WO2016145997A1 - Molécule de sucre pharmaceutiquement active et son procédé de synthèse - Google Patents

Molécule de sucre pharmaceutiquement active et son procédé de synthèse Download PDF

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Publication number
WO2016145997A1
WO2016145997A1 PCT/CN2016/075585 CN2016075585W WO2016145997A1 WO 2016145997 A1 WO2016145997 A1 WO 2016145997A1 CN 2016075585 W CN2016075585 W CN 2016075585W WO 2016145997 A1 WO2016145997 A1 WO 2016145997A1
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WO
WIPO (PCT)
Prior art keywords
compound
formula
pharmaceutically active
sugar molecule
group
Prior art date
Application number
PCT/CN2016/075585
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English (en)
Chinese (zh)
Inventor
单宇龙
Original Assignee
淮安市匹克斯生物科技有限公司
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 淮安市匹克斯生物科技有限公司 filed Critical 淮安市匹克斯生物科技有限公司
Priority to ES201790034A priority Critical patent/ES2646628B1/es
Publication of WO2016145997A1 publication Critical patent/WO2016145997A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the invention relates to the technical field of medicinal chemistry, in particular to a medicinal active sugar molecule and a synthetic method thereof.
  • Escherichia coli is a common bacterium that usually occurs in humans and animals. Most strains are harmless, but some of them are harmful to humans. For example, H4 has caused 50 deaths in Germany and France.
  • FebF is the end of E. coli F18 fimbriae. When FebF captures sugar molecules in the intestinal mucosa, it causes diseases such as diarrhea or edema. FebF was found to usually bind to sulfonated acetylgalactosamine and sulfonated lactose, but specific ligands have not been confirmed. To further investigate the structure of the binding site carbohydrates, different sulfonated sugar molecular structures need to be synthesis.
  • the active sugar molecule synthesized by the present invention can be used as an important synthetic intermediate of a sulfonated sugar molecule.
  • the present invention provides a pharmaceutically active sugar molecule having a structure represented by Formula I or II, which can be used to synthesize various sulfonated sugar molecules, thereby being applied to the study of the pathogenic mechanism of Escherichia coli.
  • R 1 and R 2 are each independently selected from a C 1-20 alkylene group substituted by one or more Ra;
  • Each Ra is independently selected from H, alkyl, alkoxy, heterocyclyl, aryl, heteroaryl, halogen or amino, wherein the heterocyclyl and heteroaryl comprise 1-5 independently selected from N , O and S heteroatoms.
  • R1, R2 are, independently of each other, selected from C1-10 alkyl groups substituted by one or more Ra;
  • Each Ra is independently selected from the group consisting of H, C 1-10 alkyl, 3-10 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, F, Cl, Br, I or amino, wherein The heterocyclic group and heteroaryl group contain 1 to 5 hetero atoms independently selected from N, O and S.
  • R1, R2 are independently selected from each other by one or more Ra substituted C1-10 alkylene groups;
  • Each Ra is independently selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, benzene ring, substituted benzene ring, 5-6 membered heterocyclic ring, 5-6 membered heteroaryl, F, Cl, Br, I or NH 2 wherein the heterocyclic group and heteroaryl group contain 1-3 heteroatoms independently selected from N, O and S.
  • R1, R2 are, independently of each other, selected from methylene substituted with one or more Ra;
  • Each Ra is independently selected from the group consisting of H, methyl, ethyl, benzene rings, substituted benzene rings or NH 2 .
  • the compound of formula (I) or (II) according to the invention may be selected from the following compounds:
  • the invention also provides a method for synthesizing the compound represented by the formula (I) or (II), which specifically comprises the following reaction course:
  • R1 and R2 have the above definitions independently of each other;
  • X is a halogen
  • the preparation method of the present invention comprises the following reaction steps:
  • halogen of the halohydrin in the step 2) is F, Cl, Br or I; wherein the alcohol formed is a C 1-10 alkyl alcohol; wherein an acid anhydride is used as a catalyst;
  • the azide in step 3 preferably sodium azide or potassium azide
  • R1 and R2 have the above definition independently of each other; and X is a halogen.
  • halogen refers to fluoro, chloro, bromo and iodo.
  • C 1-20 alkyl is understood to preferably denote a straight or branched saturated monovalent hydrocarbon radical having from 1 to 20 carbon atoms, preferably a C 1-10 alkyl group.
  • C1-6 alkyl is understood to preferably denote a straight or branched saturated monovalent hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms, such as methyl, ethyl, propyl, butyl.
  • the group has 1, 2, 3 or 4 carbon atoms ("C1-4 alkyl”), such as methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec. Butyl, tert-butyl, more particularly, the group has 1, 2 or 3 carbon atoms ("C1-3 alkyl”), such as methyl, ethyl, n-propyl or isopropyl.
  • C1-4 alkyl such as methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec. Butyl, tert-butyl, more particularly, the group has 1, 2 or 3 carbon atoms (“C1-3 alkyl”), such as methyl, ethyl, n-propyl or isopropyl.
  • alkylene refers to any divalent straight or branched hydrocarbon group
  • C 1-20 alkylene is understood to preferably denote a straight or branched saturated divalent having from 1 to 20 carbon atoms.
  • a hydrocarbyl group preferably a C 1-10 alkyl group, is understood to preferably denote a straight or branched saturated divalent hydrocarbon radical having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms
  • the alkylene group including -(CH 2 ) 1-10 -, particularly -CH 2 -, -(CH 2 ) 2 -, -(CH 2 ) 3 -, -(CH 2 ) 4 -, -( CH 2 ) 5 -, -(CH 2 ) 6 - or -CH(CH 3 )-, -C(CH 3 ) 2 -, -CH(C 6 H 5 )-, -CH(CH 2 CH 3 )- Wait.
  • heterocyclyl means a saturated monovalent monocyclic or bicyclic hydrocarbon ring containing from 1 to 5 heteroatoms independently selected from N, O and S, preferably “3-10 membered heterocyclyl".
  • heterocyclyl means a saturated monovalent monocyclic or bicyclic hydrocarbon ring containing from 1 to 5, preferably from 1 to 3, heteroatoms selected from N, O and S.
  • C6-10 aryl is understood to preferably denote a monovalent aromatic or partially aromatic ring having 6 to 10 carbon atoms. It is understood to preferably denote a monovalent aromatic or partially aromatic ring having 6, 7, 8, 9, 10 carbon atoms.
  • 5-10 membered heteroaryl is understood to include a monovalent monocyclic, bicyclic or tricyclic aromatic ring system having from 5 to 10 ring atoms and containing from 1 to 5 independently selected from N, O. And the hetero atom of S.
  • the sugar molecule of the present invention can be used as an important intermediate for synthesizing sulfonated sugar molecules for studying the pathogenic mechanism of Escherichia coli;
  • the compound provided in the present invention has an azide group as a linking group, and can be better linked to other molecular structures, and can be used for studying the molecular structure of Escherichia coli, and has important significance in drug research and development;
  • the synthetic method provided by the present invention can be used to prepare different pharmaceutically active sugar molecules, and the operation is simple and convenient.
  • VO(OTf) 2 (0.05 eq, 40 mg) was added to a round bottom flask, and dry acetonitrile (1.77 mL) and dimethoxypropane (10 eq., 2.9 mL) were added and stirred for 10 minutes to dissolve thoroughly. The color turned brown; then the mixture 5 (50 mg, 118 mmol) was added and the reaction was carried out at room temperature for two days; the progress of the reaction was monitored by TLC (EtOAc/MeOH, 4:1). The title product 001 (36 mg, 69%) was obtained.
  • the invention adopts azide group as a linking group, can be better connected with other molecular structures, and is used for synthesizing sulfonated sugar molecules, thereby being applied to research on the pathogenic mechanism of Escherichia coli and applied to the field of medical technology research. And the method can be used for synthesizing a plurality of compounds, and the operation is simple.

Abstract

La présente invention concerne une molécule de sucre pharmaceutiquement active et son procédé de synthèse. La molécule de sucre présente une structure telle que présentée par la formule (I) ou (II) et peut être utilisée pour la synthèse d'une molécule de sucre sulfonée, de sorte qu'elle peut être en outre appliquée à la recherche sur la pathogenèse d'E. coli. Le procédé de synthèse décrit par la présente invention est simple, pratique et facile à utiliser, et peut être utilisé pour la synthèse d'une diversité de molécules de sucre.
PCT/CN2016/075585 2015-03-13 2016-03-04 Molécule de sucre pharmaceutiquement active et son procédé de synthèse WO2016145997A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
ES201790034A ES2646628B1 (es) 2015-03-13 2016-03-04 Molécula de azúcar activa farmacéuticamente y su método de síntesis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201510109400.0A CN104788512A (zh) 2015-03-13 2015-03-13 一种药物活性糖分子合成在抵抗大肠杆菌中的应用方法
CN201510109400.0 2015-03-13

Publications (1)

Publication Number Publication Date
WO2016145997A1 true WO2016145997A1 (fr) 2016-09-22

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PCT/CN2016/075585 WO2016145997A1 (fr) 2015-03-13 2016-03-04 Molécule de sucre pharmaceutiquement active et son procédé de synthèse

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CN (1) CN104788512A (fr)
ES (1) ES2646628B1 (fr)
WO (1) WO2016145997A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112480188A (zh) * 2020-11-04 2021-03-12 天津科技大学 唾液酸乳糖糖苷和/或类似物、合成方法及应用

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104788512A (zh) * 2015-03-13 2015-07-22 淮安市匹克斯生物科技有限公司 一种药物活性糖分子合成在抵抗大肠杆菌中的应用方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104788512A (zh) * 2015-03-13 2015-07-22 淮安市匹克斯生物科技有限公司 一种药物活性糖分子合成在抵抗大肠杆菌中的应用方法

Patent Citations (1)

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CN104788512A (zh) * 2015-03-13 2015-07-22 淮安市匹克斯生物科技有限公司 一种药物活性糖分子合成在抵抗大肠杆菌中的应用方法

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PORNSURIYASAK, P. ET AL.: "Synthesis of Cancer-Associated Glycoantigens: Stage-Specific Embryonic Antigen 3 (SSEA-3", CARBOHYDRATE RESEARCH, vol. 341, no. 10, 27 April 2006 (2006-04-27), pages 1458 - 1466, XP025010324 *
SUN, BIN ET AL.: "an Efficient Approach for Total Synthesis of Aminopropyl Functionalized Ganglioside GM1b", TETRAHEDRON LETTERS, vol. 53, no. 42, 23 August 2012 (2012-08-23), pages 5711 - 5715, XP028938138 *
SUN, BIN ET AL.: "Total Synthesis of the Aminopropyl Functionalized Ganglioside GM1", SCIENCE CHINA : CHEMISTRY, vol. 55, no. 1, 31 December 2012 (2012-12-31), pages 31 - 35, XP055312132 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112480188A (zh) * 2020-11-04 2021-03-12 天津科技大学 唾液酸乳糖糖苷和/或类似物、合成方法及应用

Also Published As

Publication number Publication date
ES2646628B1 (es) 2018-10-05
ES2646628A2 (es) 2017-12-14
ES2646628R1 (es) 2017-12-27
CN104788512A (zh) 2015-07-22

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