CN109160891A - A kind of Fmoc-Cys(Acm)-OH preparation method - Google Patents
A kind of Fmoc-Cys(Acm)-OH preparation method Download PDFInfo
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- CN109160891A CN109160891A CN201811071173.7A CN201811071173A CN109160891A CN 109160891 A CN109160891 A CN 109160891A CN 201811071173 A CN201811071173 A CN 201811071173A CN 109160891 A CN109160891 A CN 109160891A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of Fmoc-Cys(Acm) preparation method of-OH, it is related to chemical technology field.This method comprises the following steps: hydrochloric acid, Cys HCl, Acm and water hybrid reaction are obtained Cys (Acm) solution；Fmoc-OSU is added to Cys (Acm) solution, adjusts pH value of solution to neutral or alkalescent, reaction completely obtains Fmoc-Cys(Acm)-OH crude product；Fmoc-Cys(Acm)-OH crude product successively obtains Fmoc-Cys(Acm through extraction, acidification, washing)-OH product.Cys (Acm) is made in a step of the invention, and Cys (Acm) obtained is directly with Fmoc-OSU up to Fmoc-Cys(Acm)-OH, it is compared with the traditional method, reduce operating process, production efficiency is improved, while reducing organic solvent usage amount, reduces environmental pollution.
Description
Technical field
The present invention relates to chemical technology field, especially a kind of Fmoc-Cys(Acm)-OH preparation method.
Background technique
Fmoc-Cys(Acm)-OH i.e. fluorenylmethyloxycarbonyl-S- acetyl aminomethyl-L-cysteine is among a kind of chemical industry
Body, specifically a kind of amino acid derivativges, are usually used in Peptide systhesis.In the prior art, the Fmoc-Cys(Acm of preparation)-
The method of OH are as follows: in acetum, CysHCl is added, Acm is reacted.After fully reacting, increasing amount acetone is precipitated solid
Body, solid is reacted with Fmoc-OSU again is made Fmoc-Cys(Acm)-OH, qualified products are made in repurity.This method organic solvent
Usage amount is big, and production efficiency bottom is not suitable for present demand of industrial production.
Summary of the invention
Goal of the invention of the invention is: in view of the above problems, providing a kind of Fmoc-Cys(Acm) system of-OH
Cys (Acm) is made one step ahead in Preparation Method, this method head, and Cys (Acm) obtained is directly with Fmoc-OSU up to Fmoc-Cys
(Acm)-OH is compared with the traditional method, and reduces operating process, improves production efficiency, while reducing organic solvent usage amount, is reduced
Environmental pollution.
The technical solution adopted by the invention is as follows:
A kind of Fmoc-Cys(Acm)-OH preparation method comprising following steps:
(1) hydrochloric acid, Cys HCl, Acm and water hybrid reaction are obtained into Cys (Acm) solution；
(2) Fmoc-OSU is added to Cys (Acm) solution, adjusts pH value of solution to neutral or alkalescent, reaction completely obtains
Fmoc-Cys(Acm)-OH crude product；
(3) Fmoc-Cys(Acm)-OH crude product successively obtains Fmoc-Cys(Acm through extraction, acidification, washing)-OH product.
By adopting the above-described technical solution, Cys (Acm) is made in a step, Cys (Acm) obtained is directly and Fmoc-OSU
Up to Fmoc-Cys(Acm)-OH, it is compared with the traditional method, reduces operating process, improve production efficiency, while reducing organic molten
Agent usage amount reduces environmental pollution.
A kind of Fmoc-Cys(Acm of the invention)-OH preparation method, the concentration of hydrochloric acid is 30-37wt% in step (1),
Mass ratio between hydrochloric acid, Cys HCl, Acm and water is 4:(0.8-1.5): (1.6-2.4): (3-5).
A kind of Fmoc-Cys(Acm of the invention)-OH preparation method, reaction temperature be 0-10 DEG C, reaction time 18-
30h。
A kind of Fmoc-Cys(Acm of the invention)-OH preparation method, in step (2), be added into Cys (Acm) solution
Acetone is added while Fmoc-OSU；The mass ratio of acetone, Fmoc-OSU and Acm is (1.8-2.5): (0.8-1.2): 1.
By adopting the above-described technical solution, acetone, which is added, can be improved the rate of dissolution and solubility of Fmoc-OSU, have
Effect promotes the extent of reaction and reaction efficiency.
A kind of Fmoc-Cys(Acm of the invention)-OH preparation method, adjust pH value of solution to 7-8.
A kind of Fmoc-Cys(Acm of the invention)-OH preparation method, in step (3), Fmoc-Cys(Acm)-OH crude product
Extraction select ethyl acetate, ethyl acetate in Acm mass ratio be 2-4:1.
A kind of Fmoc-Cys(Acm of the invention)-OH preparation method, after extraction, the sodium chloride for being 8-15wt% with concentration
Solution washs ethyl acetate layer, is then acidified.
A kind of Fmoc-Cys(Acm of the invention)-OH preparation method, acidification use concentration for the hydrochloric acid of 35-37wt% into
Row, is acidified to that there is no crystal precipitations；Then take crystal, it is obtained by drying after crystal pure water.
In conclusion by adopting the above-described technical solution, the beneficial effects of the present invention are:
The present invention provides a kind of Fmoc-Cys(Acm) preparation method of-OH, Cys (Acm) is made one step ahead in this method head, system
The Cys (Acm) obtained is directly with Fmoc-OSU up to Fmoc-Cys(Acm)-OH, it is compared with the traditional method, reduces operating process, mention
High efficiency, while organic solvent usage amount is reduced, reduce environmental pollution.
Specific embodiment
All features disclosed in this specification or disclosed all methods or in the process the step of, in addition to mutually exclusive
Feature and/or step other than, can combine in any way.
Any feature disclosed in this specification (including any accessory claim, abstract), unless specifically stated,
It is replaced by other equivalent or with similar purpose alternative features.That is, unless specifically stated, each feature is a series of
An example in equivalent or similar characteristics.
Embodiment 1
The present embodiment provides a kind of Fmoc-Cys(Acm) preparation method of-OH, Cys (Acm) is made one step ahead in this method head, system
The Cys (Acm) obtained is directly with Fmoc-OSU up to Fmoc-Cys(Acm)-OH, reduces operating process, improves production efficiency, simultaneously
Reduce organic solvent usage amount.It includes the following steps:
Step 1: taking hydrochloric acid, Cys HCl, Acm and water respectively, and by four mixing, reaction obtains Cys (Acm) solution.
Step 2: Fmoc-OSU, adjusting pH value of solution to neutral or alkalescent, completely after reaction is added to Cys (Acm) solution
Obtain Fmoc-Cys(Acm)-OH crude product.
Step 3: Fmoc-Cys(Acm)-OH crude product successively obtains Fmoc-Cys(Acm through extraction, acidification, washing)-OH product.
Embodiment 2
The present embodiment provides a kind of Fmoc-Cys(Acm) preparation method of-OH, Cys (Acm) is made one step ahead in this method head, system
The Cys (Acm) obtained is directly with Fmoc-OSU up to Fmoc-Cys(Acm)-OH, reduces operating process, improves production efficiency, simultaneously
Reduce organic solvent usage amount.It includes the following steps:
Step 1: taking hydrochloric acid, Cys HCl, Acm and water respectively, is 4:(0.8-1.5 according to mass ratio): (1.6-2.4): (3-
5) four mixing are reacted 18-30h, obtains Cys (Acm) solution under the conditions of reaction temperature is 0-10 DEG C.
Step 2: Fmoc-OSU, adjusting pH value of solution to neutral or alkalescent, completely after reaction is added to Cys (Acm) solution
Obtain Fmoc-Cys(Acm)-OH crude product.
Step 3: Fmoc-Cys(Acm)-OH crude product successively obtains Fmoc-Cys(Acm through extraction, acidification, washing)-OH product.
Embodiment 3
The present embodiment provides a kind of Fmoc-Cys(Acm) preparation method of-OH, Cys (Acm) is made one step ahead in this method head, system
The Cys (Acm) obtained is directly with Fmoc-OSU up to Fmoc-Cys(Acm)-OH, reduces operating process, improves production efficiency, simultaneously
Reduce organic solvent usage amount.It includes the following steps:
Step 1: taking hydrochloric acid, Cys HCl, Acm and water respectively, is 4:(0.8-1.5 according to mass ratio): (1.6-2.4): (3-
5) four mixing are reacted 18-30h, obtains Cys (Acm) solution under the conditions of reaction temperature is 0-10 DEG C.
Step 2: being added Fmoc-OSU to Cys (Acm) solution, while acetone be added, the matter of acetone, Fmoc-OSU and Acm
Amount is than being (1.8-2.5): (0.8-1.2): 1, after mixing, pH value of solution is adjusted to 7-8, obtains Fmoc- after reaction completely
Cys(Acm)-OH crude product.
Step 3: Fmoc-Cys(Acm)-OH crude product successively obtains Fmoc-Cys(Acm through extraction, acidification, washing)-OH product.
Embodiment 4
The present embodiment provides a kind of Fmoc-Cys(Acm) preparation method of-OH, Cys (Acm) is made one step ahead in this method head, system
The Cys (Acm) obtained is directly with Fmoc-OSU up to Fmoc-Cys(Acm)-OH, reduces operating process, improves production efficiency, simultaneously
Reduce organic solvent usage amount.It includes the following steps:
Step 1: taking hydrochloric acid, Cys HCl, Acm and water respectively, is 4:(0.8-1.5 according to mass ratio): (1.6-2.4): (3-
5) four mixing are reacted 18-30h, obtains Cys (Acm) solution under the conditions of reaction temperature is 0-10 DEG C.
Step 2: being added Fmoc-OSU to Cys (Acm) solution, while acetone be added, the matter of acetone, Fmoc-OSU and Acm
Amount is than being (1.8-2.5): (0.8-1.2): 1, after mixing, pH value of solution is adjusted to 7-8, obtains Fmoc- after reaction completely
Cys(Acm)-OH crude product.
Step 3: Fmoc-Cys(Acm)-OH crude product extracted with ethyl acetate, and the mass ratio of ethyl acetate and Acm are 2-
4:1 after extraction, washs ethyl acetate layer with the sodium chloride solution that concentration is 8-15wt%, is then acidified, after precipitating crystal
Take crystal, it is obtained by drying after crystal pure water.
Embodiment 5
The present embodiment provides a kind of Fmoc-Cys(Acm) preparation method of-OH, Cys (Acm) is made one step ahead in this method head, system
The Cys (Acm) obtained is directly with Fmoc-OSU up to Fmoc-Cys(Acm)-OH, reduces operating process, improves production efficiency, simultaneously
Reduce organic solvent usage amount.It includes the following steps:
Step 1: taking hydrochloric acid, Cys HCl, Acm and water respectively, is 4:(0.8-1.5 according to mass ratio): (1.6-2.4): (3-
5) four mixing are reacted 18-30h, obtains Cys (Acm) solution under the conditions of reaction temperature is 0-10 DEG C.
Step 2: being added Fmoc-OSU to Cys (Acm) solution, while acetone be added, the matter of acetone, Fmoc-OSU and Acm
Amount is than being (1.8-2.5): (0.8-1.2): 1, after mixing, pH value of solution is adjusted to 7-8, obtains Fmoc- after reaction completely
Cys(Acm)-OH crude product.
Step 3: Fmoc-Cys(Acm)-OH crude product extracted with ethyl acetate, and the mass ratio of ethyl acetate and Acm are 2-
4:1 after extraction, washs ethyl acetate layer with the sodium chloride solution that concentration is 8-15wt%, is then acidified, and acidification is using dense
The hydrochloric acid that degree is 35-37wt% carries out, and is acidified to that there is no crystal precipitations；Then take crystal, after crystal pure water drying be
?.
The invention is not limited to specific embodiments above-mentioned.The present invention, which expands to, any in the present specification to be disclosed
New feature or any new combination, and disclose any new method or process the step of or any new combination.
Claims (8)
1. a kind of Fmoc-Cys(Acm) preparation method of-OH, which is characterized in that it includes the following steps:
(1) hydrochloric acid, CysHCl, Acm and water hybrid reaction are obtained into Cys (Acm) solution；
(2) Fmoc-OSU is added to Cys (Acm) solution, adjusts pH value of solution to neutral or alkalescent, reaction completely obtains
Fmoc-Cys(Acm)-OH crude product；
(3) Fmoc-Cys(Acm)-OH crude product successively obtains Fmoc-Cys(Acm through extraction, acidification, washing)-OH product.
2. Fmoc-Cys(Acm according to claim 1) preparation method of-OH, which is characterized in that hydrochloric acid in step (1)
Concentration be 30-37wt%, mass ratio between hydrochloric acid, CysHCl, Acm and water is 4:(0.8-1.5): (1.6-2.4):
(3-5).
3. Fmoc-Cys(Acm according to claim 2) preparation method of-OH, which is characterized in that reaction temperature 0-10
DEG C, reaction time 18-30h.
4. Fmoc-Cys(Acm according to claim 1) preparation method of-OH, which is characterized in that in step (2), to
Acetone is added while Fmoc-OSU is added in Cys (Acm) solution；The mass ratio of acetone, Fmoc-OSU and Acm is (1.8-
2.5): (0.8-1.2): 1.
5. Fmoc-Cys(Acm according to claim 4) preparation method of-OH, which is characterized in that pH value of solution is adjusted to 7-
8。
6. Fmoc-Cys(Acm according to claim 1) preparation method of-OH, which is characterized in that in step (3),
Fmoc-Cys(Acm the mass ratio of) the extraction selection ethyl acetate of-OH crude product, ethyl acetate and Acm are 2-4:1.
7. Fmoc-Cys(Acm according to claim 6) preparation method of-OH, which is characterized in that after extraction, use concentration
Ethyl acetate layer is washed for the sodium chloride solution of 8-15wt%, is then acidified.
8. Fmoc-Cys(Acm according to claim 7) preparation method of-OH, which is characterized in that acidification use concentration for
The hydrochloric acid of 35-37wt% carries out, and is acidified to that there is no crystal precipitations；Then take crystal, it is obtained by drying after crystal pure water.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1253321A (en) * | 1968-12-19 | 1971-11-10 | Merck & Co Inc | Process for protecting mercapto groups |
| CN102321002A (en) * | 2011-06-08 | 2012-01-18 | 成都圣诺科技发展有限公司 | Cysteine derivatives as well as preparation method and application thereof |
| US8236533B2 (en) * | 2005-03-31 | 2012-08-07 | Newsouth Innovations Pty Limited | Process for the production of γ-glutamylcysteine |
| CN104744327A (en) * | 2015-01-22 | 2015-07-01 | 中国科学院合肥物质科学研究院 | Compound, preparation method thereof and method for preparing polypeptide by virtue of compound |
-
2018
- 2018-09-14 CN CN201811071173.7A patent/CN109160891A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1253321A (en) * | 1968-12-19 | 1971-11-10 | Merck & Co Inc | Process for protecting mercapto groups |
| US8236533B2 (en) * | 2005-03-31 | 2012-08-07 | Newsouth Innovations Pty Limited | Process for the production of γ-glutamylcysteine |
| CN102321002A (en) * | 2011-06-08 | 2012-01-18 | 成都圣诺科技发展有限公司 | Cysteine derivatives as well as preparation method and application thereof |
| CN104744327A (en) * | 2015-01-22 | 2015-07-01 | 中国科学院合肥物质科学研究院 | Compound, preparation method thereof and method for preparing polypeptide by virtue of compound |
Non-Patent Citations (3)
| Title |
|---|
| ALBERICIO, F. 等: "One-pot synthesis of S-acetamidomethyl-N-fluorenylmethoxycarbonyl-L- cysteine (Fmoc-Cys(Acm)-OH)", 《SYNTHESIS》 * |
| LUBELL,W.D.等: "Product class 11: Peptides", 《SCIENCE OF SYNTHESIS》 * |
| VEBER, DANIEL F.等: "Acetamidomethyl. Novel thiol protecting group for cysteine", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
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