Synthesis of cannabinoids
View Patent ↗The present invention relates to a process for the production of compound (A) comprising reacting compound (B) with compound (C). A further ring closure reaction may be necessary. The invention further relates to certain novel compounds of formula (B).
1. A process for the production of a compound of general formula A:
wherein R c , R d and R e are independently H, alkyl, or substituted alkyl; and R 1 to R 4 are independently H, OH, OR′ (R′ is alkyl, aryl, substituted alkyl or aryl, silyl, acyl, or phosphonate), alkyl, substituted alkyl, aryl, acyl, halide, amine, nitrate, sulphonate or phosphonate;
comprising reacting compound B with compound C:
wherein R a is H, alkyl, aryl, acyl or silyl; R b is alkyl, aryl or acyl; R c , R d , R e and R 1 to R 4 are as hereinbefore defined.
2. A process according to claim 1 , wherein R a is alkyl, aryl or acyl.
3. A process according to claim 1 , wherein R b is an acyl group.
4. A process according to claim 3 , wherein OR b is an ester group selected from the group consisting of acetate, propionate, butyrate, trimethylacetate, phenylacetate, phenoxyacetate, diphenylacetate, benzoate, p-nitrobenzoate, phthalate and succinate.
5. A process according to claim 1 , wherein both R a and R b are acyl groups.
6. A process according to claim 5 , wherein OR a and OR b are ester groups independently selected from the group consisting of acetate, propionate, butyrate, trimethylacetate, phenylacetate, phenoxyacetate, diphenylacetate, benzoate, p-nitrobenzoate, phthalate and succinate.
7. A process according to claim 6 , wherein OR a and OR b are diphenylacetate.
8. A process according to claim 1 wherein R c , R d and R e are methyl.
9. A process according to claim 1 , wherein R 1 is OR″ wherein R″ is H, alkyl, substituted alkyl, acyl or silyl.
10. A process according to claim 9 , wherein R 1 is OH.
11. A process according to claim 1 , wherein R 2 and R 4 are H.
12. A process according claim 1 , wherein R 3 is C 5 H 11 .
13. A process according claim 1 , wherein compound A is Δ 9 -THC, compound B is an ether or ester of (+)-p-menth-2-ene-1,8-diol and compound C is olivetol.
14. A process according to claim 1 , wherein the reaction of compound B with compound C is carried out in the presence of an acid catalyst.
15. A process according to claim 14 , wherein the acid catalyst is nonmetallic.
16. A process according to claim 14 , wherein 0.1–1.5 equivalents of acid catalyst are used.
17. A compound, represented by structure B,
wherein OR a and OR b are independently chosen from acetate, propionate, butyrate, trimethylacetate, phenylacetate, phenoxyacetate, diphenylacetate, benzoate, p-nitrobenzoate, phthalate and succinate (provided that only one of OR a and OR b is acetate), and R c , R d and R e are independently H, alkyl, or substituted alkyl.
18. A compound according to claim 17 , wherein OR a and OR b are diphenylacetate.
19. A process according to claim 1 further comprising performing a ring closure step.
20. A process according to claim 8 , wherein R 1 is OH, R 2 and R 4 are H, and R 3 is C 5 H 11 .
21. A process according to claim 6 , wherein no more than one of OR a and OR b is acetate.