# US 11,028,094 B2 · Preparative scale conversion of gonyautoxins to neosaxitoxin

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- Number: US 11,028,094 B2
- Document ID: US11028094B2
- Status: Granted
- Kind: B2
- Application number: 17/018,816
- Filed: 2020-09-11
- Published: 2020-12-31
- Granted: 2021-06-08
- Earliest claimed: 2018-09-21
- Applicants: The Cawthron Institute Trust Board
- Inventors: Andrew Ian Selwood; Roelof Van Ginkel; Craig Alan Waugh
- Web page: https://patentgrep.com/patent/US11028094B2

## CPC

- C07D 487/14: Ortho-condensed systems
- C07D 487/20: Spiro-condensed systems
- C12N 1/12: Unicellular algae; Culture media therefor (as new plants A01H13/00)
- C12P 17/18: containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin {(e.g. Rifamycin C12P17/189)}
- C12P 17/182: {Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system (alloxazine or isoalloxazine, e.g. riboflavine C12P25/00)}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}

## Abstract

A method of preparing neosaxitoxin in quantities of a purity sufficient to allow the compound to be used as an active pharmaceutical ingredient (API) is described. The method includes the reductive desulfonation of an unresolved mixture of gonyautoxin 1 (GTX1) and gonyautoxin 4 (GTX4).

## Claims

### Claim 1

A method of preparing a quantity of purified neoSTX comprising:
(a) contacting in solution at a pH in the range 7.2 to 7.8 a quantity of GTX1,4 and a quantity of a dithiol at a temperature and for a time sufficient to provide a conversion product in which greater than 97.5% (w/w) of the quantity of GTX1,4 has been converted to neoSTX; and then
(b) applying the conversion product to a weak cation exchange sorbent and eluting with an aqueous weak acid to separate neoSTX from the dithiol and provide the quantity of purified neoSTX.

### Claim 2 (depends on 1)

The method of claim 1 where the weak cation exchange sorbent is a silica based weak cation exchange sorbent.

### Claim 3 (depends on 2)

The method of claim 2 where the aqueous weak acid is an aqueous organic acid.

### Claim 4 (depends on 3)

The method of claim 3 where the organic acid is acetic acid.

### Claim 5 (depends on 4)

The method of claim 4 where the quantity of GTX1,4 is greater than 100 mg.

### Claim 6 (depends on 5)

The method of claim 5 where the quantity of purified neoSTX has a purity greater than 99.5% (w/w).

### Claim 7 (depends on 6)

The method of claim 6 where the pH of the solution is in the range 7.4 to 7.6.

### Claim 8 (depends on 7)

The method of claim 7 where the dithiol is dithiothreitol.