CN118108794A - Synthesis method of flaxseed cyclic peptide - Google Patents

Synthesis method of flaxseed cyclic peptide Download PDF

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Publication number
CN118108794A
CN118108794A CN202410344725.6A CN202410344725A CN118108794A CN 118108794 A CN118108794 A CN 118108794A CN 202410344725 A CN202410344725 A CN 202410344725A CN 118108794 A CN118108794 A CN 118108794A
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compound
flaxseed
formula
reaction
cyclic peptide
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姬胜利
郭凯
张文杰
董玉香
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Reali Tide Biological Technology Weihai Co ltd
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Reali Tide Biological Technology Weihai Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64—Cyclic peptides containing only normal peptide links

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Abstract

The invention belongs to the technical field of biological medicines, and relates to a synthesis method of flaxseed cyclic peptides. In the synthesis method, the compound shown in the formula I or the compound shown in the formula III is prepared first,

Description

Synthesis method of flaxseed cyclic peptide
Technical Field
The invention belongs to the technical field of biological medicines, and relates to a synthesis method of flaxseed cyclic peptides.
Background
The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art.
The semen Lini cyclic peptide has immunoregulatory, antimalarial, antifungal, antiinflammatory, and anticancer activities; meanwhile, the modified starch can be used as a core component of an anti-aging medical product. The main components of the flaxseed cyclic peptide are flaxseed cyclic peptide A (CAS# is 33302-55-5, molecular formula: C 57H85N9O9, molecular weight: 1040.36) and flaxseed cyclic peptide B (CAS# is 193139-41-2, molecular formula: C 56H83N9O9 S, molecular weight: 1058.39), the contents are 30-40% and 25-35% respectively.
The current method for obtaining the flaxseed cyclic peptide mainly comprises the steps of extraction, complex process and raw material limitation. The synthesis method is less studied, and as the end-to-end cyclic peptide, the classical method is to selectively activate and cyclize the protected linear precursor in a highly diluted solution, the reaction is relatively slow, and meanwhile, the method still has a large proportion of side reactions such as dimerization, polymerization and the like, and has low synthesis yield and uses a large amount of solvent. The solid phase method can effectively avoid side reactions such as dimerization, polymerization and the like in the cyclization process. The limitation of this approach is that the linear polypeptide precursors must contain lysine, aspartic acid or asparagine, glutamic acid or glutamine, etc., and the synthesis of flaxseed cyclic peptides is not possible using this approach. Patent CN110551178B discloses a preparation method of a proline-containing head-tail cyclopeptide synthesis method, which can be applied to the synthesis of pseudostellaria root cyclopeptide B, but the inventor researches find that the method needs to use specially protected proline: fmoc-3-carboxyl-Pro-OAll, the expensive reagent tetra-triphenylphosphine palladium is needed for removing OALL, the solid-phase polypeptide synthesis process is a heterogeneous reaction, at least twice of the equivalent of amino acid raw materials are needed, a large amount of solvents are needed for washing the resin, and the reaction process cannot be detected and judged to be complete or generate impurities by a TLC method.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide a synthesis method of flaxseed cyclic peptide, which not only can effectively avoid side reactions such as dimerization and multimerization in the cyclization process, but also can overcome the problems of using a large amount of harmful solvents and the like for solid-phase polypeptides, and can also reduce the consumption of raw materials and solvents.
In order to achieve the above purpose, the technical scheme of the invention is as follows:
in a first aspect, a polypeptide structural compound with a hydrophobic carrier, the chemical structural formula of which is shown in a formula I,
In a second aspect, a polypeptide structural compound with a hydrophobic carrier, the chemical structure of which is shown in a formula III,
In a third aspect, the use of a polypeptide structural compound with a hydrophobic carrier according to the first or second aspect for the preparation of a flaxseed cyclic peptide.
In a fourth aspect, a method for synthesizing flaxseed cyclic peptide, comprising the steps of synthesizing flaxseed cyclic peptide A and/or synthesizing flaxseed cyclic peptide B;
The synthesis process of the flaxseed cyclic peptide A comprises the following steps: synthesizing a compound shown in a formula I from 3,4, 5-trioctadecyl phenyl formaldehyde and an amino acid raw material, performing intramolecular amide cyclization reaction on the compound shown in the formula I to obtain a compound shown in a formula II, and removing 3,4, 5-trioctadecyl benzyl in the compound shown in the formula II to obtain flaxseed cyclopeptide A;
The synthesis process of the flaxseed cyclic peptide B comprises the following steps: synthesizing a compound shown in a formula III from 3,4, 5-trioctadecyl phenyl formaldehyde and an amino acid raw material, performing intramolecular amide cyclization reaction on the compound shown in the formula III to obtain a compound shown in a formula IV, and removing 3,4, 5-trioctadecyl benzyl in the compound shown in the formula IV to obtain flaxseed cyclopeptide B;
The beneficial effects of the invention are as follows:
The invention synthesizes flaxseed cyclic peptide by using a hydrophobic carrier 'molecular claw' method, and the method has the advantage of carrying out cyclization on resin to synthesize the pseudo dilution in the cyclic peptide, thereby being beneficial to the intermolecular reaction. The amide cyclization reaction is a two-phase reaction, the peptide chain-linking part is carried out in acetonitrile solution, and the hydrophobic carrier is an insoluble part, so that intermolecular coupling can be effectively blocked, and side reactions such as dimerization, multimerization and the like in the cyclization process are effectively avoided. Because solid phase synthesis is a heterogeneous reaction, at least twice as much amino acid starting material is required to be consumed, and a large amount of solvent is required to wash the resin. The method adopts a homogeneous reaction system in the amino acid coupling reaction process, avoids the problems of poor atom economy, high production cost and the like caused by excessive amino acid equivalent and washing of a large amount of solvents, and reduces the consumption of raw materials and solvents.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 is a schematic diagram showing the synthesis of Linseed cyclopeptide A of example 1 of the present invention;
FIG. 2 is a mass spectrum of a compound of the synthetic structure I in example 1 of the present invention;
FIG. 3 is a mass spectrum of the synthetic flaxseed cyclopeptide A of example 1 of the present invention;
FIG. 4 is a schematic diagram showing the synthesis of Linseed cyclopeptide B of example 2 of the present invention;
FIG. 5 is a mass spectrum of a compound of the synthetic structure III in example 2 of the present invention;
FIG. 6 is a mass spectrum of the synthetic flaxseed cyclopeptide B of example 2 of the present invention.
Detailed Description
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present invention. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
The english abbreviations of the substances appearing in the present invention correspond to chinese meanings as shown in the table below:
in view of the problems of side reaction, low yield and high consumption of solvent and amino acid raw materials in the existing chemical synthesis method of the linseed cyclopeptide, the invention provides a synthesis method of the linseed cyclopeptide.
In one exemplary embodiment of the invention, a polypeptide structural compound with a hydrophobic carrier is provided, the chemical structural formula of the polypeptide structural compound is shown as a formula I,
In another exemplary embodiment of the present invention, a polypeptide structural compound with a hydrophobic carrier is provided, the chemical structure of which is shown in formula III,
In a third exemplary embodiment of the present invention, an application of the polypeptide structure compound with a hydrophobic carrier in preparing flaxseed cyclic peptides is provided.
In some embodiments, the polypeptide structural compound with the hydrophobic carrier is subjected to intramolecular amide cyclization reaction to obtain a cyclopeptide compound with the hydrophobic carrier, and the hydrophobic carrier in the cyclopeptide compound with the hydrophobic carrier is removed to obtain the cyclopeptide compound;
Wherein the cyclopeptide compound with the hydrophobic carrier is a compound shown in a formula II or a compound shown in a formula IV,
The cyclic peptide compound is
Specifically, the reaction system of the amide cyclization reaction is a suspension. The amide cyclization reaction is to carry out amidation reaction on amino and carboxyl to form an amide bond so as to enable the polypeptide to form cyclic peptide, thereby completing cyclization.
Meanwhile, since the amidation reaction is a dehydration condensation reaction of an amino group with a carboxyl group to form an amide bond, the amidation reaction is also a condensation reaction. Specifically, the condensing agent for the amide cyclization reaction comprises one or more of EDC-HCl, oxyma and sodium bicarbonate.
Specifically, the reaction temperature of the amide cyclization reaction is 20-30 ℃ and the reaction time is 70-74 hours.
Specifically, the solvent for the amide cyclization reaction is dichloromethane, methyltetrahydrofuran, or acetonitrile.
Specifically, the process of removing the hydrophobic carrier is as follows: the cyclic peptide compound with the hydrophobic carrier is subjected to a removal reaction under the condition of adding trifluoroacetic acid. More specifically, the temperature of the removal reaction is 20-30 ℃ and the time is 3-5 hours.
Specifically, after the hydrophobic carrier is removed, the reacted slurry is filtered, and the filtered filtrate is concentrated, precipitated by methyl tertiary butyl ether, filtered and dried to obtain a crude product. More specifically, the crude product is purified by a reversed-phase high-performance liquid chromatography. Further, the mobile phase A in the reversed-phase high-performance liquid chromatography is trifluoroacetic acid/water solution, and the mobile phase B is trifluoroacetic acid/acetonitrile solution. The concentration of trifluoroacetic acid in the trifluoroacetic acid/water solution is 0.09-0.11%. The concentration of trifluoroacetic acid in the trifluoroacetic acid/acetonitrile solution is 0.09-0.11%.
In a fourth exemplary embodiment of the present invention, there is provided a method for synthesizing a flaxseed cyclic peptide, comprising the steps of synthesizing a flaxseed cyclic peptide a or/and synthesizing a flaxseed cyclic peptide B;
The synthesis process of the flaxseed cyclic peptide A comprises the following steps: synthesizing a compound shown in a formula I from 3,4, 5-trioctadecyl phenyl formaldehyde and an amino acid raw material, performing intramolecular amide cyclization reaction on the compound shown in the formula I to obtain a compound shown in a formula II, and removing 3,4, 5-trioctadecyl benzyl in the compound shown in the formula II to obtain flaxseed cyclopeptide A;
The synthesis process of the flaxseed cyclic peptide B comprises the following steps: synthesizing a compound shown in a formula III from 3,4, 5-trioctadecyl phenyl formaldehyde and an amino acid raw material, performing intramolecular amide cyclization reaction on the compound shown in the formula III to obtain a compound shown in a formula IV, and removing 3,4, 5-trioctadecyl benzyl in the compound shown in the formula IV to obtain flaxseed cyclopeptide B;
the intramolecular amide cyclization reaction in this embodiment corresponds to the intramolecular amide cyclization reaction in the third embodiment, namely:
in some embodiments, the reaction system of the amide cyclization reaction is a suspension;
in some embodiments, the amide cyclization reaction is carried out at a reaction temperature of 20 to 30 ℃ for a reaction time of 70 to 74 hours;
In some embodiments, the solvent for the amide cyclization reaction is dichloromethane, methyltetrahydrofuran, or acetonitrile
The manner of removing the 3,4, 5-tris (octadecyloxy) benzyl group in this embodiment is identical to the manner of removing the hydrophobic carrier in the third embodiment, namely:
In some embodiments, the process for removing 3,4, 5-tris (octadecyloxy) benzyl is: and (3) carrying out removal reaction on the compound shown in the formula II or the compound shown in the formula IV under the condition of adding trifluoroacetic acid. More specifically, the temperature of the removal reaction is 20-30 ℃ and the time is 3-5 hours.
Specifically, after removing 3,4, 5-trioctadecyl benzyl, filtering the reacted slurry, concentrating the filtered filtrate, precipitating with methyl tertiary butyl ether, filtering and drying to obtain a crude product. More specifically, the crude product is purified by a reversed-phase high-performance liquid chromatography. Further, the mobile phase A in the reversed-phase high-performance liquid chromatography is trifluoroacetic acid/water solution, and the mobile phase B is trifluoroacetic acid/acetonitrile solution. The concentration of trifluoroacetic acid in the trifluoroacetic acid/water solution is 0.09-0.11%. The concentration of trifluoroacetic acid in the trifluoroacetic acid/acetonitrile solution is 0.09-0.11%.
In order to enable those skilled in the art to more clearly understand the technical scheme of the present invention, the technical scheme of the present invention will be described in detail with reference to specific embodiments.
Example 1:
a synthesis method of flaxseed cyclic peptide A, as shown in figure 1, comprises the following steps:
1. Synthesis of compounds of structure I:
9.11g (10 mmol,1.0 eq) of 3,4, 5-tris (octadecyloxy) phenylformaldehyde, 20mmol (2.0 eq) of acetic acid, 15mmol (1.5 eq) of L-leucine methyl ester and 200ml of dichloromethane are added to a 250ml round bottom flask, stirred until dissolved, 20mmol (2.0 eq) of sodium triacetoxyborohydride is slowly added and the reaction is refluxed for 2 hours, and the reaction is completed by TLC. The mixture was washed three times with 100ml of a saturated aqueous sodium hydrogencarbonate solution and a saturated brine.
The organic phase is concentrated to dryness and added with 200ml of methyltetrahydrofuran, fmoc-L-Ile-OH
15Mmol (1.5 eq), HOBt 15mmol (1.5 eq) and DIC 15mmol (1.5 eq) were reacted at 25℃for 4 hours, and the reaction was complete by TLC. The mixture was washed three times with 100ml of a saturated aqueous sodium hydrogencarbonate solution and a saturated brine. 4.00g (2%) of 4-methylpiperidine was added and the reaction was allowed to proceed at 25℃for 2 hours, followed by completion of the reaction by TLC. The mixture was washed three times with 100ml of a saturated aqueous ammonium chloride solution and a saturated brine. And then sequentially connecting Fmoc-L-Ile-OH, fmoc-L-Leu-OH, fmoc-L-Phe-OH, fmoc-L-Pro-OH and Fmoc-L-Val-OH, wherein the connection method, the use amount and the post-treatment are consistent with those of the connection Fmoc-L-Ile-OH.
60Mmol (6.0 eq) of calcium chloride, 50ml of tetrahydrofuran and 200ml of 1M lithium hydroxide solution were added, and the reaction was completed by TLC under the reaction condition of 0-5℃for 8 hours. Tetrahydrofuran was removed under reduced pressure, and the organic phase was washed three times with 100ml of saturated aqueous ammonium chloride and saturated brine in this order. After concentrating to about 100ml of the reaction system, the mixture was slowly added to 800ml of methanol. The solid was filtered, washed and dried to give 16.33g of an off-white solid, i.e. the compound of structure I, whose mass spectrum is shown in figure 2 in 83.56% yield.
2. Synthesis of flaxseed cyclopeptide a:
In a 250ml round bottom flask were added 15.60g (8.0 mmol,1.0 eq) of the compound of structure I, condensing agent [ EDC-HCl (10.0 eq)/Oxyma (6.0 eq)/sodium bicarbonate (10.0 eq) ] and 600ml of acetonitrile, the reaction system was a suspension, and the reaction was completed by TLC under the reaction condition of 25℃for 72 hours. The solid was filtered, washed and dried to give 15.03g of the compound of structure II as an off-white solid.
The above solid was added to a dichloromethane/trifluoroacetic acid mixed solvent (200 ml, dichloromethane/trifluoroacetic acid=1/1), and reacted at 25 ℃ for 4 hours, and TLC detection of the reaction was complete. The filtrate after filtration was concentrated, precipitated with methyl tert-butyl ether, filtered and dried, and the crude peptide was purified by reverse phase high performance liquid chromatography using a C18 column (50 x 250mm,10 μm), mobile phase a was 0.1% trifluoroacetic acid/aqueous solution, and mobile phase B was 0.1% trifluoroacetic acid/acetonitrile solution. The ultraviolet detection wavelength is 216nm. 7.02g of pure product is obtained after concentration and freeze-drying, the purity is 99.2 percent, and the yield is 67.6 percent. The mass spectrum of the flaxseed cyclopeptide A is shown in figure 3.
Example 2
A synthesis method of flaxseed cyclic peptide B, as shown in figure 4, comprises the following steps:
1. Synthesis of compounds of structure III:
9.11g (10 mmol,1.0 eq) of 3,4, 5-tris (octadecyloxy) phenylformaldehyde, 20mmol (2.0 eq) of acetic acid, 15mmol (1.5 eq) of L-leucine methyl ester and 200ml of dichloromethane are added to a 250ml round bottom flask, stirred until dissolved, 20mmol (2.0 eq) of sodium triacetoxyborohydride is slowly added and the reaction is refluxed for 2 hours, and the reaction is completed by TLC. The mixture was washed three times with 100ml of a saturated aqueous sodium hydrogencarbonate solution and a saturated brine.
The organic phase is concentrated to dryness and added with 200ml of methyltetrahydrofuran, fmoc-L-Met-OH
15Mmol (1.5 eq), HOBt 15mmol (1.5 eq) and DIC 15mmol (1.5 eq) were reacted at 25℃for 4 hours, and the reaction was complete by TLC. The mixture was washed three times with 100ml of a saturated aqueous sodium hydrogencarbonate solution and a saturated brine. 4.00g (2%) of 4-methylpiperidine was added and the reaction was allowed to proceed at 25℃for 2 hours, followed by completion of the reaction by TLC. The mixture was washed three times with 100ml of a saturated aqueous ammonium chloride solution and a saturated brine. And then sequentially connecting Fmoc-L-Ile-OH, fmoc-L-Val-OH, fmoc-L-Phe-OH, fmoc-L-Pro-OH and Fmoc-L-Ile-OH, and connecting the same method, the same amount and the same post-treatment as those of the connection Fmoc-L-Met-OH.
60Mmol (6.0 eq) of calcium chloride, 50ml of tetrahydrofuran and 200ml of 1M lithium hydroxide solution were added, and the reaction was completed by TLC under the reaction condition of 0-5℃for 8 hours. Tetrahydrofuran was removed under reduced pressure, and the organic phase was washed three times with 100ml of saturated aqueous ammonium chloride and saturated brine in this order. After concentrating to about 100ml of the reaction system, the mixture was slowly added to 800ml of methanol. The solid was filtered, washed and dried to give 16.24g of an off-white solid, i.e., the compound of structure III, whose mass spectrum is shown in fig. 5, in 82.36% yield.
2. Synthesis of Linseed cyclopeptide B
In a 250ml round bottom flask were added 15.80g (8.0 mmol,1.0 eq) of the compound of structure III, condensing agent [ EDC-HCl (10.0 eq)/Oxyma (6.0 eq)/sodium bicarbonate (10.0 eq) ] and 400ml of acetonitrile, the reaction system was a suspension, and the reaction was completed by TLC under the reaction condition of 25℃for 72 hours. The solid was filtered, washed and dried to give 15.48g of the compound of structure IV as an off-white solid.
The above solid was added to a dichloromethane/trifluoroacetic acid mixed solvent (200 ml, dichloromethane/trifluoroacetic acid=1/1), and reacted at 25 ℃ for 4 hours, and TLC detection of the reaction was complete. The filtrate after filtration was concentrated, precipitated with methyl tert-butyl ether, filtered and dried, and the crude peptide was purified by reverse phase high performance liquid chromatography using a C18 column (50 x 250mm,10 μm), mobile phase a was 0.1% trifluoroacetic acid/aqueous solution, and mobile phase B was 0.1% trifluoroacetic acid/acetonitrile solution. The ultraviolet detection wavelength is 216nm. After concentration and freeze-drying, 6.86g of pure product is obtained, the purity is 98.7 percent, and the yield is 64.86 percent. The mass spectrum of the flaxseed cyclopeptide B is shown in figure 6.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A polypeptide structural compound with a hydrophobic carrier is characterized in that the chemical structural formula is shown in a formula I,
2.A polypeptide structural compound with a hydrophobic carrier is characterized in that the chemical structure of the polypeptide structural compound is shown in a formula III,
3. Use of a polypeptide structural compound with a hydrophobic carrier according to claim 1 or claim 2 for the preparation of flaxseed cyclic peptides.
4. The method according to claim 3, wherein the polypeptide structure compound with the hydrophobic carrier is subjected to intramolecular amide cyclization reaction to obtain a cyclopeptide compound with the hydrophobic carrier, and the hydrophobic carrier in the cyclopeptide compound with the hydrophobic carrier is removed to obtain the cyclopeptide compound;
Wherein the cyclopeptide compound with the hydrophobic carrier is a compound shown in a formula II or a compound shown in a formula IV,
The cyclic peptide compound is
5. The method according to claim 4, wherein the reaction system of the amide cyclization reaction is a suspension;
Or, the condensing agent for the amide cyclization reaction comprises one or more of EDC-HCl, oxyma and sodium bicarbonate;
Or the reaction temperature of the amide cyclization reaction is 20-30 ℃ and the reaction time is 70-74 hours;
or, the solvent for the amide cyclization reaction is dichloromethane, methyltetrahydrofuran or acetonitrile.
6. The method according to claim 4, wherein the hydrophobic carrier is removed by: removing the cyclic peptide compound with the hydrophobic carrier under the condition of adding trifluoroacetic acid;
Or, after the hydrophobic carrier is removed, filtering the reacted slurry, concentrating the filtered filtrate, precipitating with methyl tertiary butyl ether, filtering and drying to obtain a crude product.
7. A synthesis method of flaxseed cyclic peptide is characterized by comprising a synthesis process of flaxseed cyclic peptide A or/and a synthesis process of flaxseed cyclic peptide B;
The synthesis process of the flaxseed cyclic peptide A comprises the following steps: synthesizing a compound shown in a formula I from 3,4, 5-trioctadecyl phenyl formaldehyde and an amino acid raw material, performing intramolecular amide cyclization reaction on the compound shown in the formula I to obtain a compound shown in a formula II, and removing 3,4, 5-trioctadecyl benzyl in the compound shown in the formula II to obtain flaxseed cyclopeptide A;
The synthesis process of the flaxseed cyclic peptide B comprises the following steps: synthesizing a compound shown in a formula III from 3,4, 5-trioctadecyl phenyl formaldehyde and an amino acid raw material, performing intramolecular amide cyclization reaction on the compound shown in the formula III to obtain a compound shown in a formula IV, and removing 3,4, 5-trioctadecyl benzyl in the compound shown in the formula IV to obtain flaxseed cyclopeptide B;
8. The method for synthesizing flaxseed cyclic peptide according to claim 7, wherein the reaction system of the amide cyclization reaction is a suspension;
Or the reaction temperature of the amide cyclization reaction is 20-30 ℃ and the reaction time is 70-74 hours;
or, the solvent for the amide cyclization reaction is dichloromethane, methyltetrahydrofuran or acetonitrile.
9. The method for synthesizing flaxseed cyclic peptide according to claim 7, wherein the removal of 3,4, 5-tris (octadecyloxy) benzyl group comprises: removing the compound shown in the formula II or the compound shown in the formula IV under the condition of adding trifluoroacetic acid;
Or removing 3,4, 5-trioctadecyl benzyl, filtering the reacted slurry, concentrating the filtered filtrate, precipitating with methyl tertiary butyl ether, filtering and drying to obtain a crude product.
10. The method for synthesizing flaxseed cyclic peptide according to claim 9, wherein the removal reaction is carried out at a temperature of 20 to 30 ℃ for 3 to 5 hours;
Or purifying the crude product by adopting a reversed-phase high-performance liquid chromatography; preferably, the mobile phase A in the reversed-phase high-performance liquid chromatography is trifluoroacetic acid/water solution, and the mobile phase B is trifluoroacetic acid/acetonitrile solution; further preferably, the concentration of trifluoroacetic acid in the trifluoroacetic acid/aqueous solution is 0.09 to 0.11%; further preferably, the concentration of trifluoroacetic acid in the trifluoroacetic acid/acetonitrile solution is 0.09 to 0.11%.
CN202410344725.6A 2024-03-25 2024-03-25 Synthesis method of flaxseed cyclic peptide Pending CN118108794A (en)

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