WO2019127919A1 - Composé porteur pour la synthèse en phase liquide de polypeptide, son procédé de préparation et son utilisation - Google Patents

Composé porteur pour la synthèse en phase liquide de polypeptide, son procédé de préparation et son utilisation Download PDF

Info

Publication number
WO2019127919A1
WO2019127919A1 PCT/CN2018/079276 CN2018079276W WO2019127919A1 WO 2019127919 A1 WO2019127919 A1 WO 2019127919A1 CN 2018079276 W CN2018079276 W CN 2018079276W WO 2019127919 A1 WO2019127919 A1 WO 2019127919A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
fmoc
reaction
fused ring
carrier
Prior art date
Application number
PCT/CN2018/079276
Other languages
English (en)
Chinese (zh)
Inventor
叶思雷
陈新亮
宓鹏程
陶安进
袁建成
Original Assignee
深圳翰宇药业股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 深圳翰宇药业股份有限公司 filed Critical 深圳翰宇药业股份有限公司
Publication of WO2019127919A1 publication Critical patent/WO2019127919A1/fr

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/20—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms
    • C07C1/207—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms from carbonyl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C13/00—Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
    • C07C13/28—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
    • C07C13/32—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings
    • C07C13/62—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with more than three condensed rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
    • C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
    • C07C217/58—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C23/00—Compounds containing at least one halogen atom bound to a ring other than a six-membered aromatic ring
    • C07C23/18—Polycyclic halogenated hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
    • C07C25/18—Polycyclic aromatic halogenated hydrocarbons
    • C07C25/22—Polycyclic aromatic halogenated hydrocarbons with condensed rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/235—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring and to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C43/253—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring and to a carbon atom of a ring other than a six-membered aromatic ring containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
    • 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
    • C07K7/16—Oxytocins; Vasopressins; Related peptides
    • 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

Definitions

  • the invention relates to the field of polypeptide synthesis, in particular to a compound for liquid phase synthesis of a polypeptide, a preparation method thereof and use thereof.
  • the method of solid phase synthesis can avoid the cumbersome separation and purification steps, and has obvious advantages compared with the liquid phase method: (1) during the synthesis of the polypeptide, the peptide chain is attached to the insoluble carrier, so the product peptide is also insoluble. Easy to wash and easy to filter; (2) excess reaction can be added to the reaction to complete the reaction, while excess reagents and by-products can be removed by washing and filtration; (3) the whole reaction is carried out in the same container, avoiding the liquid The mechanical loss caused by multiple precipitation, washing and separation in phase synthesis is simple and quick to operate; (4) The operation has strong repeatability and is beneficial to the automation of peptide synthesis reaction. At present, peptide synthesis is mostly carried out by solid phase synthesis.
  • solid phase synthesis requires the use of a solid phase carrier resin.
  • the main solid phase carrier resins are: polystyrene-divinylbenzene crosslinked resin; polyamide resin; polyethylene monoethylene glycol resin.
  • the solid phase synthesis of peptides cannot effectively separate the intermediate reaction steps and effectively separate the impurities generated in the process, resulting in complex impurity components in the final product, which is difficult to separate and purify. Due to the use of solid phase carrier, the synthesis scale is replaced by resin.
  • the degree of synthesis such as the degree of resin, resin particle size, mechanical properties, etc., is generally significantly smaller than the liquid phase method.
  • Commonly used solid phase synthetic resins are usually coupled with a linker to facilitate the coupling of amino acids. Among them, common linker-resins include wang resin, amino resin and trityl chloride resin.
  • liquid phase synthetic carriers have been reported in the prior art, such as HO-TAGa, HO-TAGb, NH2-DPM, and Br-T.
  • the present application discloses a fused ring compound which can be used as a liquid carrier for a polypeptide having the following formula A or B:
  • X is selected from the group consisting of H, F, Cl, Br, I or a group having a hydroxyl group, an amino group, a carboxyl group, or a halogen;
  • Y is selected from H, F, Cl, Br or I.
  • the X is selected from the group consisting of H, F, Cl, Br, I,
  • Another aspect of the present invention provides a liquid phase synthetic carrier having the structural formula described above in Formula A.
  • Another aspect of the present invention provides a method of preparing a liquid phase synthetic carrier according to the present invention, which comprises the steps of:
  • step 1) is:
  • step 2) is
  • a functional functional group is further coupled to give a functionalized fused ring compound.
  • step 2-1) is or The mixture was heated under reflux in NBS (N-bromosuccinimide) or N-chlorosuccinimide and BPO (benzoyl peroxide) and an organic solvent until the reaction was completed and methanol was recrystallized.
  • NBS N-bromosuccinimide
  • BPO benzoyl peroxide
  • step 2-2) is taken or Reacted with p-hydroxymethylphenol under potassium carbonate or or
  • substitution reaction is carried out under potassium carbonate conditions, and after completion of the reaction, hydrogenation is carried out in sodium borohydride and ethanol until the reaction is completed, and methanesulfonic acid and Fmoc-NH 2 are added to complete the reaction under sodium carbonate to remove the Fmoc protecting group. get or
  • Another aspect of the invention provides the use of a compound of formula A or B as a liquid phase synthetic carrier.
  • a method for synthesizing a polypeptide wherein a compound represented by Formula A or B is used as a liquid phase synthesis carrier, and an amino acid is sequentially coupled to a functional group of a compound represented by Formula A or B.
  • the amino acid is coupled by activating a carboxyl component with a condensing agent, and condensing with an amino component under basic conditions, removing an amino protecting group, and continuing to couple the next amino acid.
  • the peptide is cleaved to synthesize the carrier until the polypeptide is completed.
  • the condensing agent is selected from one or more of EDCI, EDC, DCC, DIC, HATU, HBTU, HOAt, HOBt, PyAOP, PyBOP.
  • the basic condition is provided by one or more of DIEA, NMM, TEA, pyridine, DBU, N-methylmorpholine, trimethylpyridine or lutidine.
  • the amino protecting group is removed under basic conditions, and the amino protecting group is preferably removed with diethylamine and DBU.
  • the amino protecting group is selected from the group consisting of Fmoc or Boc.
  • TFA TIS: H 2 O composition
  • TFA: TIS: H 2 O 95: 2.5: 2.5.
  • the compound represented by Formula A or B has one or more functional groups in an amino group, a carboxyl group, a hydroxyl group, and a halogen.
  • a method for synthesizing terlipressin which comprises a compound represented by formula A or B as a liquid phase synthesis carrier, coupling Fmoc-Gly 1 -OH, removing an amino protecting group, and thereby The method sequentially couples Fmoc-Lys(Boc)-OH, Fmoc-Cys(Trt)-OH, Fmoc-Pro-OH, Fmoc-Asn(Trt)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Phe- OH, Fmoc-Tyr(tBu)-OH, Fmoc-Cys(Trt)OH, Fmoc-Gly-Gly-OH and Boc-Gly-OH.
  • the liquid phase is synthesized into a carrier and purified to obtain a Teliga. Pressure hormone.
  • substitution reaction is carried out under potassium carbonate conditions, and after completion of the reaction, hydrogenation is carried out in sodium borohydride and ethanol until the reaction is completed, and methanesulfonic acid and Fmoc-NH 2 are added to complete the reaction under sodium carbonate to remove the Fmoc protecting group.
  • the preparation method of the liquid carrier with the compound A as the parent compound in the present invention is as follows:
  • the liquid carrier is used for peptide synthesis, and the operation is simpler than conventional liquid phase synthesis;
  • the liquid carrier is used for peptide synthesis, and the synthesis scale is larger than the traditional solid phase synthesis;
  • the carrier utilization rate is high, and the molecular weight of the liquid carrier reported in Org. Lett. 17 (2015) 4264-4267) and Tetrahedron 67 (2011) 6633-6643 is 832, and only one peptide chain can be synthesized;
  • the obtained amino-phase carrier has a molecular weight of 2758, and 9 peptide chains can be synthesized, and the average molecular weight of one peptide chain is 306.
  • Figure 1 is a H-NMR (400 M Hz) spectrum of compound d.
  • Figure 3 is a mass spectrum of compound d.
  • Figure 4 is a mass spectrum of the carrier compound e.
  • Figure 5 is a mass spectrum of the carrier compound 3.
  • Figure 6 is a mass spectrum of the carrier compound 4.
  • Figure 7 is a linear peptide mass spectrum of terlipressin.
  • Figure 8 is a mass spectrum of terlipressin.
  • Figure 9 is an HPLC chromatogram of terlipressin.
  • Figure 11 is an amino-type liquid carrier compound having the compound A as a precursor.
  • Figure 12 is an amino-type liquid carrier compound in which Compound B is the parent.
  • Extract with CH 2 Cl 2 (3 ⁇ 1500 mL) combine the organic phases, add two times (2 ⁇ 500 ml) with 0.05 mol/L H 2 SO 4 solution, wash twice with saturated NaHCO 3 solution (2 ⁇ 500 ml), and saturate.
  • the NaCl solution was washed once (1 ⁇ 500 ml) and finally dried over anhydrous Na 2 SO 4 .
  • the organic phase was concentrated and crystallized from ethyl acetate to afford 100.2 g of Compound C as a white solid.
  • the obtained filtrate was partitioned and the organic phase was collected.
  • the organic phase was concentrated to dryness at 45 ° C.
  • the filter cake was combined with the concentrated residue and then beaten twice with a mixture of methanol and acetonitrile (1:1, 200 mL). After filtration, the cake was vacuum dried at 45 ° C for 5 hours to give a white solid compound of 25.2 g, yield 98%.
  • the compound 7 86.5 g (18.4 mmol) was weighed into a 1 L three-necked flask, and toluene (300 mL) and ethanol (400 mL) were added to the reaction flask, stirred well, and then sodium hydroxide (7.5 g, 181 mmol) was added.
  • the reaction solution was warmed to 110 ° C and stirring was continued for 16 hours.
  • Water (500 mL) and n-hexane (240 mL) ethyl acetate (300 mL) were successively added to the reaction mixture, and the mixture was stirred for 15 minutes, and then filtered. The filter cake was washed twice with purified water (200 mL ⁇ 2).
  • the obtained filtrate was partitioned and the organic phase was collected.
  • the organic phase was concentrated to dryness at 45 ° C.
  • the filter cake was combined with the concentrated residue and beaten twice with a mixture of methanol and acetonitrile (1:1, 300 mL). After filtration, the cake was dried under vacuum at 45 ° C for 5 hours to give a white solid.
  • the amino-type liquid carrier obtained in Example 1 was used for the specific peptide sequence NH 2 -Gly 12 -Gly 11 -Gly 10 -Cys 9 -Tyr 8 -Ph 7 e-Gln 6 -Asn 5 -Pro 4 -Cys 3 Synthesis of -Lys 2 -Gly 1 -NH 2 (Teripressin Peptide). 1. Coupling the first amino acid (Fmoc-Gly 1 -OH)
  • the reaction mixture was concentrated to a viscous material under reduced pressure at 30 ° C, and methanol (60 mL) was added to the viscous material and stirred for 2 hours. Filter and filter cake was washed three times with methanol (20 mL x 3). The filter cake was vacuum dried at 40 ° C for 5 hours to obtain a compound m 45.6 g (yield: 96%).
  • the reaction mixture was concentrated under reduced pressure at 30 ° C to a viscous material, and acetonitrile (20 mL) was added to the viscous material and stirred for 30 minutes. Filter and filter cake twice with methanol (10 mL x 2). The filter cake was vacuum dried at 40 ° C for 2 hours to give an off-white solid (27.6 g).
  • reaction mixture was concentrated under reduced pressure to a viscous material at 30 ° C, and methanol (20 mL) was added to the viscous material and stirred for 2 hours. Filter and filter cake was washed three times with methanol (10 mL x 3). The filter cake was vacuum dried at 40 ° C for 3 hours to give compound n.
  • terlipressin linear crude peptide 75.1 g was dissolved in a 75 L buffer system with a buffer system of 200 mmol/L sodium dihydrogen phosphate, 25 mmol/L guanidine hydrochloride and 75 mmol/L ammonium acetate in 20% DMSO.
  • the pH was 7.8, the exposure was placed at room temperature, and the mixture was oxidized for more than 10 hours.
  • the linear peptide reaction was completely glacialized with acetic acid to adjust the pH to 3 to 5 to obtain a terpene sulphate crude peptide solution.
  • the obtained crude peptide solution was prepared by NOVASEP RP-HPLC system with a wavelength of 220 nm, a reversed-phase C18 column, purified by a conventional 0.1% TFA/water, acetonitrile mobile phase system, desalted, and the peak fraction was collected, concentrated by rotary evaporation, and lyophilized. 51.3 g of terlipressin peptide was obtained, the HPLC purity was greater than 99.5%, and the maximum single impurity was less than 0.1% of the total yield of 53.8%. [M+H + ]: 1227.753.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un composé porteur pour la synthèse en phase liquide d'un polypeptide, son procédé de préparation et son utilisation, et concerne plus particulièrement un composé cyclique fusionné qui peut être utilisé comme porteur en phase liquide du polypeptide. Le composé cyclique fusionné est représenté par la formule (A) ou (B), dans laquelle X est choisi parmi H, F, Cl, Br, I ou un groupe portant hydroxy, amino, carboxy, ou halogène, et Y est choisi parmi H, F, Cl, Br ou I. Le composé porteur pour la synthèse en phase liquide selon la présente invention est simple à préparer et présente une efficacité de réaction élevée.
PCT/CN2018/079276 2017-12-29 2018-03-16 Composé porteur pour la synthèse en phase liquide de polypeptide, son procédé de préparation et son utilisation WO2019127919A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201711479683.3A CN109988056B (zh) 2017-12-29 2017-12-29 一种用于多肽液相合成载体的化合物及其制备方法和用途
CN201711479683.3 2017-12-29

Publications (1)

Publication Number Publication Date
WO2019127919A1 true WO2019127919A1 (fr) 2019-07-04

Family

ID=67062949

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/079276 WO2019127919A1 (fr) 2017-12-29 2018-03-16 Composé porteur pour la synthèse en phase liquide de polypeptide, son procédé de préparation et son utilisation

Country Status (2)

Country Link
CN (1) CN109988056B (fr)
WO (1) WO2019127919A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115368221A (zh) * 2022-08-02 2022-11-22 成都圣诺生物科技股份有限公司 小分子载体及其制备方法和其在多肽合成中的应用

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111205175A (zh) * 2020-03-17 2020-05-29 京博农化科技有限公司 一种提高5-氯-1-茚酮收率的合成方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101693738A (zh) * 2009-10-29 2010-04-14 深圳市翰宇药业有限公司 一种固相氧化环合合成特利加压素的方法
CN105367627A (zh) * 2014-08-29 2016-03-02 安徽工程大学 一种特利加压素的制备方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016140232A1 (fr) * 2015-03-04 2016-09-09 Jitsubo株式会社 Procédé de synthèse peptidique
CN105418736A (zh) * 2015-12-30 2016-03-23 济南康和医药科技有限公司 一种固液结合制备特利加压素的方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101693738A (zh) * 2009-10-29 2010-04-14 深圳市翰宇药业有限公司 一种固相氧化环合合成特利加压素的方法
CN105367627A (zh) * 2014-08-29 2016-03-02 安徽工程大学 一种特利加压素的制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HAN, XIANG ET AL.: "Application of Solid-Phase Peptides Synthesis", PROGRESS IN PHARMACEUTICAL SCIENCES - OVERVIEW AND MONOGRAPH, vol. 28, no. 1, 31 December 2004 (2004-12-31), pages 10 - 14 *
LI, YONGZHEN ET AL.: "Progress in Synthesis and Applications of Polypeptides", CHEMISTRY & BIOENGINEERING, vol. 27, no. 4, 31 December 2010 (2010-12-31), pages 9 - 14 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115368221A (zh) * 2022-08-02 2022-11-22 成都圣诺生物科技股份有限公司 小分子载体及其制备方法和其在多肽合成中的应用
CN115368221B (zh) * 2022-08-02 2023-05-23 成都圣诺生物科技股份有限公司 小分子载体及其制备方法和其在多肽合成中的应用

Also Published As

Publication number Publication date
CN109988056B (zh) 2020-08-07
CN109988056A (zh) 2019-07-09

Similar Documents

Publication Publication Date Title
WO2017114238A1 (fr) Procédé de synthèse de l'ételcalcétide
Chung et al. Cyclic peptide facial amphiphile preprogrammed to self-assemble into bioactive peptide capsules
JP2017521487A (ja) ガニレリクス前駆体、及びそれを用いた酢酸ガニレリクスの製造方法
CN112386707B (zh) 一种肿瘤靶向多肽药物偶联物及其制备方法
WO2019184089A1 (fr) Composé, son procédé de préparation et son utilisation
WO2018205401A1 (fr) Procédé de préparation de plecanatide
WO2019127919A1 (fr) Composé porteur pour la synthèse en phase liquide de polypeptide, son procédé de préparation et son utilisation
WO2020199461A1 (fr) Procédé de synthèse d'un composé dérivé de polypeptide
CN107056894B (zh) 一种片段法固相合成醋酸加尼瑞克的方法
WO2019127921A1 (fr) Composé pour support de synthèse polypeptidique en phase liquide, son procédé de préparation et son utilisation
CN112585153B (zh) 一种化合物或其盐及其制备方法与应用
CN110642936B (zh) 一种制备特立帕肽的方法
WO2019127920A1 (fr) Support sphérique en phase liquide, son procédé de préparation et son utilisation
CN114478708B (zh) 一种加尼瑞克的片段固相合成方法
CN108484735B (zh) 一类广泛活性环七肽Reniochalistatin A-D的合成方法
WO2021103458A1 (fr) Procédé de synthèse en phase solide de dégarélix
EP3894426B1 (fr) Voies de phase de solution pour hexapeptides wnt
CN110386964B (zh) 一种亮丙瑞林的固液合成方法
WO2021026800A1 (fr) Procédé de synthèse d'acétate de dégarélix
CN108690121B (zh) 一种奈米非肽液相制备方法
CN113801190A (zh) 寡肽-1盐酸盐的制备方法
WO2018205402A1 (fr) Procédé de synthèse de l'ularitide
EP3233899B1 (fr) Procédé de préparation de pasiréotide
CN116573992B (zh) 一种非经典固相合成载体及其制备方法与应用
RU2799031C2 (ru) Линейные жидкофазные пути для гексапептидов wnt

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18896495

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18896495

Country of ref document: EP

Kind code of ref document: A1