CL2020003015A1 - Preparative-scale conversion of goniautoxins into neosaxitoxin - Google Patents

Preparative-scale conversion of goniautoxins into neosaxitoxin

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Publication number
CL2020003015A1
CL2020003015A1 CL2020003015A CL2020003015A CL2020003015A1 CL 2020003015 A1 CL2020003015 A1 CL 2020003015A1 CL 2020003015 A CL2020003015 A CL 2020003015A CL 2020003015 A CL2020003015 A CL 2020003015A CL 2020003015 A1 CL2020003015 A1 CL 2020003015A1
Authority
CL
Chile
Prior art keywords
neosaxitoxin
goniautoxins
preparative
scale conversion
goniautoxin
Prior art date
Application number
CL2020003015A
Other languages
Spanish (es)
Inventor
Andrew Ian Selwood
Ginkel Roelof Van
Craig Alan Waugh
Original Assignee
The Cawthron Inst Trust Board
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 The Cawthron Inst Trust Board filed Critical The Cawthron Inst Trust Board
Publication of CL2020003015A1 publication Critical patent/CL2020003015A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/16—Peri-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/12—Unicellular algae; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/12—Unicellular algae; Culture media therefor
    • C12N1/125—Unicellular algae isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/182—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00—Bioreactors or fermenters specially adapted for specific uses
    • C12M21/02—Photobioreactors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/14—Bags
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/22—Transparent or translucent parts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/26—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pH
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/02—Separating microorganisms from the culture medium; Concentration of biomass
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/89—Algae ; Processes using algae

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Biomedical Technology (AREA)
  • Botany (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Saccharide Compounds (AREA)

Abstract

Se describe un método para preparar neosaxitoxina en cantidades de una pureza suficiente para permitir que el compuesto se use como ingrediente farmacéutico activo (API). El método incluye la desulfonación reductora de una mezcla no resuelta de goniautoxina 1 (GTX1) y goniautoxina 4 (GTX4), mediante el uso de un ditiol (como DTT o DTBA) en una solución donde el pH está en el rango de 7,4 a 7,6. El producto de reacción se purifica usando un sorbente de intercambio catiónico débil a base de sílice para separar la neosaxitoxina del ditiol.A method is described for preparing neosaxitoxin in amounts of sufficient purity to allow the compound to be used as an active pharmaceutical ingredient (API). The method includes the reductive desulfonation of an unresolved mixture of goniautoxin 1 (GTX1) and goniautoxin 4 (GTX4), by using a dithiol (such as DTT or DTBA) in a solution where the pH is in the range of 7.4 to 7.6. The reaction product is purified using a silica-based weak cation exchange sorbent to separate neosaxitoxin from dithiol.

CL2020003015A 2018-09-21 2020-11-19 Preparative-scale conversion of goniautoxins into neosaxitoxin CL2020003015A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2018/057274 WO2020058750A1 (en) 2018-09-21 2018-09-21 A semisynthetic method of preparing neosaxitoxin

Publications (1)

Publication Number Publication Date
CL2020003015A1 true CL2020003015A1 (en) 2021-06-25

Family

ID=69888393

Family Applications (1)

Application Number Title Priority Date Filing Date
CL2020003015A CL2020003015A1 (en) 2018-09-21 2020-11-19 Preparative-scale conversion of goniautoxins into neosaxitoxin

Country Status (8)

Country Link
US (2) US10822344B2 (en)
JP (1) JP7110403B2 (en)
CN (1) CN113166164B (en)
CA (1) CA3113727A1 (en)
CL (1) CL2020003015A1 (en)
GB (1) GB2587997B (en)
SG (1) SG11202102830SA (en)
WO (2) WO2020058750A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12018034B2 (en) 2018-09-21 2024-06-25 The Cawthron Institute Trust Board Semisynthetic methods of preparing GTX1,4 and neosaxitoxin
WO2020058750A1 (en) * 2018-09-21 2020-03-26 The Cawthron Institute Trust Board A semisynthetic method of preparing neosaxitoxin
CN112461913B (en) * 2020-11-06 2022-02-22 华南农业大学 Method for improving identification capability of isomer compound
FR3130842B1 (en) 2021-12-22 2025-06-27 CarbonWorks PROCESS FOR CAPTURING PHYTOTOXINS IN A BIOLOGICAL REACTOR

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003012699A (en) * 2001-07-04 2003-01-15 Japan Science & Technology Corp Production method of anti-narcotic shellfish toxin antibody, novel antibody, ELISA measurement kit using the antibody, system-labeled venom sample by the production method
JP2006098293A (en) * 2004-09-30 2006-04-13 Japan Science & Technology Agency How to convert paralytic shellfish poison components
US8952152B2 (en) * 2009-03-24 2015-02-10 Proteus S.A. Methods for purifying phycotoxins, pharmaceutical compositions containing purified phycotoxins, and methods of use thereof
CL2009000723A1 (en) 2009-03-24 2009-06-19 Proteus Sa Industrial purification method of biologically active phycotoxins comprising providing an adequate amount of a source of phycotoxins such as the cultivation of a cyanobacterial clone.
JP6422814B2 (en) * 2015-04-16 2018-11-14 学校法人北里研究所 Method for producing decarbamoyl saxitoxin and its analogs
WO2020058750A1 (en) * 2018-09-21 2020-03-26 The Cawthron Institute Trust Board A semisynthetic method of preparing neosaxitoxin

Also Published As

Publication number Publication date
CA3113727A1 (en) 2020-03-26
SG11202102830SA (en) 2021-04-29
US10822344B2 (en) 2020-11-03
US20200407367A1 (en) 2020-12-31
CN113166164B (en) 2024-01-30
JP2021526539A (en) 2021-10-07
JP7110403B2 (en) 2022-08-01
US11028094B2 (en) 2021-06-08
CN113166164A (en) 2021-07-23
WO2020058750A1 (en) 2020-03-26
GB202018189D0 (en) 2021-01-06
GB2587997B (en) 2023-05-10
WO2020058949A1 (en) 2020-03-26
NZ770197A (en) 2024-04-26
US20200255441A1 (en) 2020-08-13
GB2587997A (en) 2021-04-14

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