrol ether/ethyl acetate (50L:25L), extraction；
C2. plus salt loading, readjustment PH 6-7 mention product with ethyl acetate, with saturated common salt water washing organic phase.
D2. it dries: to the anhydrous sodium sulfate that 60kg is added in organic phase (in the ethyl acetate solution with product), drying 8
Hour.
E2. purification concentration: leaching out solid sodium sulfate, is evaporated under reduced pressure ethyl acetate phase.The Boc- obtained after concentration
ArgOet.HCl grease.
(3) Pbf is introduced
A3. the Boc-ArgOet.HCl that step 2 obtains, Pbf-Cl 31.9kg, acetone are added in 300L reaction kettle
200L, potassium carbonate 41.7kg, stirring add a small amount of water, maintain 40-45 DEG C of temperature, are monitored and are reacted with TLC, to Boc-
ArgOet.HCl reacts completely to be filtered,
B3. it filters, removes solid insoluble, be evaporated under reduced pressure acetone, obtain Boc-Arg (Pbf) Oet grease after concentration
For use.
(4) Boc is taken off
A4. in dry 300L reaction kettle, 3N HCl/ ethyl acetate solution 120L is added, is added with stirring Boc-Arg
(Pbf) Oet grease maintains 10-15 DEG C of temperature, is stirred at room temperature.
B4. after the completion of taking off Boc, add water washing, product is washed till water phase, proper amount of sodium carbonate is added to adjust water phase pH7.
(5) it is saponified
A5. water phase obtained by step (4) is added into 95% ethyl alcohol 100L, stirred, 10N NaOH aqueous solution is added dropwise and adjusts pH 11-
12 are saponified.
B5. after saponification, the pH value for adjusting reaction solution with 6NHCl is cooled to -10-0 DEG C of freezing and crystallizings to 7；From
The heart, solid is stirred with ethyl acetate washes primary, centrifuge dripping collection solid；It is recrystallized to give H-Arg (Pbf) OH solid.
(6) Fmoc-Arg (Pbf)-OH is synthesized
A6. H-Arg (Pbf)-OH, water 120L, THF is added in a kettle and uses Na2CO3Adjust PH=8.5.
B6. it is gradually added into Fmoc-Osu (fluorenes methoxy carbonyl acyl succinimide), controls 15-20 DEG C of temperature, PH=8-9 is with handle
Arg (Pbf) has reacted, and avoids Fmoc-Osu excessive as far as possible.
TLC contact plate tracks response situation, calculates since adding Fmoc-Osu, the reaction time 6 hours.
C6. it purifies: being extracted with petrol ether/ethyl acetate (2:1)；Water phase is acidified to pH=3 with HCl, stirs 2 hours.Acid
Change 0-10 DEG C of temperature；Add ethyl acetate extracted products；PH, which is washed to, with saturated common salt reaches 6；Anhydrous sodium sulfate is dry, and vacuum is taken out
Solid is filtered out, filtrate concentration is concentrated under reduced pressure to give solid, obtains the product in a vacuum and drying environment.
Product purity 99.6%, largest single impurity 0.09%, L-type isomers 0.15%.
Embodiment 2
(1) it is esterified
A1. 100L anhydrous methanol being added in pre-dry 300L reaction kettle, logical brine ice is cooled to -5~-10 DEG C,
Thionyl chloride 13L is added dropwise.
B1. the Arg.HCl 21.5kg of L-type is added, closes brine ice, warms naturally to room temperature reaction 24 hours.
C1. 35 DEG C of reactions are warming up to, TLC contact plate tracks response situation, and reaction terminates for about 48 hours.
D1. it is concentrated: after reaction, being concentrated under reduced pressure to give the ArgOMe2HCl intermediate of grease.
(2) Boc group is introduced
A2. 150L water is added in 300L reaction kettle, adds sodium bicarbonate 25.2kg, stirs；
It is gradually added into ArgOMe2HCl grease；Tetrahydrofuran 30L is added；(Boc) is added portionwise2O, 26.16kg
Stirring, room temperature reaction；
TLC method contact plate tracks response situation, starts to process when ArgOMe2HCl has reacted.
B2. it is acidified: adjusting pH 3-4 after the reaction was completed, extracted with petrol ether/ethyl acetate (50L:25L),
C2. plus salt loading, readjustment pH 6-7 mention product with ethyl acetate, with saturated common salt water washing organic phase.
D2. it dries: to the anhydrous sodium sulfate that 70kg is added in organic phase (in the ethyl acetate solution with product), drying 8
Hour.
E2. purification concentration: leaching out solid sodium sulfate, is evaporated under reduced pressure ethyl acetate phase.The Boc- obtained after concentration
ArgOMe.HCl grease.
(3) Pbf is introduced
A3. the Boc-ArgOMe.HCl that step 2 obtains, Pbf-Cl 31.9kg, acetone are added in 300L reaction kettle
200L, potassium carbonate 41.7kg, stirring, add a small amount of water；40-45 DEG C of temperature is maintained, is monitored and is reacted with TLC, to Boc-
ArgOet.HCl reacts completely to be filtered,
B3. it filters, removes solid insoluble, be evaporated under reduced pressure acetone, obtain Boc-Arg (Pbf) OMe grease after concentration
For use.
(4) Boc is taken off
A4. in dry 300L reaction kettle, 3NHCl/ ethyl acetate solution 120L is added, is added with stirring Boc-Arg
(Pbf) OMe.HCl grease maintains 10-15 DEG C of temperature.It is stirred at room temperature.
B4. after the completion of taking off Boc, add water washing, product is washed till water phase, proper amount of sodium carbonate is added to adjust water phase pH7.
(5) it is saponified
A5. upper gained water phase is added into 95% ethyl alcohol 100L, stirred, 10N NaOH aqueous solution is added dropwise and adjusts pH11-12 progress
Saponification.
B5. after saponification, the pH value for adjusting reaction solution with 6NHCl is cooled to -10-0 DEG C of freezing and crystallizings to 7；From
The heart, solid is stirred with ethyl acetate washes primary, centrifuge dripping collection solid.It is recrystallized to give H-Arg (Pbf) OH solid.
(6) Fmoc-Arg (Pbf)-OH is synthesized
A6. H-Arg (Pbf)-OH, water 120L, THF is added in a kettle, adjusts PH=8.5 with Na2CO3.
B6. it is gradually added into Fmoc-Osu (fluorenes methoxy carbonyl acyl succinimide), controls 15-20 DEG C of temperature, PH=8-9 is with handle
Arg (Pbf) has reacted, and avoids Fmoc-Osu excessive as far as possible.
TLC contact plate tracks response situation, calculates since adding Fmoc-Osu, the reaction time 6 hours.
C6. it purifies: being extracted with petrol ether/ethyl acetate (2:1)；Water phase is acidified to pH=3 with HCl, stirs 2 hours.Acid
Change 0-10 DEG C of temperature；Add ethyl acetate extracted products；PH, which is washed to, with saturated common salt reaches 6；
Add anhydrous sodium sulfate dry, 8 hours；Solid sodium sulfate is removed by suction filtration under vacuum, filtrate concentration is concentrated under reduced pressure to give solid
Body obtains the product in a vacuum and drying environment.
Product purity 99.5%, largest single impurity 0.11%, D type isomers 0.17%
Comparative example
A, B comparative example parallel with tri- groups of C are designed, comparative example A and B are synthesized using preferred method in the prior art
Boc-Arg (Pbf) improves reaction temperature, reaction effect can be excessively poor, and Pbf consumption will increase, while by-product in the prior art
Object can be very serious, and preferred reaction temperature is 5-10 DEG C.Comparative example C synthesizes Boc-Arg (Pbf) using method of the invention.
Comparative example A: Boc-Arg.HCl.H is added in 300ml acetone2O 32.88g (water content 6.1%, 0.1mol),
Stirring maintains 5-10 DEG C of temperature, maintains pH 10-12, is gradually added into Pbf-Cl, and it is small to react 3-4 for 31.77g (0.11mol) sampling
When sample, HPLC measure residue Boc-Arg.HCl.H2O amount M1。
Comparative example B: Boc-Arg.HCl.H is added in 300ml acetone2O 32.88g (water content 6.1%, 0.1mol),
Stirring maintains 5-10 DEG C of temperature, maintains pH 10-12, and Pbf-Cl is added, and 57.76 (0.2mol), which react 3-4 hours, to be sampled, HPLC
Measure residue Boc-Arg.HCl.H2O amount M2。
Comparative example C: being added Boc-Arg-Oet.HCl.33.9g (0.1mol) in 300ml acetone, and stirring maintains pH
10-12 maintains temperature 40-45 DEG C of addition Pbf-Cl, 31.77g (0.11mol), reacts 3-4 hours, TLC detection, and ninhydrin is aobvious
Color, Boc-Arg-Oet.HCl is without residue.
As a result:
Measure the M of A1Boc-Arg.HCl.H2O residue 24.4%, the M of B2Boc-Arg.HCl.H2O residue 4.6%.C's
Boc-Arg-Oet.HCl reacts completely.
It can be seen by comparative example, in the case where being lacked using technical solution of the present invention Pbf-Cl dosage, arginine also can be complete
Full response, Pbf-Cl is expensive, therefore cost of the invention is greatly reduced, and is conducive to industrial application.
Claims (12)
- The synthetic method of 1.Fmoc-Arg (Pbf)-OH, which comprises the steps of:(1) it is esterified(2) Boc group is introduced(3) Pbf is introduced(4) Boc is taken off(5) it is saponified(6) Fmoc-Arg (Pbf)-OH is synthesizedWherein, the R is methyl or ethyl.
- 2. the synthetic method of Fmoc-Arg (Pbf)-OH according to claim 1, which is characterized in that the arginine is essence Propylhomoserin hydrochloride or arginine alkali.
- 3. the synthetic method of Fmoc-Arg (Pbf)-OH according to claim 2, which is characterized in that step (1) esterification Technique includes the following steps:A1. thionyl chloride, reaction temperature -10~0 DEG C are added dropwise into dehydrated alcohol or anhydrous methanol；B1. Arg.HCl is added, is warming up to 0 DEG C~50 DEG C and reacts 24~72 hours；C1. after reaction, it is concentrated under reduced pressure, obtains Arg.Oet.2HCl the Arg.OMe.2HCl intermediate of grease.
- 4. the synthetic method of Fmoc-Arg (Pbf)-OH according to claim 3, which is characterized in that the dehydrated alcohol or The molar ratio of anhydrous methanol and thionyl chloride are as follows: 5~30:1.
- 5. the synthetic method of described in any item Fmoc-Arg (Pbf)-OH according to claim 1-4, which is characterized in that step (3) technique of the introducing Pbf described in includes the following steps:A3. molar ratio Boc-ArgOR.HCl:Pbf-Cl: solvent: potassium carbonate is taken: water=1:1~2:15~90:3~8:1~20 Material, mix；B3. after the reaction was completed, filter, remove solid insoluble, vacuum distillation removes solvent, obtains Boc-Arg (Pbf)-OR；Wherein, the solvent is tetrahydrofuran, dioxane, at least one of acetone.
- 6. the synthetic method of Fmoc-Arg (Pbf)-OH according to claim 5, which is characterized in that a3 step temperature maintains 40~45 DEG C.
- 7. the synthetic method of Fmoc-Arg (Pbf)-OH according to claim 5, which is characterized in that Boc- described in a3 step The molar ratio of ArgOR.HCl:Pbf-Cl is 1:1.1.
- 8. according to claim 1~4, synthetic method of 6,7 described in any item Fmoc-Arg (Pbf)-OH, which is characterized in that The technique of step (5) described saponification includes the following steps:Add ethyl alcohol to dissolve H-Arg (Pbf) OR that step (4) obtains, adjusts pH 10~12 and be saponified, saponification time 3~4 Hour, it purifies up to H-Arg (Pbf) OH.
- 9. the synthetic method of Fmoc-Arg (Pbf)-OH according to claim 5, which is characterized in that step (5) described soap The technique of change includes the following steps:Add ethyl alcohol to dissolve H-Arg (Pbf) OR that step (4) obtains, adjusts pH 10~12 and be saponified, saponification time 3~4 Hour, it purifies up to H-Arg (Pbf) OH.
- 10. according to claim 1~4, the synthetic method of 6,7,9 described in any item Fmoc-Arg (Pbf)-OH, feature exist In step (5) controls pH 10~12 using sodium hydroxide solution.
- 11. the synthetic method of Fmoc-Arg (Pbf)-OH according to claim 5, which is characterized in that step (5) uses hydrogen Sodium hydroxide solution controls pH 10~12.
- 12. the synthetic method of Fmoc-Arg (Pbf)-OH according to claim 8, which is characterized in that step (5) uses hydrogen Sodium hydroxide solution controls pH 10~12.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710305099.XA CN106928171B (en) | 2017-05-03 | 2017-05-03 | Fmoc-Arg(Pbf) the synthetic method of-OH |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710305099.XA CN106928171B (en) | 2017-05-03 | 2017-05-03 | Fmoc-Arg(Pbf) the synthetic method of-OH |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106928171A CN106928171A (en) | 2017-07-07 |
| CN106928171B true CN106928171B (en) | 2019-08-13 |
Family
ID=59429816
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710305099.XA Active CN106928171B (en) | 2017-05-03 | 2017-05-03 | Fmoc-Arg(Pbf) the synthetic method of-OH |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106928171B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109470799B (en) * | 2018-12-29 | 2021-07-27 | 成都市科隆化学品有限公司 | Fmoc-Arg (Pbf) -OH purity and impurity localization detection method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101250172A (en) * | 2008-03-07 | 2008-08-27 | 上海瀚鸿化工科技有限公司 | Arginine double-protective preparation technique |
| WO2015154031A1 (en) * | 2014-04-03 | 2015-10-08 | Amgen Inc. | Method for preparing amg 416 |
-
2017
- 2017-05-03 CN CN201710305099.XA patent/CN106928171B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101250172A (en) * | 2008-03-07 | 2008-08-27 | 上海瀚鸿化工科技有限公司 | Arginine double-protective preparation technique |
| WO2015154031A1 (en) * | 2014-04-03 | 2015-10-08 | Amgen Inc. | Method for preparing amg 416 |
Non-Patent Citations (2)
| Title |
|---|
| Fmoc-Arg(Pbf)-OH 的合成;洪镛裕等;《化学试剂》;20061231;第28卷(第1期);全文 |
| Synthesis of L-octaarginine through microencapsulated palladium-catalyzed allyl ester deprotection;Perez-Lopez, Ana M.等;《Synlett》;20141231;第25卷(第16期);全文 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106928171A (en) | 2017-07-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109678927B (en) | Glutathione total synthesis method based on phosphate carrier | |
| CN101654473A (en) | Synthesis method of amino-protecting glycine dipeptidase derivant | |
| CN107935875B (en) | Method for synthesizing melphalan | |
| CN105541844A (en) | Simple preparation method of high-purity linagliptin | |
| CN106928171B (en) | Fmoc-Arg(Pbf) the synthetic method of-OH | |
| SG183658A1 (en) | Method for preparing combretastatin | |
| CN101863785A (en) | Environmental-protection preparation method of betaine hydrochloride | |
| CN100593536C (en) | Method for synthesizing N-fluorene methoxycarbonyl-N-trityl-D-glutamine | |
| US20110319608A1 (en) | Process for preparing a mixed salt of glucosamine sulfate and an alkali metal chloride | |
| CN104592081B (en) | A kind of synthetic method of aztreonam main ring | |
| CN101200434A (en) | Preparation method for (Z)-7-chloro-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid | |
| CN106565607B (en) | A kind of synthetic method of N-BETA-Alanyl-L-histidine | |
| CN101778824B (en) | Process for producing toluidine compound | |
| CN107814754A (en) | A kind of preparation method of lauroyl arginine ethyl ester hydrochloride | |
| CN104098462B (en) | The method for splitting of the diphenyl-propionic acid racemoid of 2 hydroxyl, 3 methoxyl group 3,3 | |
| CN106905262A (en) | A kind of method for preparing the HEPES of high-purity 4 | |
| CN111205216A (en) | Method for preparing saxagliptin | |
| CN106946724B (en) | The synthetic method of monoamine base inhibitor class intermediate 2- acetylaminohydroxyphenylarsonic acid 2- benzyl malonic acid mono ethyl ester | |
| CN106117204B (en) | The preparation method of the carboxylic acid of Lei Dipawei intermediates (1R, 3S, 4S) 2 Boc 2 azabicyclo [2.2.1] pentane 3 | |
| CN107001250B (en) | A method of Ao Dangka is prepared for intermediate | |
| CN105461606B (en) | The preparation method of high-purity Lei Dipawei intermediates | |
| EP3126324B1 (en) | A process for preparation of levothyroxine and salts thereof | |
| CN103467324B (en) | Preparation method of N, N-dimethylglycine for industrial production | |
| CN106905177A (en) | A kind of preparation method of the biphenyl propionic acid ethyl ester derivative hydrochloride of 2 amino 3 | |
| KR100336139B1 (en) | Novel peptide active materials and methods for their preparation |
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 | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Synthesis of Fmoc Arg (PBF) - oh Effective date of registration: 20211026 Granted publication date: 20190813 Pledgee: Chengdu SME financing Company Limited by Guarantee Pledgor: CHENGDU ZHENGYUAN BIOCHEMICAL TECHNOLOGY CO.,LTD. Registration number: Y2021980011334 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230505 Granted publication date: 20190813 Pledgee: Chengdu SME financing Company Limited by Guarantee Pledgor: CHENGDU ZHENGYUAN BIOCHEMICAL TECHNOLOGY CO.,LTD. Registration number: Y2021980011334 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Synthesis Method of Fmoc Arg (Pbf) - OH Effective date of registration: 20230509 Granted publication date: 20190813 Pledgee: Chengdu SME financing Company Limited by Guarantee Pledgor: CHENGDU ZHENGYUAN BIOCHEMICAL TECHNOLOGY CO.,LTD. Registration number: Y2023980040074 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |