[go: up one dir, main page]

WO1997010259A1 - Procede d'obtention de peptides muramiques - Google Patents

Procede d'obtention de peptides muramiques Download PDF

Info

Publication number
WO1997010259A1
WO1997010259A1 PCT/RU1996/000254 RU9600254W WO9710259A1 WO 1997010259 A1 WO1997010259 A1 WO 1997010259A1 RU 9600254 W RU9600254 W RU 9600254W WO 9710259 A1 WO9710259 A1 WO 9710259A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
mixture
muramyl peptides
pyridine
target product
Prior art date
Application number
PCT/RU1996/000254
Other languages
English (en)
Russian (ru)
Inventor
Elena Jurievna Bezrukova
Original Assignee
Bezrukov, Mikhail Vasilievich
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 Bezrukov, Mikhail Vasilievich filed Critical Bezrukov, Mikhail Vasilievich
Publication of WO1997010259A1 publication Critical patent/WO1997010259A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
    • C07K9/001—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence having less than 12 amino acids and not being part of a ring structure
    • C07K9/005—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence having less than 12 amino acids and not being part of a ring structure containing within the molecule the substructure with m, n > 0 and m+n > 0, A, B, D, E being heteroatoms; X being a bond or a chain, e.g. muramylpeptides

Definitions

  • 5 of the present compounds may be used by unprotected amino acids, drugs and they are strong in vapors.
  • the resulting product of the active substance is mixed with a mixture of free peptide or amino acid or salt with an acid or an acid that is consumed in or is consumed in
  • the main advantage of the system is the absence of a technical part of the risk of a malfunction of an accident, the result of an accident is a mishap.
  • ⁇ is ⁇ van ⁇ s ⁇ gid ⁇ i ⁇ vaniya ⁇ nechn ⁇ g ⁇ mu ⁇ amil ⁇ e ⁇ ida ⁇ bus- l ⁇ vlena ⁇ a ⁇ v ⁇ zm ⁇ zhn ⁇ s ⁇ yu ⁇ avleniya ⁇ a ⁇ ali ⁇ a ⁇ a ⁇ m ⁇ - nen ⁇ ami is ⁇ dn ⁇ y mixture ⁇ a ⁇ and v ⁇ em ⁇ zhn ⁇ s ⁇ yu gid ⁇ i ⁇ vaniya on ⁇ alladiev ⁇ m ⁇ a ⁇ aliza ⁇ e aldegidn ⁇ y ⁇ my ⁇ -atse ⁇ ilmu-
  • 20 muramyl pheptides do not contain impurities due to the adverse reactions of 0-acylation, mimicking, and transferring.
  • Fig. 4 analytical LNG of the reactive mixture containing the DPP, for separation at 5% of the base of the N-25 in the acetate phase.
  • Pics 1, 2, 3, and 4 residues of the company — 5 garbage consumables and the L-alanyl- ⁇ -glutamine derivative; Acts 5 and 6 are anomalous features of the State Duma.
  • the inventive method for the production of mumamideptides is carried out by the following process.
  • the reactive mixture is vaporized and secreted with mumamideptide using an external compound in the form of a non-reactive compound.
  • muramyl pepids can also be obtained, including those connected with B-isglutamine or ISA ⁇ -isglutamine acid, amyloderin, an essential acid, aminuline, and other
  • the reactive mixture can withstand + 7 ° ⁇ for 17 hours. At the end of the reaction, the solvents are discouraged in a vacuum, add 15 ml of acetic acid, and the product is repaired.
  • the reactive mixture is analyzed (analytical coolant is shown in Fig. 4), dissolves in 15 ml of water, and is applied to a core of 1.5 x 50 cm with a volume that is free of charge. The elution is carried out by water, then 0.04% of the success of acetic acid. The fractions containing the DPP, evaporate and produce 521.8 mg (75%) of the target product, 98% of which is subject to the LJP data (see Fig. 5). EXAMPLE 2.
  • the synthesis of the DPP is as follows: 496, 5 mg (1 mmol) ⁇ -acetylglucosaminyl- ( ⁇ > 1 ⁇ 4) - ⁇ -acetylmutic acid is 2 mg in diameter (2 ml).
  • - Nitrogen 120 ml of ⁇ -methyl methylphenol and leave to stir at 20 ° ⁇ for 17 hours, and then evaporate at 30 ° ⁇ .
  • the resulting reaction mixture at 20 ° C adds 662 mg (2 mmol) of stirring at a temperature of. _.- alanyl- ⁇ -iso-glutamine and 4 ⁇ l-amulide amide 4 mg.
  • the non-active mixture can withstand + 20 ° ⁇ for 40 hours.
  • Example 3 At the end of the reaction, the solvents are removed from the vacuum at 45 ° C.
  • the reactive mixture is dissolved in the water and is partitioned under the conditions of Example 1 on a ring with Diesel-25 in the acetate unit. The elution is carried out by water, then 0.04% of sales of acetic acid. The fractions containing the GDP are disposing of and producing 556.58 mg (80%) of the target product 98% of the total.
  • Example 3 Example 3
  • HDPA The synthesis of HDPA is as follows: 496.5 mg (1 mmol) of ⁇ -acetylglucosaminyl- ( ⁇ 1 - * - 4) - ⁇ -acetylmuric acid, which is diluted with 120 ml of dimethyl Allow to stir at a temperature of 10 C for 17 hours
  • Example 5 The synthesis of ⁇ -acetylglucosaminyl- (£> 1- * 4) - ⁇ -acetylmuru-mil-1-alanyl- ⁇ -glutamic acid has the following effects: 496, 5 mg (1 mg) £ 1- * 4) - ⁇ -acetyl acid is dissolved in 3 ml of D ⁇ , add 256 mg of di (iqueêt-succinimidyl), is consumed, 120 ⁇ l is consumed, it is consumed, it is consumed it has a vapor temperature of 40 ° ⁇ .
  • the resulting reacted mixture at 20 ° C adds 498 mg of stirring solution of L-alanyl-B-glutamic acid and 2 ml-ml-ml ⁇ ea ⁇ tsi ⁇ nnuyu mixture ⁇ s ⁇ avlya- yu ⁇ ⁇ e ⁇ emeshiva ⁇ sya ⁇ i 20 ° C for 19 chas ⁇ v, u ⁇ a ⁇ ivayu ⁇ , za ⁇ em ⁇ e ⁇ eu ⁇ a ⁇ ivayu ⁇ with 20 ml of 50% u ⁇ susn ⁇ y ⁇ isl ⁇ y and ⁇ ma ⁇ g- ⁇ a ⁇ i ⁇ uyu ⁇ ⁇ l ⁇ n ⁇ e to 1, 5 to 50 cm ⁇ ⁇ ⁇ -25 Ze ⁇ a ⁇ e ⁇ at 0, 15 ⁇ u ⁇ susn ⁇ y ⁇ isl ⁇ e .
  • the fractions containing the target product, destroy and receive 518 mg (73%) of the target product 97% of the number.
  • the synthesis of PPPs has the following effects: 496, 50 mg (1 mmol) ⁇ -acetylglucosaminyl- (£ 1 ⁇ 4) - ⁇ -acetylmuic acid dissolves in 3 ml of calcium-dimethylsulfonate, which accounts for up to 256 mg / day. ⁇ -Methylmorphine and leave to stir for 4 hours at 20 ° ⁇ . After evaporation of the resulting reacted mixture, 5,400 mg of ⁇ -alanyl- ⁇ - ⁇ -glutamine, diluted in 6 ml of dilu-malide, is added to 400 mg. The reactive mixture is maintained at + 20 ° C for 17 hours and then evaporates. The resulting preparation was prepared under conditions of Example 1, fractions containing 0 HDPA, and received 556.6 mg (80%) of the target product.
  • HDPA The synthesis of HDPA is as follows: 496, 5 mg (1 mmol) of ⁇ -acetylglucosaminyl- ( ⁇ 1-? 4) - ⁇ -acetylmulic acid is 120 ml. ⁇ -Methylmorphine and leave to stir for 17 hours at +4 ° ⁇ .
  • the claimed invention can be used in medicine and veterinary medicine for the treatment of mumramideptides with a wide range of physiological activity.

Landscapes

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

Abstract

L'invention porte sur un procédé d'obtention de peptides mouramiques physiologiquement actifs, appliqué aux domaines médicaux et vétérinaires. Ce procédé comprend: la production d'éther activé d'acide N-acétylmuramique non protégé ou d'acide N-acétylglucosamine-(β1→4)-N-acétylmuramique; sa condensation avec un acide aminé non protégé, un peptide ou leurs sels, dans de la pyridine ou d'homologues de celle-ci, ou dans leurs mélanges avec des dissolvants organiques; et séparation du produit ciblé par chromatographie. Ce procédé permet à l'utilisateur de produire des peptides muramiques avec un rendement élevé, en ayant recours à des schémas de synthèse qui ne sont constitués que de quelques étapes.
PCT/RU1996/000254 1995-09-11 1996-09-10 Procede d'obtention de peptides muramiques WO1997010259A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU95115861 1995-09-11
RU95115861A RU2083588C1 (ru) 1995-09-11 1995-09-11 Способ получения мурамилпептидов

Publications (1)

Publication Number Publication Date
WO1997010259A1 true WO1997010259A1 (fr) 1997-03-20

Family

ID=20171994

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU1996/000254 WO1997010259A1 (fr) 1995-09-11 1996-09-10 Procede d'obtention de peptides muramiques

Country Status (2)

Country Link
RU (1) RU2083588C1 (fr)
WO (1) WO1997010259A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9085605B2 (en) 2010-05-27 2015-07-21 Shenzhen Salubris Pharmaceuticals Co., Ltd. Chemical synthesis and anti-tumor and anti-metastatic effects of dual functional conjugate

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2181729C1 (ru) * 2000-09-20 2002-04-27 Калюжин Олег Витальевич Производные мурамовой кислоты

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2368282A1 (fr) * 1976-10-22 1978-05-19 Anvar Adjuvant immunologique constitue par le p-amino-phenyl de n-acetyl-muramyl-l-alanyl-d-isoglutamine
SU727647A1 (ru) * 1977-11-02 1980-04-15 Институт биоорганической химии им.М.М.Шемякина Гликопептиды,обладающие противоопухолевой активностью и способ их получени
EP0118364A1 (fr) * 1983-03-04 1984-09-12 Merck & Co. Inc. Dérivés dipeptidyl-D-glucose à activité immunostimulative et leurs méthodes de préparation
US4606857A (en) * 1982-07-27 1986-08-19 Daiichi Seiyaku Co., Ltd. Muramyldipeptide derivatives
SU1558927A1 (ru) * 1988-03-30 1990-04-23 Симферопольский государственный университет им.М.В.Фрунзе Способ получени гидрохлорида @ -6-аминогексилгликозида-N-ацетилмурамоил-L-аланил-Д-изоглутамина

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2368282A1 (fr) * 1976-10-22 1978-05-19 Anvar Adjuvant immunologique constitue par le p-amino-phenyl de n-acetyl-muramyl-l-alanyl-d-isoglutamine
SU727647A1 (ru) * 1977-11-02 1980-04-15 Институт биоорганической химии им.М.М.Шемякина Гликопептиды,обладающие противоопухолевой активностью и способ их получени
US4606857A (en) * 1982-07-27 1986-08-19 Daiichi Seiyaku Co., Ltd. Muramyldipeptide derivatives
EP0118364A1 (fr) * 1983-03-04 1984-09-12 Merck & Co. Inc. Dérivés dipeptidyl-D-glucose à activité immunostimulative et leurs méthodes de préparation
SU1558927A1 (ru) * 1988-03-30 1990-04-23 Симферопольский государственный университет им.М.В.Фрунзе Способ получени гидрохлорида @ -6-аминогексилгликозида-N-ацетилмурамоил-L-аланил-Д-изоглутамина

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9085605B2 (en) 2010-05-27 2015-07-21 Shenzhen Salubris Pharmaceuticals Co., Ltd. Chemical synthesis and anti-tumor and anti-metastatic effects of dual functional conjugate

Also Published As

Publication number Publication date
RU2083588C1 (ru) 1997-07-10

Similar Documents

Publication Publication Date Title
US4330559A (en) Method of treating benign prostatic hypertrophy
US4304726A (en) Process for the preparation of cholesterol derivatives
Suhara et al. Total synthesis of kasugamycin
Kopple et al. Reactivity of Cyclic Peptides. II. cyclo-L-Tyrosyl-L-histidyl and cyclo-L-Tyrosyltriglycyl-L-histidylglycyl
Kurumaya et al. A facile synthesis of δ‐aminolevulinic acid (ALA) regioselectively labeled with 13C and direct observation of enzymatic transformation from ALA to porphobilinogen (PBG)
JPH03176459A (ja) １―（アミノメチル）シクロヘキサン酢酸の製造方法
JPH0791302B2 (ja) エラグ酸の製造法
US4482706A (en) Steroid saponins
WO1997010259A1 (fr) Procede d'obtention de peptides muramiques
England et al. Incorporation of esters into proteins: Improved synthesis of hydroxyacyl tRNAs
Bellosta et al. Synthesis of (2-deoxy-α-d-glyc-2-enopyranosyl) arenes by stereospecific counjugate-addition of organocopper reagents to peracetylated hex-1-enopyran-3-uloses
GB2077284A (en) Process for producing coproporphyrin iii
JP3037991B2 (ja) 新規なアコニチン系化合物および鎮痛・抗炎症剤
EP0178553A2 (fr) Procédé de préparation de L-acides amines substitués aromatiquement
WO1987002366A2 (fr) Nouveaux derives du complexe 13-384 antibiotique oligosaccharide, leur preparation et compositions pharmaceutiques les contenant
Garssen et al. NMR studies of the interaction of gene-V protein of bacteriophage M13 with oligonucleotides
US3714241A (en) PREPARATION OF alpha -METHYL-3,4-DISUBSTITUTED PHENYLALANINES
SONODA et al. A simplified synthesis of 32-oxygenated lanosterol derivatives
Tsui et al. Preparation of 8-methoxycarbonyloctyl glycosides of α-D-mannopyranose, 2-O-α-mannopyranosyl-α-D-mannopyranose, β-D-galactofuranose, and 3-O-β-D-galactofuranosyl-α-D-mannopyranose
CN107663221A (zh) 一种奥贝胆酸的制备方法
EP0342599A2 (fr) Dérivés d'oligosaccharides polyacétyls
Jorgensen et al. Thyroxine analogs. XIX. 3, 5-dimethyl-3'-isopropyl-DL-thyronine
US5770767A (en) Process for producing 2-fluorocyclopropancecarboxlic acid
US6403843B1 (en) Process for the preparation of 1-(3,4-dimethoxyphenyl)ethanol
JPS63270661A (ja) １−〔２−（４−ヒドロキシベンゾイル）エタノイル〕−２−ピペリドン及びその製造法並びにそれを有効成分とするアルコ−ル発酵促進剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA CN JP KR US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA