Photochemical process for producing artemisinin

1. A process for preparing artemisinin, comprising the steps of:

preparing a mixture comprising (i) a dihydroartemisinic acid derivative of formula (I)

wherein

X is O

Y is formula (II)

R 1 is hydrogen; a C 1 -C 12 alkyl group which is linear or branched or a C 3 -C 10 cycloalkyl group, said alkyl group being unsubstituted or substituted by one or more substituent(s) selected from a C 1 -C 6 alkyl group and a halogen; a trifluoromethyl group; a cycloalkylalkyl group where cycloalkyl and alkyl are as defined above; a C 2 -C 12 alkenyl group which is linear or branched, said alkenyl group being unsubstituted or substituted by one or more substituent(s) selected from a C 1 -C 6 alkyl group and a halogen; a C 5 -C 14 aryl or heteroaryl group, said aryl or heteroaryl group being unsubstituted or substituted by one or more substituent(s) selected from a C 1 -C 6 alkyl group and a halogen; an arylalkyl group where aryl and alkyl are as defined above; or a heteroarylalkyl group where heteroaryl and alkyl are as defined above;

R 3 is OR 1 where R 1 is as defined above;

(ii) at least one organic solvent and (iii) a photosensitizer,

subjecting said mixture to photooxidation by means of a light source, and

recovering the artemisinin thus obtained.

2. The process of claim 1 , wherein the dihydroartemisinic acid derivative has the formula (Ia)

in which X and Y are as defined in claim 1 .

3. The process according to claim 1 or 2 , wherein the at least one organic solvent is selected from the group consisting of alcohols, chlorinated solvents, ketones, sulfoxides, nitriles, N,N-disubstituted amines, esters, nitrogenated heterocycles, ethers, alkanes, aromatic solvents, and mixtures thereof.

4. The process according to claim 1 or 2 , wherein the at least one organic solvent is dichloromethane.

5. The process according to claim 1 or 2 , wherein the organic solvent comprises a polar solvent and the polar solvent is used in a ratio of about 4 to 20 volumes with respect to the dihydroartemisinic acid derivative of formula (I) or (Ia).

6. The process according to claim 1 or 2 , wherein the photosensitizer is selected from Rose bengal, tetraphenylporphyrin, tetraphenylporphyrin derivatives, tetramethylthionine chloride (methylene blue) and toluidine blue.

7. The process according to claim 1 or 2 , wherein the photosensitizer is used in a molar ratio of about 0.000001 to 1 equivalent with respect to the dihydroartemisinic acid derivative of formula (I) or (Ia).

8. The process according to claim 1 or 2 , wherein the mixture comprises an acid catalyst.

9. The process according to claim 8 , wherein the acid catalyst is present in an amount of 0.5 equivalent per equivalent of compound of formula (I) or (Ia).

10. The process according to claim 8 , wherein the acid catalyst is a protic acid.

11. The process according to claim 8 , wherein the acid catalyst is trifluoroacetic acid.

12. The process according to claim 1 or 2 , wherein it comprises the steps of:

preparing a mixture comprising (i) a dihydroartemisinic acid derivative of formula (I) or (Ia) as defined in claim 1 or 2 , (ii) at least one organic solvent, and (iii) a photosensitizer at ambient temperature,

cooling the reaction mixture to a temperature in the range of about −78° C. to ambient temperature with air or oxygen bubbling into it,

adding a catalytic amount of an acid catalyst,

switching the light source on,

maintaining the reaction mixture at the same temperature for 3 h to 24 h,

warming up the reaction mixture to a temperature in the range of about 5 to 15° C. for 2 to 4 hours, and then to a higher temperature in the range of about 15 to 25° C. for 1 to 3 hours,

stopping the reaction,

maintaining the reaction mixture at a temperature in the range of about 15° C. to 25° C. for 1 to 3 hours, and

recovering the artemisinin thus obtained.

13. The process according to claim 12 , wherein the acid catalyst is chosen from protic acids or Lewis acids.

14. The process according to claim 12 , wherein:

the first cooling step is carried out at a temperature between −5° C. and −20° C.;

during the warming up step, the reaction mixture is warmed up to 10° C. for 2 h, and then to ambient temperature for 1 hour, or

after stopping the reaction, the reaction mixture is maintained at ambient temperature for 2 h.

15. The process according to claim 12 , further comprising further purifying the recovered artemisinin.

16. The process according to claim 1 or 2 , wherein the artemisinin is recovered by precipitation and isolation in an alkane/alcohol mixture.

17. The process according to claim 16 , wherein the alkane is selected from n-heptane, n-hexane, cyclohexane, n-pentane, and CMC; and the alcohol is selected from ethanol and isopropanol.