# US 10,307,390 B2 · Method of synthesising sulforaphane > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,307,390 B2 - Document ID: US10307390B2 - Status: Granted - Kind: B2 - Application number: 15/392,370 - Filed: 2016-12-28 - Published: 2017-04-27 - Granted: 2019-06-04 - Earliest claimed: 2012-06-01 - Assignees: PharmAgra Labs, Inc. - Applicants: PharmAgra Labs, Inc. - Inventors: Sahadeva Reddy Damireddi; Kpakpo Ambroise Akue; Jared K Nelson; Albert Roger Frisbee; Peter Wyatt Newsome - Web page: https://patentgrep.com/patent/US10307390B2 ## CPC - A61K 31/26: Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters - A61K 31/724: Cyclodextrins - A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)} - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 35/00: Antineoplastic agents - B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery - C07C 315/02: by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides - C07C 331/20: of a saturated carbon skeleton - C08B 37/0015: {Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes} - C08L 5/16: Cyclodextrin; Derivatives thereof - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21) - C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06) ## Abstract The present invention relates to a method of synthesizing sulforaphane by reacting a compound of formula (A) with an oxidizing agent in an aqueous solvent and in the presence of a catalyst. The invention further provides a method of synthesizing a stabilized complex of sulforaphane and cyclodextrin by mixing the sulforaphane prepared by the methodology defined herein with cyclodextrin in an aqueous solvent. ## Claims ### Claim 1 A process for the preparation of a complex of sulforaphane and cyclodextrin, the process comprising: (i) reacting, in an aqueous solvent, a compound of formula A: with an oxidizing agent and in the presence of a catalyst to form sulforaphane; and (ii) mixing the sulforaphane from step (i) with cyclodextrin in an aqueous solvent to form a precipitate of the sulforaphane-cyclodextrin complex, wherein in step (i) 1 to 2 molar equivalents of oxidizing agent, relative to the compound of formula A, is used. ### Claim 2 (depends on 1) A process according to claim 1, wherein the solvent in step (i) and step (ii) is water. ### Claim 3 (depends on 1, 2) A process according to claim 1 or claim 2, wherein the oxidizing agent is hydrogen peroxide or a water soluble or miscible organic per-acid, or a mixture thereof. ### Claim 4 (depends on 3) A process according to claim 3, wherein the oxidizing agent is hydrogen peroxide. ### Claim 5 (depends on 1) A process according to claim 1, wherein the catalyst is selected from cyclodextrin and organic or inorganic acids, such as ascorbic acid, formic acid, acetic acid, and/or sulphuric acid. ### Claim 6 (depends on 5) A process according to claim 5, wherein the catalyst is a cyclodextrin. ### Claim 7 (depends on 6) A process according to claim 6, wherein the catalyst is alpha-cyclodextrin. ### Claim 8 (depends on 1) A process according to claim 1, wherein 0.0001 to 1.0 molar equivalents of catalyst are present, relative to the compound of formula A. ### Claim 9 (depends on 1) A process according to claim 1, wherein in step (i) the temperature of the reaction is maintained at a temperature of 25° C. or less or 15° C. or less when the oxidising agent is added to the reaction mixture. ### Claim 10 (depends on 1) A process according to claim 1, wherein the cyclodextrin used in step (ii) is selected from one or more of W6 alpha cyclodextrin, a six sugar ring molecule, W7 beta cyclodextrin, a seven sugar ring molecule, W8 gamma cyclodextrin, an eight sugar ring molecule, derivatives thereof, and mixtures thereof. ### Claim 11 (depends on 10) A process according to claim 10, wherein the cyclodextrin used in step (ii) is alpha-cyclodextrin. ### Claim 12 (depends on 11) A process according to claim 11, wherein the mixture is cooled to a temperature within the range of about −8° C. to about 10° C. ### Claim 13 (depends on 11) A process according to claim 11, wherein the mixture is cooled to a temperature within the range of about −5° C. to about 4° C. ### Claim 14 (depends on 11) A process according to claim 11, wherein the molar ratio of sulforaphane to cyclodextrin in the resultant complex is within the range of 0.4:1 to 1:1. ### Claim 15 (depends on 1) A process according to claim 1, wherein the process comprises a further step of recrystallizing the resulting complex. ### Claim 16 (depends on 1) A sulforaphane-cyclodextrin complex obtainable by a process as defined in claim 1, wherein the cyclodextrin used in step (ii) is alpha-cyclodextrin and wherein the sulforaphane and alpha-cyclodextrin are present in the complex in a molar ratio of 0.98:1 to 1:1, and wherein the complex has a purity by HPLC greater than 98%. ### Claim 17 (depends on 16) A method of treating and/or preventing microbial infections and/or cancer, the method comprising administering to an individual in need of such treatment a therapeutically effective amount of a sulforaphane-cyclodextrin complex according to claim 16. ### Claim 18 (depends on 16) A pharmaceutical composition comprising a sulforaphane-cyclodextrin complex according to claim 16 and one or more additional pharmaceutical excipients. ### Claim 19 (depends on 1) A process according to claim 1, wherein in step (i) 1 to 1.5 molar equivalents of oxidizing agent, relative to the compound of formula A, is used. ### Claim 20 (depends on 1) A process according to claim 1, wherein in step (i) 1 to 1.1 molar equivalents of oxidizing agent, relative to the compound of formula A, is used. ### Claim 21 (depends on 16) A sulforaphane-cyclodextrin complex according to claim 16, wherein the purity by HPLC is greater than 98.5%.