CN116891417A - Synthesis method of N, N-bis (carboxymethyl) -L-lysine - Google Patents

Synthesis method of N, N-bis (carboxymethyl) -L-lysine Download PDF

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CN116891417A
CN116891417A CN202311165278.XA CN202311165278A CN116891417A CN 116891417 A CN116891417 A CN 116891417A CN 202311165278 A CN202311165278 A CN 202311165278A CN 116891417 A CN116891417 A CN 116891417A
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lysine
bis
carboxymethyl
stirring
sodium
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张翔鸿
程悦
张卓
赵林吉
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Chengdu Aoke New Technology Co ltd
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Chengdu Aoke New Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
    • C07C227/20—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters by hydrolysis of N-acylated amino-acids or derivatives thereof, e.g. hydrolysis of carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention discloses a method for synthesizing N, N-bis (carboxymethyl) -L-lysine, which relates to the technical field of NTA intermediate synthesis and comprises the steps of S1, L-lysine is chelated by copper ions, boc is introduced to protect N6, and then copper ions are removed to obtain N6- (tert-butoxycarbonyl) -L-lysine; s2, N2-N6- (tert-butoxycarbonyl) -L-lysine reacts with two molecules of bromoacetic acid in alkaline aqueous solution to prepare N2, N2-bis (carboxymethyl) -N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine; s3, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethyl ethoxy) carbonyl ] -L-lysine is decomposed into tert-butoxycarbonyl by an acid system, N-bis (carboxymethyl) -L-lysine is dissociated by alkali, and the product is obtained by crystallization. The scheme is safe, efficient, cheap and suitable for mass industrialized production.

Description

Synthesis method of N, N-bis (carboxymethyl) -L-lysine
Technical Field
The invention relates to the technical field of NTA intermediate synthesis, in particular to a method for synthesizing N, N-bis (carboxymethyl) -L-lysine.
Background
In order to increase the water solubility of the drug carrier, it is generally employed to chelate NTA (short for aminotriacetic acid) having high water solubility on metal nanoparticles or to graft NTA on micelle block copolymers. N, N-bis (carboxymethyl) -L-lysine is a main raw material for NTA production, and regarding the synthesis of N, N-bis (carboxymethyl) -L-lysine, the prior art has the following drawbacks:
(1) the method adopts sodium azide to react in DMF at 75 ℃ to obtain N, N-bis (carboxymethyl) -L-lysine in the condition of severe reaction conditions and poor safety, and is not suitable for mass production;
(2) org.biomol.chem. [ J ],2010,8,3902_3907 using n6_cbz_l-lysine with bromoacetic acid, and then hydrogenation to give N, N-bis (carboxymethyl) -L-lysine with a product yield of 50%; bromoacetic acid is easy to decompose under the condition of strong alkali, and the bromoacetic acid is added into the strong alkali solution first, so that the use amount of bromoacetic acid can be increased, the yield of the product is reduced, and the cost is increased;
(3) publication number CN108586291a discloses a process for producing N, N-bis (carboxymethyl) -L-lysine, which uses expensive palladium reagents to react in an autoclave, and only 10kg of product per 1000L of production volume per single batch is produced due to the solubility problem of intermediates, which has failed to meet the increasing market demand; the yield of the process is further reduced in the process of amplifying production, a large amount of waste is generated, and the process is not beneficial to industrial production.
Disclosure of Invention
In order to solve the defects in the prior art, the invention provides a method for synthesizing N, N-bis (carboxymethyl) -L-lysine, which is safe, efficient, cheap and suitable for mass industrialized production.
In order to achieve the object of the invention, the following scheme is adopted:
a synthesis method of N, N-bis (carboxymethyl) -L-lysine comprises the following reaction processes:
the method comprises the steps of carrying out a first treatment on the surface of the The synthesis method comprises the following stepsThe steps are as follows:
s1, L-lysine is chelated by copper ions, and Boc is introduced to protect N6, thus obtaining bis [ N6- [ (1, 1-dimethylethoxy) carbonyl group]L-lysine-KN 2, KO1]Copper, wherein Boc is an abbreviation for tert-butoxycarbonyl, is an amino protecting group, boc 2 o is an abbreviation for di-tert-butyl dicarbonate, used in the formula to provide the Boc group; bis [ N6- [ (1, 1-dimethylethoxy) carbonyl ]]L-lysine-KN 2, KO1]Copper ions are removed from copper to obtain N6- (tert-butoxycarbonyl) -L-lysine;
s2, N2-N6- (tert-butoxycarbonyl) -L-lysine reacts with two molecules of bromoacetic acid in alkaline aqueous solution to prepare N2, N2-bis (carboxymethyl) -N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine;
s3, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethyl ethoxy) carbonyl ] -L-lysine is decomposed into tert-butoxycarbonyl by an acid system, N-bis (carboxymethyl) -L-lysine is dissociated by alkali, and the product is obtained by crystallization.
Further, step S1 includes: adding L-lysine and water into a container, adding copper sulfate under stirring, stirring at room temperature for several hours, adding acetone and Boc 2 o, alkali, stirring at room temperature for reaction overnight, precipitating a large amount of blue solid, adding the blue solid into water after filtering, adding a reagent for removing copper ions, precipitating a large amount of solid, and filtering to obtain N6- (tert-butoxycarbonyl) -L-lysine.
Further, in step S1, the base used when Boc is introduced is one or more of sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, and diisopropylethylamine.
In step S1, the reagent for removing copper ions is one or more of EDTA (ethylenediamine tetraacetic acid), sodium sulfide, and potassium sulfide.
Further, in step S2, bromoacetic acid is replaced with one or more of chloroacetic acid, sodium bromoacetate, sodium chloroacetate, potassium bromoacetate, and potassium chloroacetate.
Further, in step S2, the alkaline aqueous solution is one or more of sodium hydroxide, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, diisopropylethylamine, LDA (lithium diisopropylamide), liHMDS (lithium hexamethyldisilazide).
Further, step S2 includes: adding N6- (tert-butoxycarbonyl) -L-lysine into sodium hydroxide solution, stirring and dissolving; adding bromoacetic acid into a container, adding sodium hydroxide solution, cooling to 0-5 ℃, dropwise adding standby N6- (tert-butoxycarbonyl) -L-lysine solution, and stirring for several hours at 0-5 ℃ after the dropwise adding; heating to 45-55 deg.c and stirring for several hr; cooling the system to 0-5 ℃, adding ethyl acetate, dropwise adding hydrochloric acid to adjust the pH value to 1.5-2.5, and keeping the temperature at 15 ℃ in the dropwise adding process; and (3) carrying out layered extraction on the dripping, drying anhydrous sodium sulphate, concentrating to dryness, adding petroleum ether, pulping, filtering to obtain white solid, and drying.
In step S3, the acidic system is one or more of trifluoroacetic acid, hydrochloric acid, ethyl acetate hydrogen chloride, ethanol hydrogen chloride, methanol hydrogen chloride, tetrahydrofuran hydrogen chloride, p-toluenesulfonic acid, acetic acid, bromoacetic acid, chloroacetic acid, and pure water.
Further, in step S3, the base used is one or more of sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, and diisopropylethylamine.
Further, step S3 includes: adding dichloromethane into a container, adding N2, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethyl ethoxy) carbonyl ] -L-lysine and trifluoroacetic acid under stirring, stirring for reaction overnight, separating out solid, filtering, vacuum drying the collected solid, adding into methanol, adding triethylamine under stirring, controlling the temperature to 50-65 ℃, dissolving the system, stirring for a plurality of hours, cooling to 0-25 ℃, stirring for a plurality of hours, separating out a large amount of solid, filtering, flushing with methanol, and drying.
The invention has the beneficial effects that: the L-lysine is used as a starting material, boc is used for protecting N6 amino, expensive palladium reagent is avoided, the whole cost is low, a dangerous autoclave is avoided in the reaction process, and the reaction process is safer; the synthesis method is completed in three steps, is simple and convenient to operate, has high product yield, and is more suitable for industrial production.
Detailed Description
N, N-bis (carboxymethyl) -L-lysine having the formula:
。
the embodiment provides a synthesis method for synthesizing the N, N-bis (carboxymethyl) -L-lysine, which comprises the following steps:
s1, preparing N6- (tert-butoxycarbonyl) -L-lysine by using L-lysine;
s11 and L-lysine are chelated by copper ions, and Boc is introduced to protect N6, so that bis [ N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine-KN 2, KO1] copper is obtained, and the reaction formula is as follows:
。
s12, removing copper ions from bis [ N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine-KN 2, KO1] copper to obtain N6- (tert-butoxycarbonyl) -L-lysine, wherein the reaction formula is as follows:
。
the specific method for preparing the N6- (tert-butoxycarbonyl) -L-lysine comprises the following steps: adding L-lysine and water into a container, adding copper sulfate under stirring, stirring at room temperature for several hours, adding acetone and Boc 2 o, alkali, stirring at room temperature for reaction overnight, precipitating a large amount of blue solid, adding the blue solid into water after filtering, adding a reagent for removing copper ions, precipitating a large amount of solid, and filtering to obtain N6- (tert-butoxycarbonyl) -L-lysine.
Wherein, the alkali used when introducing Boc is one or more of sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine and diisopropylethylamine; the reagent for removing copper ions adopts one or more of EDTA, sodium sulfide and potassium sulfide.
S2, N2-bis (carboxymethyl) -N6- [ (1, 1-dimethyl ethoxy) carbonyl ] -L-lysine is prepared by reacting N2 amino group of N6- (tert-butoxycarbonyl) -L-lysine with two molecules of bromoacetic acid in alkaline aqueous solution, wherein the reaction formula is as follows:
。
the specific method for preparing N2, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine comprises the following steps: adding N6- (tert-butoxycarbonyl) -L-lysine into sodium hydroxide solution, stirring and dissolving; adding bromoacetic acid into a container, adding sodium hydroxide solution, cooling to 0-5 ℃, dropwise adding the N6- (tert-butoxycarbonyl) -L-lysine solution prepared in the previous step, and stirring for several hours at 0-5 ℃ after the dropwise adding; heating to 45-55 deg.c and stirring for several hr; cooling the system to 0-5 ℃, adding ethyl acetate, dropwise adding hydrochloric acid to adjust the pH value to 1.5-2.5, and keeping the temperature at 15 ℃ in the dropwise adding process; and (3) carrying out layered extraction on the dripping, drying anhydrous sodium sulphate, concentrating to dryness, adding petroleum ether, pulping, filtering to obtain white solid, and drying.
Wherein, the bromoacetic acid is used for giving carboxymethyl on N2, and the bromoacetic acid can be replaced by one or more of chloroacetic acid, sodium bromoacetate, sodium chloroacetate, potassium bromoacetate and potassium chloroacetate. The alkaline aqueous solution is sodium hydroxide, and can be replaced by one or more of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, diisopropylethylamine, LDA and LiHMDS.
S3, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethyl ethoxy) carbonyl ] -L-lysine is decomposed into tert-butoxycarbonyl by an acid system, N-bis (carboxymethyl) -L-lysine is dissociated by alkali, and the product is obtained by crystallization, wherein the reaction formula is as follows:
。
the specific preparation method of the N, N-bis (carboxymethyl) -L-lysine comprises the following steps: adding dichloromethane into a container, adding N2, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethyl ethoxy) carbonyl ] -L-lysine and trifluoroacetic acid under stirring, stirring for reaction overnight, separating out solid, filtering, vacuum drying the collected solid, adding into methanol, adding triethylamine under stirring, controlling the temperature to 50-65 ℃, dissolving the system, stirring for a plurality of hours, cooling to 0-25 ℃, stirring for a plurality of hours, separating out a large amount of solid, filtering, flushing with methanol, and drying.
Wherein the acidic system is trifluoroacetic acid, and can be replaced by one or more of ethyl acetate hydrogen chloride, hydrochloric acid, ethanol hydrogen chloride, methanol hydrogen chloride, tetrahydrofuran hydrogen chloride, p-toluenesulfonic acid, acetic acid, bromoacetic acid, chloroacetic acid and pure water. The base is triethylamine, and can be replaced by one or more of sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium hydroxide and diisopropylethylamine. The solvent used in the desalting process is methanol, and can be replaced by one or more of deionized water, ethanol, isopropanol, tetrahydrofuran, acetonitrile, ethyl acetate and isopropyl acetate.
Example 1
S1, preparing N6- (tert-butoxycarbonyl) -L-lysine: l-lysine (14.6 g,1.0 eq.) was added to a 500ml three-necked flask, 150ml of water was added to the flask, and anhydrous copper sulfate (12.5 g,0.5 eq.) was added with stirring, and the mixture was stirred at room temperature for 4 hours, and acetone 15ml and Boc were added 2 o (24 g,1.1 eq), sodium bicarbonate (16.8 g,2 eq), stirring at room temperature overnight, precipitating a large amount of blue solid, filtering, adding the solid to 100ml of water, adding sodium sulphide (3.9 g,0.5 eq), precipitating a large amount of black solid, filtering, collecting the filtrate, adjusting the pH to neutrality, cooling to precipitate white solid, obtaining the product N6- (tert-butoxycarbonyl) -L-lysine.
S2, preparation of N2, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine: n6- (t-Butoxycarbonyl) -L-lysine (24.6 g,1.0 eq.) was added to 2M sodium hydroxide solution (110 mL,2.20 eq.) and the solution was stirred for further use; in a 500mL three-necked flask, bromoacetic acid (27.8 g,2.0 equivalents) was added, 2M sodium hydroxide solution (150 mL,3.0 equivalents) was added, the temperature was lowered to 0 ℃, the prepared N6- (tert-butoxycarbonyl) -L-lysine solution was dropwise added, after the dropwise addition, the mixture was stirred at 0℃for 2 hours, and the temperature was raised to 50℃and stirred for 6 hours; the system is cooled to 0 ℃, 150ml of ethyl acetate is added, 6N hydrochloric acid is added dropwise to adjust the pH value to 2, the internal temperature is kept not to exceed 15 ℃ in the dripping process, the dripping process is carried out after layered extraction, anhydrous sodium sulphate is dried, concentrated to dryness, white solid is obtained, 31.9g of product is obtained after drying, and the yield is 88%.
S3, preparing N, N-bis (carboxymethyl) -L-lysine: to a 250ml three-necked flask, 120ml of a 2M ethyl acetate hydrogen chloride solution was added, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine (36.2 g,1.0 eq) was added with stirring, the reaction was stirred overnight, solids were precipitated, filtered, the collected solids were dried in vacuo and then added to 150ml of deionized water, sodium hydroxide (4 g,1.0 eq) was added with stirring, the internal temperature was controlled to 60℃and the system was allowed to dissolve for 1h, and then cooled to 0℃and stirred for 2h to precipitate a large amount of solids, which were filtered, rinsed with deionized water and dried to give 23.6g of product with a yield of 90%.
Example 2
S1, preparing N6- (tert-butoxycarbonyl) -L-lysine: l-lysine (14.6 g,1.0 eq.) was added to a 500ml three-necked flask, 150ml of water was added to the flask, anhydrous copper sulfate (12.5 g,0.5 eq.) was added with stirring, and the reaction was stirred at room temperature for 4 hours, acetone 15ml and Boc were added 2 o (24 g,1.1 eq), sodium bicarbonate (16.8 g,2 eq), stirring at room temperature overnight, precipitating a large amount of blue solid, filtering, adding the solid to 100ml of water, adding sodium sulfide (3.9 g,0.5 eq), precipitating a large amount of black solid, filtering, collecting the filtrate, adjusting the pH to neutrality, cooling to precipitate black solid, and obtaining the product N6- (tert-butoxycarbonyl) -L-lysine.
Step 2, preparation of N2, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine: n6- (t-Butoxycarbonyl) -L-lysine (24.6 g,1.0 eq.) was added to 2M sodium hydroxide solution (110 mL,2.20 eq.) and the solution was stirred for further use; in a 500mL three-necked flask, bromoacetic acid (41.7 g,3.0 eq) was added, 2M sodium hydroxide solution (200 mL,4.0 eq) was added, the temperature was lowered to 0 ℃, the prepared L-Lys (Boc) solution was added dropwise, the mixture was stirred at 0℃for 2 hours, and the temperature was raised to 50℃and stirred for 6 hours; the system is cooled to 0 ℃, 150ml of ethyl acetate is added, 6N hydrochloric acid is added dropwise to adjust the pH value to 2, the internal temperature is kept not to exceed 15 ℃ in the dripping process, the dripping process is carried out after layering extraction, anhydrous sodium sulphate is dried, concentrated to dryness, petroleum ether is added for pulping, filtration is carried out, white solid is obtained, and the product is obtained by drying, wherein the yield is 32.6 g.
S3, preparing N, N-bis (carboxymethyl) -L-lysine: into a 500ml three-necked flask, 150ml of methylene chloride was added, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine (36.2 g,1.0 equivalent) was added under stirring, 50ml of trifluoroacetic acid was reacted overnight under stirring, solids were precipitated, the collected solids were dried under vacuum and then added to 200ml of methanol, triethylamine (10.1 g,1.0 equivalent) was added under stirring at an internal temperature of 50℃and then slowly cooled to 25℃after the addition, a large amount of solids was precipitated under stirring for 1 hour, and the mixture was filtered, washed with methanol and dried to give 24.1g of a product with a yield of 92%.
In summary, the synthesis method of the embodiment uses L-lysine as a starting material, adopts Boc to protect N6 amino, avoids using expensive palladium reagent, has low overall cost, avoids using a dangerous autoclave in the reaction process, and ensures safer reaction process; the synthesis method is completed in three steps, is simple and convenient to operate, has high yield of N, N-bis (carboxymethyl) -L-lysine products, and is more suitable for industrial production.
The above embodiments are merely for illustrating the technical ideas and features of the present invention, and are not meant to be exclusive or limiting. It will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention.

Claims (10)

1. A method for synthesizing N, N-bis (carboxymethyl) -L-lysine, which is characterized by comprising the following steps:
s1, chelating L-lysine through copper ions, and introducing Boc to protect N6 to obtain bis [ N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine-KN 2, KO1] copper; removing copper ions to obtain N6- (tert-butoxycarbonyl) -L-lysine;
s2, N2-N6- (tert-butoxycarbonyl) -L-lysine reacts with two molecules of bromoacetic acid in alkaline aqueous solution to prepare N2, N2-bis (carboxymethyl) -N6- [ (1, 1-dimethylethoxy) carbonyl ] -L-lysine;
s3, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethyl ethoxy) carbonyl ] -L-lysine is decomposed into tert-butoxycarbonyl by an acid system, N-bis (carboxymethyl) -L-lysine is dissociated by alkali, and the product is obtained by crystallization;
the reaction process is as follows:
。
2. the method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 1, wherein step S1 comprises: adding L-lysine and water into a container, adding copper sulfate under stirring, stirring at room temperature for several hours, adding acetone and Boc 2 o, alkali, stirring at room temperature for reaction overnight, precipitating a large amount of blue solid, adding the blue solid into water after filtering, adding a reagent for removing copper ions, precipitating a large amount of solid, and filtering to obtain N6- (tert-butoxycarbonyl) -L-lysine.
3. The method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 2, wherein in the step S1, the base used in introducing Boc is one or more of sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, diisopropylethylamine.
4. The method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 1, wherein in the step S1, one or more of EDTA, sodium sulfide and potassium sulfide are used as the reagent for removing copper ions.
5. The method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 1, wherein in step S2, bromoacetic acid is replaced with one or more of chloroacetic acid, sodium bromoacetate, sodium chloroacetate, potassium bromoacetate, potassium chloroacetate.
6. The method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 1, wherein in step S2, the alkaline aqueous solution is one or more of sodium hydroxide, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, diisopropylethylamine, LDA, liHMDS.
7. The method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 1, wherein step S2 comprises: adding N6- (tert-butoxycarbonyl) -L-lysine into sodium hydroxide solution, stirring and dissolving; adding bromoacetic acid into a container, adding sodium hydroxide solution, cooling to 0-5 ℃, dropwise adding standby N6- (tert-butoxycarbonyl) -L-lysine solution, and stirring for several hours at 0-5 ℃ after the dropwise adding; heating to 45-55 deg.c and stirring for several hr; cooling the system to 0-5 ℃, adding ethyl acetate, dropwise adding hydrochloric acid to adjust the pH value to 1.5-2.5, and keeping the temperature at 15 ℃ in the dropwise adding process; and (3) carrying out layered extraction on the dripping, drying anhydrous sodium sulphate, concentrating to dryness, adding petroleum ether, pulping, filtering to obtain white solid, and drying.
8. The method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 1, wherein in the step S3, the acidic system is one or more of trifluoroacetic acid, hydrochloric acid, ethyl acetate hydrogen chloride, ethanol hydrogen chloride, methanol hydrogen chloride, tetrahydrofuran hydrogen chloride, p-toluenesulfonic acid, acetic acid, bromoacetic acid, chloroacetic acid, and pure water.
9. The method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 1, wherein the base is one or more of sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, triethylamine, and diisopropylethylamine.
10. The method for synthesizing N, N-bis (carboxymethyl) -L-lysine according to claim 1, wherein step S3 comprises: adding dichloromethane into a container, adding N2, N2 bis (carboxymethyl) -N6- [ (1, 1-dimethyl ethoxy) carbonyl ] -L-lysine and trifluoroacetic acid under stirring, stirring for reaction overnight, separating out solid, filtering, vacuum drying the collected solid, adding into methanol, adding triethylamine under stirring, controlling the temperature to 50-65 ℃, dissolving the system, stirring for a plurality of hours, cooling to 0-25 ℃, stirring for a plurality of hours, separating out a large amount of solid, filtering, flushing with methanol, and drying.
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