Synthesis of cannabinoids

Abstract

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 . The process according to  claim 1 , wherein R a  is alkyl, aryl or acyl.  
   
   
       3 . The process according to  claim 1 , wherein R b  is an acyl group.  
   
   
       4 . The 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 . The process according to  claim 1 , wherein both of R a  and R b  are acyl groups.  
   
   
       6 . The 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 . The process according to  claim 6 , wherein OR a  and OR b  are diphenylacetate.  
   
   
       8 . The process according to  claim 1 , wherein R c , R d  and R e  are methyl.  
   
   
       9 . The process according to  claim 1 , wherein R 1  is OR″ wherein R″ is H, alkyl, substituted alkyl, acyl or silyl.  
   
   
       10 . The process according to  claim 9 , wherein R 1  is OH.  
   
   
       11 . The process according to  claim 1 , wherein R 2  and R 4  are H.  
   
   
       12 . The process according to  claim 1 , wherein R 3  is C 5 H 11 .  
   
   
       13 . The process according to  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 . The 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 . The process according to  claim 14 , wherein the acid catalyst is nonmetallic.  
   
   
       16 . The process according to  claim 14 , wherein 0.1-1.5 equivalents of acid catalyst are used.  
   
   
       17 . The process according to  claim 1 , further comprising performing a ring closure step.  
   
   
       18 . The 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 .  
   
   
       19 . The process according to  claim 6 , wherein no more than one of R a  and R b  is acetate.