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CN-120349288-B - Polytheanine polymerization monomer and preparation method thereof, and Polytheanine and preparation method thereof

CN120349288BCN 120349288 BCN120349288 BCN 120349288BCN-120349288-B

Abstract

The invention belongs to the technical field of polyamino acid, and provides a polymerized monomer of poly-theanine, a preparation method thereof, and poly-theanine and a preparation method thereof. The polymerized monomer of The poly-theanine with The structure shown in The formula I is theanine-N-thiocarboxylic anhydride (The-NTA), the poly-theanine can be synthesized by an NTA ring-opening polymerization method, the polymerized monomer of The poly-theanine with The structure shown in The formula II is N-phenoxycarbonyl theanine (The-NPC), and The poly-theanine can be synthesized by an NPC polymerization method. The polymerized monomer provided by the invention avoids the severe condition of synthesizing the poly (theanine) by the existing amino acid-N-carboxylic anhydride (NCA) ring-opening polymerization method, so that the condition for preparing the poly (theanine) is mild.

Inventors

  • LIU XIANGRUI
  • LIN YUANYUAN
  • WEI MENGYING
  • PENG GEGE
  • Tong Chuanye
  • LING JUN

Assignees

  • 浙江大学长三角智慧绿洲创新中心

Dates

Publication Date
20260508
Application Date
20250604

Claims (6)

  1. 1. A method for preparing theanine, which is characterized by comprising the following steps: mixing a polymerization monomer of the poly theanine, an initiator and a polar solvent, and carrying out polymerization reaction to obtain the poly theanine; the polymerized monomer of the theanine has a structure shown in a formula I: A formula I; the initiator is one or more of fatty primary amine, fatty secondary amine, benzyl amine, silicon-based amine, polyamino acid, polyether amine or polyamide; The polar solvent is a mixed solvent of acetonitrile and water, wherein the volume ratio of acetonitrile to water in the mixed solvent of acetonitrile and water is 2:1; the theanine has a structure shown in a formula III: formula III; In the formula III, R 1 is one or more of alkyl, benzyl, silicon base, polyamino acid chain, polyether chain or polyamide chain, R 2 is hydrogen, silicon base or C1-C8 alkyl, and R 3 is hydrogen.
  2. 2. The preparation method of claim 1, wherein the molar ratio of the polymerized monomer of the theanine to the initiator is 5-200:1.
  3. 3. The method according to claim 1, wherein the polymerization reaction is carried out at a temperature of 20 to 100 ℃ for a time of 0.5 to 72 hours.
  4. 4. The preparation method according to claim 1, wherein the preparation method of the structure shown in formula I comprises the following steps: mixing theanine, S-ethoxythiocarbonyl thioglycollic acid, alkali and water, and carrying out nucleophilic substitution reaction to obtain an N-ethoxythiocarbonyl theanine intermediate; The N-ethoxythiocarbonyltheanine intermediate performs a ring closure reaction under the condition of phosphorus tribromide to obtain a structure shown in a formula I.
  5. 5. The method according to claim 4, wherein the theanine is L-theanine during the nucleophilic substitution reaction, and the base comprises one or more of an inorganic base and/or an organic base; the inorganic base comprises sodium hydroxide and/or potassium hydroxide; The organic base comprises one or more of sodium alkoxide, potassium alkoxide and tetraalkylammonium hydroxide; the number of carbon atoms of the sodium alkoxide and the potassium alkoxide is independently 1-4; The number of carbon atoms of alkyl in the tetraalkylammonium hydroxide is 2-8; The molar ratio of the theanine to the S-ethoxythiocarbonylmercaptoacetic acid is 1-2:1, and the molar ratio of the theanine to the alkali is 1:2-4; The nucleophilic substitution reaction time is 12-120 h.
  6. 6. The method according to claim 4 or 5, wherein in the process of the ring closure reaction, the molar ratio of the N-ethoxythiocarbonyltheanine intermediate to the phosphorus tribromide is 1:1-3, and the time of the ring closure reaction is 0.5-24 hours.

Description

Polytheanine polymerization monomer and preparation method thereof, and Polytheanine and preparation method thereof Technical Field The invention relates to the technical field of polyamino acid, in particular to a polymerized monomer of poly-theanine and a preparation method thereof, and poly-theanine and a preparation method thereof. Background Poly (alpha-amino acid) s, PAA is a macromolecular compound formed by connecting amino acids as repeated units through peptide bonds, and has excellent biocompatibility and biodegradability. The PAA has rich physical and chemical properties due to the rich structure of the side group R group. For example, polylysine (PLys) and polyglutamic acid (PGlu) are pH-responsive, polyalanine (PAla) and phenylalanine (PPhe) exhibit oil solubility, while polyserine (PSer) and polymorpholine (PSar) have good water solubility. By virtue of the unique properties, the PAA has wide application prospect in the biomedical fields such as drug delivery, gene transfection, biosensors, tissue engineering and the like. The current chemical synthesis method of the polyamino acid mainly comprises a solid phase synthesis method (mainly used for oligopeptide synthesis), an amino acid-N-carboxylic anhydride (NCA) ring-opening polymerization method, an amino acid-N-thiocarboxylic anhydride (NTA) ring-opening polymerization method and an N-phenoxycarbonyl amino acid (NPC) polymerization method. Theanine (N-ethyl-gamma-glutamine) has the following structure: 。 Theanine, which is a derivative of glutamine, is a natural non-protein amino acid that is widely found in tea leaves. Researches show that theanine has various physiological activities of neuroprotection, fatigue resistance, tumor resistance, blood pressure reduction and the like, and has important application value in the fields of food, medicine, chemical industry and the like. Polytheanine (PThe) is a type of polyamino acid containing amide groups in its side chains, and the current research on its synthesis and application is still in the preliminary stage. Currently, there are researchers attempting to prepare theanine by electrochemical polymerization, but not successfully isolating the target product for systematic characterization of its structure and properties (j. Electroanal. Chem., 2013, 709, 1-9). In the same year, researchers have proposed a new method of directly synthesizing amino acid-N-carboxylic anhydride NCA monomers from amino acids containing amide groups such as theanine and preparing the corresponding polyamino acids by ring-opening polymerization (Japanese patent JP 2013-234207A 2013.11.21), but NCA monomers are extremely high in reactivity, and strict anhydrous and anaerobic conditions are required in the processes of synthesizing, purifying, preserving and forming the poly-theanine by utilizing the polymerization reaction, so that the feasibility of mass production of the poly-theanine is greatly limited. Disclosure of Invention In view of the above, the present invention aims to provide a polymerized monomer of theanine and a preparation method thereof, and a polymerized monomer of theanine and a preparation method thereof. The polymerized monomer provided by the invention can make the conditions of the preparation method of the poly theanine mild. In order to achieve the above object, the present invention provides the following technical solutions: the invention provides a polymerized monomer of theanine, which has a structure shown in a formula I or a formula II: The compound of the formula I, Formula II. The invention also provides a preparation method of the polymerized monomer of the theanine, which is characterized in that the preparation method of the structure shown in the formula I comprises the following steps: mixing theanine, S-ethoxythiocarbonyl thioglycollic acid, alkali and water, and carrying out nucleophilic substitution reaction to obtain an N-ethoxythiocarbonyl theanine intermediate; The N-ethoxythiocarbonyltheanine intermediate performs a ring closure reaction under the condition of phosphorus tribromide to obtain a structure shown in a formula I; The preparation method of the structure shown in the formula II comprises the following steps: The theanine, phenyl chloroformate and sodium bicarbonate undergo an elimination reaction in a two-phase mixed solvent to obtain a structure shown in a formula II, wherein the two-phase mixed solvent comprises water and an organic solvent. Preferably, during the nucleophilic substitution reaction, the theanine is L-theanine, and the base comprises one or more of inorganic base and/or organic base; the inorganic base comprises sodium hydroxide and/or potassium hydroxide; the organic base includes one or more of sodium alkoxide, potassium alkoxide, and tetraalkylammonium hydroxide; the number of carbon atoms of the sodium alkoxide and the potassium alkoxide is independently 1-4; The number of carbon atoms of alkyl in the tetraalkylammonium hydroxide is 2-8;