Cannabis extracts and uses thereof

Abstract

The present disclosure concerns a group of cannabinoid compounds defined by formulas (I) to (IV), wherein R1 is —H or —COOH, for the first time isolated and fully characterized in structure, absolute stereochemistry by the present applicant. Methods of isolation, characterization, stereoselective synthesis, biological activity, pharmaceutical compositions and therapeutic applications of the present compounds as modulators of the cannabinoid CB1 receptor are also object of the disclosure.

What is claimed is: 
     
         1 . A cannabinoid compound selected from the group consisting of:
 (−)trans (1R,6R) cannabidibutol [CBDB] of formula (I),   (−)trans (1R,6R) Δ 9  tetrahydrocannabutol [Δ 9  THCB] of formula (II),   (−)trans (1R,6R) Δ 9  tetrahydrocannabiphorol [Δ 9  THCP] of formula (III),   (−)trans (1R,6R) cannabidiphorol [CBDP] of formula (IV)   
       
         
           
           
               
               
           
         
         wherein R 1  is —H, or their corresponding acid derivatives wherein R 1  is —COOH. 
       
     
     
         2 . A method to produce the cannabinoid compound CBDB of formula (I) of  claim 1 , comprising reacting (1S,4R)-1-methyl-4-(prop-1-en-2-yl)cycloex-2-enol with 5-butylbenzene-1,3-diol according to scheme (I) in presence of an acidic catalyst, obtaining CBDB. 
       
         
           
           
               
               
           
         
       
     
     
         3 . A method to produce the cannabinoid compound CBDP of formula (IV) of  claim 1 , comprising reacting (1S,4R)-1-methyl-4-(prop-1-en-2-yl)cycloex-2-enol with 5-heptylbenzene-1,3-diol according to scheme (II) in presence of an acidic catalyst, obtaining CBDP. 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method of  claim 2 , wherein the acidic catalyst is p-toluensulphonic acid. 
     
     
         5 . The method of  claim 3 , wherein the acidic catalyst is p-toluensulphonic acid. 
     
     
         6 . The method of  claim 2 , wherein the reaction is performed under inert atmosphere in a halogenated organic solvent at a temperature of −10±5° C., for a time ranging from 30 to 90 min. 
     
     
         7 . The method of  claim 3 , wherein the reaction is performed under inert atmosphere in a halogenated organic solvent at a temperature of −10±5° C., for a time ranging from 30 to 90 min. 
     
     
         8 . A method to produce the cannabinoid compound Δ 9  THCB of formula (II) of  claim 1 , comprising reacting the CBDB of formula (I) of  claim 1  with hydrochloric acid obtaining (−)trans HCl-THCB of formula (V), 
       
         
           
           
               
               
           
         
         followed by treating the compound (V) with a basic compound, obtaining Δ 9  THCB. 
       
     
     
         9 . A method to produce the cannabinoid compound Δ 9  THCP of formula (III) of  claim 1 , comprising reacting the CBDP of formula (IV) of  claim 1  with hydrochloric acid obtaining (−)trans HCl-THCP of formula (VI), 
       
         
           
           
               
               
           
         
         followed by treating the compound (VI) with a basic compound, obtaining Δ 9  THCP. 
       
     
     
         10 . The method of  claim 8 , wherein said CBDB is in a mixture with (−)trans Δ 8  THCB of formula (VII) (VII) 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 9 , wherein said CBDP is in a mixture with (−)trans Δ 8  THCP of formula (VIII) 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 8 , wherein said basic compound is potassium amylate. 
     
     
         13 . The method of  claim 9 , wherein said basic compound is potassium amylate. 
     
     
         14 . A method of treating a disease mediated by the CB1 receptor comprising administering a compound  claim 1  to a patient in need thereof. 
     
     
         15 . A pharmaceutical composition comprising a compound of  claim 1  in presence of one or more pharmaceutically acceptable excipients.