CN108484901B - Method for preparing polylysine with high content of linear epsilon-polylysine through thermal polycondensation - Google Patents
Method for preparing polylysine with high content of linear epsilon-polylysine through thermal polycondensation Download PDFInfo
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- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
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Abstract
The invention provides a method for preparing polylysine with high content of linear epsilon-polylysine by thermal polycondensation, which belongs to the field of polymer synthesis and antibacterial materials and solves the problem of low content of linear epsilon-polylysine in branched polylysine prepared by thermal polycondensation in the prior art.
Description
Technical Field
The invention belongs to the field of polymer synthesis and antibacterial materials, and particularly relates to a method for preparing polylysine with high linear epsilon-polylysine content through thermal polycondensation.
Background
The epsilon-polylysine is cationic polyamino acid formed by connecting epsilon-amino group of a lysine monomer with α -carboxyl, is safe, nontoxic, biodegradable and has excellent antibacterial performance, and is widely applied to the fields of food preservatives, cosmetic additives and the like.
On the other hand, in recent years, there is a new situation in which the production of amino acids has been vigorously developed. Taking lysine as an example, in China alone, the annual production of lysine exceeds 200 million tons. Therefore, the search for a new polymerization method has important significance in converting renewable lysine resources into high-value-added polyamino acids.
Currently, there are still few studies related to the chemical synthesis of epsilon-polylysine. Methods for the preparation of high molecular weight epsilon-polylysines based on lactam ring-opening polymerization and specific protecting groups are provided in the literature [ chemical science,2015,6,6385-6391], [ Macromolecules,2017,50,9128-9134] and in chinese patent ZL 201510047405.5. However, the polymerization conditions are severe and complicated protection and deprotection processes are required.
The thermal polycondensation can directly take amino acid as a starting material to prepare the polyamino acid through the polycondensation between amino and carboxyl without complicated steps of monomer preparation, deprotection and the like, has the characteristics of simple operation, low cost, suitability for industrial production and the like, and is cheapAnd the renewable amino acid resources are converted into the polyamino acid with high added value. Lysine has one carboxyl group and two amino groups and belongs to AB2If the type monomer is not protected, the direct thermal polycondensation can only obtain branched polylysine, and the branched polylysine comprises three parts, namely a terminal monomer unit (T), a branched monomer unit (D) and a linear monomer unit (L), wherein the linear monomer unit comprises linear α -polylysine (L)α) And linear epsilon-polylysine (L)ε) Two parts. For example Klok et al, using lysine hydrochloride, directly to obtain hyperbranched polylysine [ Journal of Polymer Science: PartA: Polymer Chemistry,2007,45,5494-]Wherein the linear epsilon-polylysine content is about 53%. Literature [ Macromolecules,2007,40,5726-]Also reported is a process for the preparation of branched polylysine by thermal polycondensation, in which the content of linear epsilon-polylysine is only 39%. At present, the content of epsilon-polylysine in branched polylysine prepared by direct thermal polycondensation of lysine is lower.
The branched polylysine has potential application value in the fields of biomedicine, industrial production and the like. In the literature [ Macromolecular Bioscience 2012,12,794-804], studies using branched polylysine as a gene transfection reagent were reported. In the literature [ Journal of the Chemical Society, Chemical Communications1990,8-9], studies using branched polylysine as a multiple antigen peptide have been reported. In the literature [ pharmaceutical research 1998,15,776-782], a branched polylysine was synthesized and its use in drug delivery was studied. In patent CN 107349434 a, studies on magnetic resonance imaging using branched polylysine as a contrast agent carrier platform are reported. In patent CN103917623A, a study using branched polylysine as shale inhibitor is reported. However, the branched polylysine prepared by thermal polycondensation is easily subjected to excessive crosslinking, so that the solubility and the biocompatibility of the branched polylysine are poor, and the application of the branched polylysine is limited to a certain extent. On the other hand, the linear epsilon-polylysine is safe and nontoxic, has excellent antibacterial performance, improves the content of the linear epsilon-polylysine in the branched polylysine, is beneficial to improving the solubility and biocompatibility of the branched polylysine, expands the application of the branched polylysine in the fields of daily chemicals and foods, and has important industrial value. However, to our knowledge, no thermal polycondensation has been reported for the preparation of polylysine with a high linear epsilon-polylysine content, except for the preparation of linear epsilon-polylysine by ring-opening polymerization as reported in Chinese patent ZL201510047405.5 and in the literature [ Chemical Science,2015,6,6385-.
Disclosure of Invention
The invention aims to solve the problem that the linear epsilon-polylysine content in the branched polylysine prepared by thermal polycondensation in the prior art is low, and provides a method for preparing polylysine with high linear epsilon-polylysine content by thermal polycondensation.
In order to solve the technical problems, the technical scheme of the invention is as follows:
a method for preparing polylysine with high content of linear epsilon-polylysine by thermal polycondensation, which comprises the following steps:
protecting α amino group of lysine by using a dynamic protecting group to obtain a lysine monomer protected by the dynamic protecting group;
the dynamic protecting group is a protecting group which can form unstable amido bond and imine bond with α amino of lysine;
step two: and (3) grinding and uniformly mixing the lysine monomer protected by the dynamic protection group obtained in the step one with alkali, adding a catalyst at the temperature of 100-250 ℃, stirring for reacting for 1-72h, cooling to room temperature to terminate the reaction, washing, and draining to obtain the polylysine with high linear epsilon-polylysine content.
Preferably, the dynamic protecting group is selected from one or more of carbobenzoxy, tert-butoxycarbonyl, fluorenylmethyloxycarbonyl, allyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, trimethylsilethoxycarbonyl, phthaloyl, p-toluenesulfonyl, trifluoroacetyl, o- (p) -nitrobenzenesulfonyl, pivaloyl, benzoyl, benzaldehyde or isobutyraldehyde.
Preferably, the first step is specifically: adding L-lysine monohydrochloride and alkali into a reaction container, and then adding a dynamic protecting group or a compound containing the dynamic protecting group for reaction to obtain a lysine monomer protected by the dynamic protecting group;
preferably, the reaction temperature of the first step is 0-150 ℃, and the reaction time is 1-24 h.
Preferably, the alkali is one or more of sodium hydroxide, potassium hydroxide, triethylamine, potassium carbonate, sodium carbonate, concentrated ammonia water or pyridine.
Preferably, the base in the second step is one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, potassium carbonate, sodium carbonate, potassium tert-butoxide or sodium tert-butoxide.
Preferably, the molar ratio of the lysine monomer protected by the dynamic protecting group in the second step to the base is 1 (0.5-5).
Preferably, the catalyst in the second step has the following general formula:
MLx
wherein M is one or more of titanium, zirconium, hafnium, scandium, yttrium, cobalt, nickel, palladium, antimony, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, rhenium, iron, ruthenium, osmium, rhodium, iridium, gold, platinum, silver, copper, zinc, cadmium, boron, aluminum, lanthanum, samarium, cerium, neodymium or ytterbium;
l is one or more of fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, acetoxy, propionyloxy, isopropionyloxy or butanoyl; x is an integer of 1 to 6.
Preferably, the catalyst in the second step accounts for 0.05-8% of the mole fraction of the lysine monomer protected by the dynamic protecting group.
Preferably, the washing in the second step is carried out by washing with methanol, suction-filtering to remove insoluble substances, washing with water, and suction-filtering to remove insoluble substances.
The invention has the advantages of
The invention provides a method for preparing polylysine with high content of linear epsilon-polylysine by thermal polycondensation, which comprises the steps of protecting α amino groups of lysine to prepare a lysine monomer protected by a dynamic protection group, and preparing the polylysine with high content of linear epsilon-polylysine by thermal polycondensation.
Detailed Description
A method for preparing polylysine with high content of linear epsilon-polylysine by thermal polycondensation, which comprises the following steps:
protecting α amino group of lysine by using a dynamic protecting group to obtain a lysine monomer protected by the dynamic protecting group;
the dynamic protecting group is a protecting group which can form unstable amido bond and imine bond with α amino of lysine;
step two: and (3) grinding and uniformly mixing the lysine monomer protected by the dynamic protection group obtained in the step one with alkali, adding a catalyst at the temperature of 100-250 ℃, stirring for reacting for 1-72h, cooling to room temperature to terminate the reaction, washing, and draining to obtain the polylysine with high linear epsilon-polylysine content.
The dynamic protection group has the characteristic of gradually deprotecting in the thermal polycondensation process without additional deprotection operation, can form unstable amido bond and imine bond with α amino of lysine, is a protection group which is unstable to high temperature (above 100 ℃), water and strong base, is preferably a carbonyl compound, an acyl compound or an aldehyde compound, and is more preferably one or more of benzyloxycarbonyl, tert-butoxycarbonyl, fluorenylmethoxycarbonyl, allyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, trimethylethoxycarbonyl, phthaloyl silicon, p-toluenesulfonyl, trifluoroacetyl, o- (p-) nitrobenzenesulfonyl, pivaloyl, benzoyl, benzaldehyde or isobutyraldehyde.
According to the invention, firstly, L-lysine monohydrochloride and alkali are added into a reaction vessel, and then a dynamic protecting group or a compound containing the dynamic protecting group is added for reaction to obtain a lysine monomer protected by the dynamic protecting group; the compound containing the dynamic protecting group is selected conventionally according to the type and the material of the dynamic protecting group and the common knowledge of the technical personnel in the field, and is not limited in particular; the compound containing the dynamic protection group is preferably di-tert-butyl dicarbonate, benzyl chloroformate or ethyl mercaptan trifluoroacetate; when the dynamic protecting group is aldehyde, the aldehyde can be directly added for reaction, when the dynamic protecting group is carbonyl or acyl, a compound containing the dynamic protecting group is required to be added for reaction, the reaction conditions are different according to the type of the added dynamic protecting group, when the dynamic protecting group is carbonyl, the reaction temperature is preferably 0-100 ℃, more preferably 25 ℃, and the reaction time is preferably 1-24 h; when the dynamic protecting group is acyl, the reaction temperature is preferably 25-150 ℃, more preferably 25 ℃, and the reaction time is preferably 3-24 h; when the dynamic protecting group is aldehyde, the reaction temperature is preferably 0-50 ℃, more preferably 0 ℃, and the reaction time is preferably 1-12 h;
according to the invention, the alkali is one or more of sodium hydroxide, potassium hydroxide, triethylamine, potassium carbonate, sodium carbonate, concentrated ammonia water or pyridine.
According to the invention, the molar ratio of the L-lysine monohydrochloride, the base and the dynamic protective group is preferably 1 (0.5-2.5) to (1-3).
According to the invention, the obtained lysine monomer protected by the dynamic protective group and alkali are put in a mortar, ground and mixed uniformly, a catalyst is added under the condition of 100-250 ℃, stirred and reacted for 1-72h, cooled to room temperature to terminate the reaction, washed and dried to obtain the polylysine with high content of linear epsilon-polylysine. The reaction temperature of the second step is 100-250 ℃, preferably 150-200 ℃, and the time is 1-72 hours, preferably 20-48 hours; if it is less than 100 ℃ the solubility is affected, and if it is more than 250 ℃ the product is liable to crosslink, so the reaction temperature should be controlled reasonably.
According to the invention, the base in the second step is preferably one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, potassium carbonate, sodium carbonate, potassium tert-butoxide and sodium tert-butoxide.
According to the invention, the molar ratio of the lysine monomer protected by the dynamic protecting group in the second step to the base is preferably 1: 0.5-5.
According to the invention, the catalyst in the second step has the following general formula:
MLx
wherein M is one or more of titanium (Ti), zirconium (Zr), hafnium (Hf), scandium (Sc), yttrium (Y), cobalt (Co), nickel (Ni), palladium (Pd), antimony (Sb), vanadium (V), niobium (Nb), tantalum (Ta), chromium (Cr), molybdenum (Mo), tungsten (W), manganese (Mn), rhenium (Re), iron (Fe), ruthenium (Ru), osmium (Os), rhodium (Rh), iridium (Ir), gold (Au), platinum (Pt), silver (Ag), copper (Cu), zinc (Zn), cadmium (Cd), boron (B), aluminum (Al), lanthanum (La), samarium (Sm), cerium (Ce), neodymium (Nd) and ytterbium (Yb);
l is fluorine (F), chlorine (Cl), bromine (Br), iodine (I) or methyl (CH)3-, ethyl (CH)3CH2-), propyl (CH)3CH2CH2-, isopropyl ((CH)3)2CH-), butyl (CH)3CH2CH2CH2-, tert-butyl ((CH)3)3C-), methoxy (CH)3O-), ethoxy (CH)3CH2O-), propoxy (CH)3CH2CH2O-), isopropoxy ((CH)3)2CHO-), butoxy (CH)3CH2CH2CH2O-), tert-butoxy ((CH)3)3CO-), acetoxy (CH)3CH2OO-), propionic acid group (CH)3CH2CH2OO-), isopropyl acid group ((CH)3)2CHOO-), butanoyl group (CH)3CH2CH2CH2OO-; x is an integer of 1 to 6. More preferably zirconium n-butoxide (Zr (OC)4H9)4) Titanium n-butoxide (Ti (OC)4H9)4) Antimony ethoxide (Sb (OC)2H5)3) Aluminum isopropoxide (Al (OCH (CH))3)2)3) One or more of them.
According to the invention, the catalyst in the second step accounts for 0.05-8% of the mole fraction of the lysine monomer protected by the dynamic protecting group.
According to the invention, in the second step, a large amount of methanol is used for washing, suction filtration is carried out to remove insoluble substances, then a large amount of water is used for washing, and suction filtration is carried out to remove the insoluble substances.
The present invention is described in further detail below with reference to specific examples, which relate to commercially available starting materials.
Example 1
(1) α -benzaldehyde protection-preparation of lysine monomer
Adding 5g of lysine monohydrochloride into a 100mL single-neck round-bottom flask, adding 35mL of water for dissolving, adding 1.08g of sodium hydroxide, dropwise adding 2.9mL of benzaldehyde under the condition of ice-water bath, after dropwise adding, violently stirring for reacting for 2 hours, precipitating a product, performing suction filtration, removing a filtrate, washing the product with cold ethanol, and drying for 12 hours under a vacuum condition to obtain a white target product α -benzaldehyde protection-lysine monomer (4.78g, 75%).1H NMR(DMSO-d6,300MHz)δ1.19-1.31(m,2H),1.38(s,2H),1.53-1.65(m,2H),1.81-2.00(m,2H),2.66-2.72(t,2H),4.19-4.25(t,2H),7.51-7.59(m,3H),7.74-7.79(m,2H),8.67(s,1H).
(2) Preparation of polylysine with high linear epsilon-polylysine content
4.68g α -benzaldehyde protected-lysine monomer was ground with 0.8g sodium hydroxide in a mortar, and the mixture was placed in a Schlenk tube, heated to 150 deg.C, and 0.3mL zirconium butoxide (Zr (OBu))4) Stirring and reacting for 24 hours under the condition of keeping the temperature at 150 ℃, cooling to room temperature, dissolving the product in methanol, performing suction filtration, removing insoluble substances, spin-drying the filtrate, washing with water, performing vacuum drying at 50 ℃ for 12 hours to obtain a target product polylysine, and performing nuclear magnetic separationAnd (3) separating to obtain the product, wherein the content of the linear epsilon-polylysine is 83 percent.
Example 2
(1) α preparation of t-butyloxycarbonyl protected-lysine monomer
Adding 5g of lysine monohydrochloride into a 100mL single-neck round-bottom flask, adding 20mL of water for dissolving, adding 1.2g of sodium hydroxide, dropwise adding 20mL of tetrahydrofuran solution containing 3.0g of di-tert-butyl dicarbonate under the condition of ice-water bath, stirring and reacting at room temperature for 24 hours after the dropwise adding is finished, extracting after the reaction is finished, drying by spinning, and carrying out column chromatography to obtain the target product α -tert-butoxycarbonyl protected-lysine monomer (5.31g, 80%).1H NMR(D2O,300MHz)δ1.12(s,2H),1.22-1.31(m,2H),1.42(s,9H),1.47-1.60(m,2H),1.73-1.86(m,2H),2.66-2.72(t,2H),4.53-4.57(t,1H),5.49(s,1H).
(2) Preparation of polylysine with high linear epsilon-polylysine content
3.69g of α -t-butyloxycarbonyl-protected-lysine monomer was ground with 0.84g of potassium hydroxide in a mortar, and the mixture was placed in a Schlenk tube, heated to 160 ℃ and 0.2mL of titanium butoxide (Ti (OBu))4) Stirring and reacting for 20 hours under the condition of keeping at 160 ℃, cooling to room temperature, dissolving the product in methanol, performing suction filtration, removing insoluble substances, spin-drying the filtrate, washing with water, and performing vacuum drying at 50 ℃ for 12 hours to obtain a target product polylysine, wherein the content of the linear epsilon-polylysine is 85 percent through nuclear magnetic analysis.
Example 3
(1) α -preparation of carbobenzoxy protected-lysine monomer
Adding 5g of lysine monohydrochloride into a 100mL single-neck round-bottom flask, adding 20mL of water for dissolving, adding 1.5g of potassium hydroxide, dropwise adding 20mL of tetrahydrofuran solution containing 5.1g of benzyl chloroformate under the condition of ice-water bath, stirring and reacting at room temperature for 24 hours after the dropwise adding is finished, extracting after the reaction is finished, drying by spinning, and recrystallizing to obtain the target product α -benzyloxycarbonyl protection-lysine monomer (5.3g, 70%).1H NMR(D2O,300MHz)δ1.10(s,2H),1.18-1.31(m,2H),1.48-1.60(m,2H),1.74-1.84(m,2H),2.66-2.72(t,2H),4.52-4.57(t,1H),5.05(s,2H),5.52(s,1H),7.33(s,5H).
(2) Preparation of polylysine with high linear epsilon-polylysine content
4.2g α -benzyloxycarbonyl protected-lysine monomer was ground with 0.36g lithium hydroxide in a mortar, and the mixture was placed in a Schlenk tube, heated to 150 ℃ and 2mg scandium chloride (ScCl) was added3) Stirring and reacting for 30 hours under the condition of keeping the temperature at 150 ℃, cooling to room temperature, dissolving the product in methanol, performing suction filtration, removing insoluble substances, spin-drying the filtrate, washing with water, and performing vacuum drying for 12 hours at 50 ℃ to obtain a target product polylysine, wherein the content of the linear epsilon-polylysine is 82% through nuclear magnetic analysis.
Example 4
(1) α -preparation of trifluoroacetyl protected-lysine monomer
In a 100mL single-neck round-bottom flask, 5g of lysine monohydrochloride was added, 28mL (1M) of aqueous sodium hydroxide was added to dissolve the lysine monohydrochloride, 5.5mL of ethylmercaptide trifluoroacetate was added, the reaction was stirred at room temperature for 10 hours, and the product precipitated out, filtered with suction, the filtrate was removed, and recrystallized to obtain α -trifluoroacetyl protected-lysine monomer (4.6g, 70%) as a target product.1H NMR(DMSO-d6,300MHz)δ1.13(s,2H),1.18-1.31(m,2H),1.49-1.61(m,2H),1.74-1.85(m,2H),2.66-2.72(t,2H),4.53-4.57(t,1H),7.12(s,1H).
(2) Preparation of polylysine with high linear epsilon-polylysine content
3.6g α -trifluoroacetyl protected-lysine monomer was ground with 0.36g lithium hydroxide in a mortar, and the mixture was placed in a Schlenk tube, heated to 200 ℃ and 1mg triethylaluminum (Al (CH)3CH2)3) Stirring and reacting for 48 hours under the condition of keeping the temperature at 200 ℃, cooling to room temperature, dissolving the product in methanol, performing suction filtration, removing insoluble substances, spin-drying the filtrate, washing with water, and performing vacuum drying at 50 ℃ for 12 hours to obtain a target product polylysine, wherein the content of the linear epsilon-polylysine is 85 percent through nuclear magnetic analysis.
Example 5
(1) α -isobutyraldehyde protection-lysine monomer preparation
A100 mL round bottom flask was charged with 5g lysine monohydrochloride and 35 g lysine monohydrochlorideDissolving in mL of water, adding 1.08g of sodium hydroxide, dripping 2.5mL of isobutyraldehyde into the mixture under the condition of ice-water bath, after the dripping is finished, violently stirring the mixture to react for 3 hours, precipitating a product, performing suction filtration, removing filtrate, washing the product with cold ethanol, and drying the product for 12 hours under the vacuum condition to obtain a white target product α -isobutyraldehyde protection-lysine monomer (3.5g, 65%).1H NMR(DMSO-d6,300MHz)δ0.83-0.85(d,6H),1.19-1.30(m,4H),1.41-1.49(m,1H),1.56-1.71(m,3H),2.65-2.78(m,3H),4.24-4.30(t,1H),7.67-7.70(d,1H).
(2) Preparation of polylysine with high linear epsilon-polylysine content
3.0g of α -isobutyraldehyde protected-lysine monomer was ground with 0.6g of sodium hydroxide in a mortar, and the mixture was placed in a Schlenk tube, heated to 150 ℃ and then 0.2mL of zirconium butoxide (Zr (OBu))4) Stirring and reacting for 24 hours under the condition of keeping the temperature at 150 ℃, cooling to room temperature, dissolving the product in methanol, performing suction filtration, removing insoluble substances, spin-drying the filtrate, washing with water, and performing vacuum drying at 50 ℃ for 12 hours to obtain a target product polylysine, wherein the content of the linear epsilon-polylysine is 83 percent through nuclear magnetic analysis.
Example 6
(1) α preparation of t-butyloxycarbonyl protected-lysine monomer
Adding 5g of lysine monohydrochloride into a 100mL single-neck round-bottom flask, adding 20mL of water for dissolving, adding 1.2g of sodium hydroxide, dropwise adding 20mL of tetrahydrofuran solution containing 3.0g of di-tert-butyl dicarbonate under the condition of ice-water bath, stirring and reacting at room temperature for 24 hours after the dropwise adding is finished, extracting after the reaction is finished, drying by spinning, and carrying out column chromatography to obtain the target product α -tert-butoxycarbonyl protected-lysine monomer (5.31g, 80%).1H NMR(D2O,300MHz)δ1.12(s,2H),1.22-1.31(m,2H),1.42(s,9H),1.47-1.60(m,2H),1.73-1.86(m,2H),2.66-2.72(t,2H),4.53-4.57(t,1H),5.49(s,1H).
(2) Preparation of polylysine with high linear epsilon-polylysine content
3.69g of α -t-Butoxycarbonyl protected-lysine monomer was ground with 2.07g of potassium carbonate in a mortar, and the mixture was placed in a Schlenk tube, heated to 160 deg.C, and 11mg of antimony ethoxide (Sb (O)Et)3) Stirring and reacting for 30 hours under the condition of keeping at 160 ℃, cooling to room temperature, dissolving the product in methanol, performing suction filtration, removing insoluble substances, spin-drying the filtrate, washing with water, and performing vacuum drying at 50 ℃ for 12 hours to obtain a target product polylysine, wherein the content of the linear epsilon-polylysine is 85 percent through nuclear magnetic analysis.
The dynamic protecting group used in the above embodiments may be one or more of fluorenylmethyloxycarbonyl, allyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, trimethylsilethoxycarbonyl, phthaloyl, p-toluenesulfonyl, o- (p) -nitrobenzenesulfonyl, pivaloyl and benzoyl. The base used can also be one or more of sodium carbonate, potassium tert-butoxide and sodium tert-butoxide. The catalyst may be one or more of halides of metals such as hafnium (Hf), scandium (Sc), yttrium (Y), cobalt (Co), nickel (Ni), palladium (Pd), vanadium (V), niobium (Nb), tantalum (Ta), chromium (Cr), molybdenum (Mo), tungsten (W), manganese (Mn), rhenium (Re), iron (Fe), ruthenium (Ru), osmium (Os), rhodium (Rh), iridium (Ir), gold (Au), platinum (Pt), silver (Ag), copper (Cu), zinc (Zn), cadmium (Cd), boron (B), aluminum (Al), lanthanum (La), samarium (Sm), cerium (Ce), neodymium (Nd), ytterbium (Yb), and organometallic compounds thereof. Examples are not listed here.
Claims (9)
1. A method for preparing polylysine with high content of linear epsilon-polylysine by thermal polycondensation, which is characterized in that the method comprises the following steps:
protecting α amino group of lysine by using a dynamic protecting group to obtain a lysine monomer protected by the dynamic protecting group;
the dynamic protecting group is a protecting group which can form unstable amido bond and imine bond with α amino of lysine;
the dynamic protecting group is selected from one or more of carbobenzoxy, tert-butyloxycarbonyl, fluorenylmethoxycarbonyl, allyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, trimethylsiloxyethyl, phthaloyl, p-toluenesulfonyl, trifluoroacetyl, o-nitrobenzenesulfonyl, p-nitrobenzenesulfonyl, pivaloyl, benzoyl, benzaldehyde or isobutyraldehyde;
step two: and (3) grinding and uniformly mixing the lysine monomer protected by the dynamic protection group obtained in the step one with alkali, adding a catalyst at the temperature of 100-250 ℃, stirring for reacting for 1-72h, cooling to room temperature to terminate the reaction, washing, and draining to obtain the polylysine with high linear epsilon-polylysine content.
2. The method for preparing polylysine with high content of linear epsilon-polylysine by thermal polycondensation according to claim 1, wherein the first step is specifically as follows: adding L-lysine monohydrochloride and alkali into a reaction vessel, and then adding a dynamic protecting group or a compound containing the dynamic protecting group for reaction to obtain the lysine monomer protected by the dynamic protecting group.
3. The method for preparing polylysine with high content of linear epsilon-polylysine through thermal polycondensation according to claim 2, wherein the reaction temperature of the first step is 0-150 ℃, and the reaction time is 1-24 h.
4. The method for preparing polylysine having a high content of linear epsilon-polylysine through thermal polycondensation according to claim 2, wherein the base is one or more of sodium hydroxide, potassium hydroxide, triethylamine, potassium carbonate, sodium carbonate, concentrated ammonia water, or pyridine.
5. The method for preparing polylysine having a high content of linear epsilon-polylysine through thermal polycondensation according to claim 1, wherein the base in the second step is one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, potassium carbonate, sodium carbonate, potassium tert-butoxide, or sodium tert-butoxide.
6. The method for preparing polylysine with high content of linear epsilon-polylysine through thermal polycondensation according to claim 1, wherein the molar ratio of the lysine monomer protected by the dynamic protection group to the base in the second step is 1 (0.5-5).
7. The method for preparing polylysine with high content of linear epsilon-polylysine by thermal polycondensation according to claim 1, wherein the catalyst in the second step has the following general formula:
MLx
wherein M is one or more of titanium, zirconium, hafnium, scandium, yttrium, cobalt, nickel, palladium, antimony, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, rhenium, iron, ruthenium, osmium, rhodium, iridium, gold, platinum, silver, copper, zinc, cadmium, boron, aluminum, lanthanum, samarium, cerium, neodymium or ytterbium;
l is one or more of fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, acetoxy, propionyloxy, isopropionyloxy or butanoyl; x is an integer of 1 to 6.
8. The method for preparing polylysine with high content of linear epsilon-polylysine through thermal polycondensation according to claim 1, wherein the catalyst in the second step accounts for 0.05-8% of the mole fraction of the lysine monomer protected by the dynamic protection group.
9. The method for preparing polylysine with high content of linear epsilon-polylysine through thermal polycondensation according to claim 1, wherein the washing in the second step is methanol washing, suction filtration, insoluble substances removal, water washing, and suction filtration to remove insoluble substances.
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