Method of synthesising sulforaphane
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.
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 the oxidizing agent is hydrogen peroxide or a water soluble or miscible organic per-acid, or a mixture thereof.
2. A process according to claim 1 , wherein the solvent used in step(i) and step(ii) is water.
3. A process according to claim 1 , wherein the oxidizing agent is hydrogen peroxide.
4. A process according to claim 1 , wherein the catalyst is selected from cyclodextrin and organic or inorganic acids.
5. A process according to claim 4 , wherein the catalyst is a cyclodextrin.
6. A process according to claim 5 , wherein the catalyst is alpha-cyclodextrin.
7. 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).
8. 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 oxidizing agent is added to the reaction mixture.
9. 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.
10. A process according to claim 9 , wherein the cyclodextrin used in step (ii) is alpha-cyclodextrin.
11. A process according claim 10 , wherein the mixture is cooled to a temperature within the range of about −8° C. to about 10° C.
12. A process according claim 10 , wherein the mixture is cooled to a temperature within the range of about −5° C. to about 4° C.
13. A process according to claim 10 , wherein the molar ratio of sulforaphane to cyclodextrin in the resultant complex is within the range of 0.4:1 to 1:1.
14. A process according to claim 1 , wherein the process comprises a further step of recystallizing the resulting complex.
15. A process according to claim 1 , wherein the catalyst is selected from ascorbic acid, formic acid, acetic acid, and/or sulphuric acid.
16. 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 the catalyst is selected from cyclodextrin and organic or inorganic acids.
17. A process according to claim 16 , wherein the solvent used in step(i) and step(ii) is water.
18. A process according to claim 16 , wherein the oxidizing agent is hydrogen peroxide.
19. A process according to claim 16 , wherein the catalyst is a cyclodextrin.
20. A process according to claim 19 , wherein the catalyst is alpha-cyclodextrin.
21. A process according to claim 16 , wherein 0.0001 to 1.0 molar equivalents of catalyst are present (relative to the compound of formula A).
22. A process according to claim 16 , 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 oxidizing agent is added to the reaction mixture.
23. A process according to claim 16 , 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.
24. A process according to claim 23 , wherein the cyclodextrin used in step (ii) is alpha-cyclodextrin.
25. A process according claim 24 , wherein the mixture is cooled to a temperature within the range of about −8° C. to about 10° C.
26. A process according claim 24 , wherein the mixture is cooled to a temperature within the range of about −5° C. to about 4° C.
27. A process according to claim 24 , wherein the molar ratio of sulforaphane to cyclodextrin in the resultant complex is within the range of 0.4:1 to 1:1.
28. A process according to claim 16 , wherein the process comprises a further step of recystallizing the resulting complex.
29. A process according to claim 16 , wherein the catalyst is selected from ascorbic acid, formic acid, acetic acid, and/or sulphuric acid.