Pharmaceutical compositions having appetite suppressant activity

Abstract

A pharmaceutical composition contains an extract obtainable from a plant of the genus Trichocaulon or Hoodia containing an appetite suppressant agent having the formula (1). A process for obtaining the extract and a process for synthesizing compound (1) and its analogues and derivatives is also provided. The invention also extends to the use of such extracts and compound (1) and its analogues for the manufacture of medicaments having appetite suppressant activity. The invention further provides novel intermediates for the synthesis of compound (1).

1 . A process for preparing an extract of a plant of the genus Trichocaulon or of the genus Hoodia, the extract comprising an appetite suppressant agent, the process including the steps of treating collected plant material with a solvent to extract a fraction having appetite suppressant activity, separating the extraction solution from the rest of the plant material, removing the solvent from the extraction solution and recovering the extract.  
     
     
         2 . A process as claimed in  claim 1  wherein the plant of the genus Trichocaulon is selected from the species  Trichocaulon piliferum  and  Trichocaulon officinale  and the plant of the genus Hoodia is selected from the species  Hoodia currorii, Hoodia gordonii  and  Hoodia lugardii.    
     
     
         3 . A process as claimed in  claim 1  or  claim 2  which includes the step of concentrating the active agent in the extracted material by further extraction with a solvent.  
     
     
         4 . A process as claimed in  claim 1 ,  claim 2 , or  claim 3 , wherein the solvent in the solvent extraction step or steps is one or more of methylene chloride, water, methanol, hexane, ethyl acetate or mixtures thereof.  
     
     
         5 . A process as claimed in any one of  claims 1  to  4  inclusive which includes the step of concentrating the active agent in the extracted material by chromatographic separation.  
     
     
         6 . A process as claimed in  claim 5  wherein the chromatographic separation employs one or more of chloroform, methanol, ethyl acetate, hexane or mixtures thereof as an eluant.  
     
     
         7 . A process as claimed in  claim 5  or  claim 6  which includes carrying out the chromatographic separation on a column, collecting the eluate in fractions from the column, evaluating the fractions to determine their appetite suppressant activity, and selecting the at least one fraction containing the appetite suppressant agent.  
     
     
         8 . A process as claimed in any of the preceding claims wherein the extract is processed to form a free-flowing powder.  
     
     
         9 . An extract comprising an appetite suppressant agent when produced by a process as claimed in any of the preceding claims.  
     
     
         10 . A composition having appetite suppressant activity comprising the extract claimed in  claim 9 .  
     
     
         11 . A composition as claimed in  claim 10  when admixed with a pharmaceutical excipient, diluent or carrier.  
     
     
         12 . A composition as claimed in  claim 10  or  claim 11  which is prepared in unit dosage form.  
     
     
         13 . The use of an extract as claimed in  claim 9  in the manufacture of a medicament having appetite suppressant activity.  
     
     
         14 . An extract as claimed in  claim 9  for use as a medicament having appetite suppressant activity.  
     
     
         15 . A method of suppressing an appetite by administering to a human or animal an effective dosage of a composition as claimed in  claim 10 ,  claim 11 , or  claim 12 .  
     
     
         16 . A process for preparing an extract of a plant of the genus Trichocaulon or of the genus Hoodia, the extract comprising an appetite suppressant agent, the process including the steps of pressing collected plant material to separate sap from solid plant material and recovering the sap free of the solid plant material to form the extract.  
     
     
         17 . A process as claimed in  claim 16  wherein the extract is dried to form a free-flowing powder.  
     
     
         18 . An extract comprising an appetite suppressant agent when produced by a process as claimed in  claim 16  or  claim 17 .  
     
     
         19 . A composition having appetite suppressant activity comprising the extract as claimed in  claim 18 .  
     
     
         20 . A composition as claimed in  claim 19  when admixed with a pharmaceutical excipient, diluent or carrier.  
     
     
         21 . A composition as claimed in  claim 19  or  claim 20  which is prepared in unit dosage form.  
     
     
         22 . The use of an extract as claimed in  claim 19  in the manufacture of a medicament having appetite suppressant activity.  
     
     
         23 . An extract as claimed in  claim 18  for use as a medicament having appetite suppressant activity.  
     
     
         24 . A method of suppressing an appetite by administering to a human or animal an effective dosage of a composition as claimed in  claim 19 ,  claim 20 , or  claim 21 .  
     
     
         25 . An extract obtainable from a plant of the genus Trichocaulon or of the genus Hoodia which comprises an appetite suppressant agent having the formula  
       
         
           
           
               
               
           
         
       
     
     
         26 . An extract as claimed in  claim 25  wherein the plant of the genus Trichocaulon is selected from the species  Trichocaulon piliferum  and  Trichocaulon officinale  and the plant of the genus Hoodia is selected from the species  Hoodia currorii, Hoodia gordonii  and  Hoodia lugardii.    
     
     
         27 . An extract as claimed in  claim 26  wherein substantially all the non-active impurities have been removed.  
     
     
         28 . An extract as claimed in any one of  claims 25  to  27  inclusive which has been processed to a free-flowing powder.  
     
     
         29 . A composition having appetite suppressant activity comprising the extract as claimed in any one of  claims 25  to  28  inclusive.  
     
     
         30 . A composition as claimed in  claim 29  when admixed with a pharmaceutical excipient, diluent or carrier.  
     
     
         31 . A composition as claimed in  claim 29  or claims  30  which is prepared in unit dosage form.  
     
     
         32 . The use of an extract as claimed in any one of  claims 25  to  28  inclusive in the manufacture of a medicament having appetite suppressant activity.  
     
     
         33 . An extract as claimed in any one of  claims 25  to  28  inclusive for use as a medicament having appetite suppressant activity.  
     
     
         34 . A method of suppressing an appetite by administering to a human or animal an effective dosage of a composition as claimed in  claim 29 ,  claim 30  or  claim 31 .  
     
     
         35 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R alkyl; 
 R 1 ═H, alkyl, tigloyl, benzoyl, or any other organic ester group;  
 R 2  H, or one or more 6-deoxy carbohydrates, or one or more 2, 6-dideoxy carbohydrates, or glucose molecules, or combinations thereof;  
 and in which the broken lines indicate the optional presence of a further bond between C4-C5 or C5-C6.  
 
     
     
         36 . A compound as claimed in  claim 35  wherein there is a bond between C5-C6, R═methyl, R 1 ═tigloyl, R 2 ═3-0-[-β-D-thevetopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranosyl], the compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         37 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 =H, alkyl, tigloyl, benzoyl, or any other organic ester group.  
 
     
     
         38 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 ═H, alkyl, tigloyl, benzoyl, or any other organic ester group.  
 
     
     
         39 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 ═H, alkyl, tigloyl, benzoyl, or any other organic ester group.  
 
     
     
         40 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R alkyl; and 
 R 1  H, alkyl, tigloyl, benzoyl, or any other organic ester group.  
 
     
     
         41 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; 
 R 1 ═H, alkyl, tigloyl, benzoyl, or any other organic ester group.  
 
     
     
         42 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 ═H, alkyl, tigloyl, benzoyl, or any other organic ester group;  
 R 2 ═H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose molecules, or combinations thereof;  
 and in which the broken lines indicate the optional presence of a further bond between C4-C5 or C5-C6.  
 
     
     
         43 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 ═H, alkyl, tigloyl, benzoyl, or any other organic ester group;  
 R 2 ═H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose molecules, or combinations thereof;  
 and in which the broken lines indicate the presence of a further bond between C4-C5 or C5-C6.  
 
     
     
         44 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 ═H, alkyl, tigloyl, benzoyl, or any other organic ester group;  
 R 2 ═H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose molecules, or combinations thereof;  
 and in which the broken lines indicate the optional presence of a further bond between C4-C5 or C5-C6.  
 
     
     
         45 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 ═H, alkyl, tigloyl, benzoyl, or any other organic ester group;  
 R 2 ═H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose molecules, or combinations thereof;  
 and in which the broken lines indicate the optional presence of a further bond between C4-C5, C5-C6 or C14-C15.  
 
     
     
         46 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 ═H, alkyl, tigloyl, benzoyl, any other organic ester group;  
 R 2 ═H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose molecules, or combinations thereof;  
 and in which the broken lines indicate the optional presence of a further bond between C4-C5, C5-C6 or C14-C15.  
 
     
     
         47 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═alkyl; and 
 R 1 ═H, alkyl, tigloyl, benzoyl, any other organic ester group;  
 R 2 ═H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose molecules, or combinations thereof;  
 and in which the broken lines indicate the optional presence of a further bond between C4-C5, C5-C6 or C14-C15; and  
 R 3 ═H, alkyl, aryl, acyl, or glucoxy.  
 
     
     
         48 . A compound having the general structural formula  
       
         
           
           
               
               
           
         
       
       in which R═H, alkyl, aryl, or any steroid possessing a C14 beta hydroxy group, a C12 beta hydroxy functionality, a C17 acyl group, a C5-C6 olefin, or combinations thereof.  
     
     
         49 . A process for the preparation of a steroid intermediate of the formula  
       
         
           
           
               
               
           
         
       
       which includes the steps of 
 (a) treating the compound  
                     
 with a reducing agent to produce a compound 3β, 12β-dihydroxy-20,20-ethylenedioxypregna-5,14-diene of the formula  
                     
 (b) treating compound (23) with N-bromoacetamide (NBA) and a base to produce a compound 3β,12β-dihydroxy-14,15-epoxy-20,20-ethylenedioxypregn-5-ene of the formula  
                     
 (c) treating compound (24) with a reducing agent to produce a compound 3β, 12β, 14β-trihydroxy-20,20-ethylenedioxypregn-5-ene of the formula  
                     
 and (d) treating compound (25) with an acid and water to produce compound (15).  
 
     
     
         50 . A process for the preparation of compound (15) which includes the steps of 
 (a) treating the compound (22) with p-toluenesulfonyl chloride and a base to produce a compound:3,β, 12β-dihydroxy-20,20-ethylenedioxypregna-5,14-diene-3-tosyl-12-acetate of the formula                          (b) treating the compound (26) with potassium acetate in a solvent to produce a compound 6β,12β-dihydroxy-20,20-ethylenedioxy-3,5α-cyclopregnan-14-ene-12-acetate of the formula                          (c) treating the compound (27) with a reducing agent to produce a compound 6β, 12β-dihydroxy-20,20-ethylenedioxy-3,5α-cyclopregnan-14-ene of the formula                          (d) treating the compound (28) with N-bromoacetamide, and a base to produce a compound 6β,12β-dihydroxy-20, 20-ethylenedioxy-14, 15-epoxy-3,5α-cyclopregnane of the formula                          (e) treating the compound (29) with a reducing agent to produce a compound 6β, 12β, 14β-trihydroxy-20,20-ethylenedioxy-3,5β-cyclopregnane of the formula                          and (f) treating compound (30) with an acid and a solvent to produce compound (15).    
     
     
         51 . A process for the preparation of a carbohydrate intermediate in the form of a monosaccharide cymarose moiety which includes the steps of 
 (i) treating the compound of the formula                          with PhSSiMe 3 , ZNI 2  and BU4 +I   31  to produce a compound 4-0-benzoyl-3-0-methyl-6-deoxy-αβ-D-phenylthioaltroside of the formula                          (ii) optionally treating the compound (37) with diethylaminosulphur trifluoride (DAST) to produce a compound 4-0-benzoyl-3-0-methyl-2-phenylthio- 2,6-dideoxy-αβ-D-fluorocymaropyranoside having the formula                          or    (iii) optionally, treating the compound (37) with t-butyldimethylsilylchloride and imidazole in a solvent to produce 4-0-benzoyl-3-0-methyl-2-0-t-butyldimethyside having the formula                          in which Z═TBDMS═t-butyldimethylsilyl;    and (iv) treating the compound (39) with a base to produce the monosaccharide 3-0-methyl-2-0-t-butyldimethylsilyl-αβ-D-phenylthioaltroside having the formula                          in which Z═TBDMS═t-butyldimethylsily.    
     
     
         52 . A process for the preparation of a carbohydrate intermediate in the form of an activated thevetose moiety which includes the steps of 
 (i) treating the compound                          with phenylthiotrimethylsilane and trimethylsilyltrifluoromethanesulphonate to produce a compound 4-0-benzoyl-3-0-methyl-1-phenylthio-6-deoxy-αβ-glucopyranoside having the formula                          (ii) treating the compound (48) with pivaloyl chloride and a solvent to produce a compound 4-0-benzoyl-3-0-methyl-2-0-pivaloyl-1-phenylthio-6-deoxy-αβ-glucopyranoside having the formula                          and (iii) treating the compound (49) with a brominating agent and diethylaminosulphur trifluoride to produce the monosaccharide compound 4-0-benzoyl-3-0-methyl -2-0-pivaloyl-1-fluoro-6-deoxy-β-glucopyranoside occurring as stereoisomers having the formula                          
     
     
         53 . A steroid intermediate of formula (15) when produced by a process as claimed in  claim 49  or  claim 50 .  
     
     
         54 . A carbohydrate intermediate of formula (40) when produced by a process as claimed in  claim 51 .  
     
     
         55 . A carbohydrate intermediate of formula (50 A) or formula (50 B) when produced by a process as claimed in  claim 52 .  
     
     
         56 . A process of coupling a monosaccharide cymarose to a steroid intermediate, which includes the steps of 
 i) reacting a cymarose moiety of formula (38) with a steroid intermediate of formula (15) as claimed in  claim 53  in the presence of tin chloride in a solvent to produce a compound 3-0-[4-0-benzoyl-2-phenylthio-β-D-cymaropyranosyl]-12,14-β-dihydroxy-pregnan-5-ene-20-one of the formula                          and (ii) treating the compound (51) with tiglic acid chloride in pyridine and thereafter with a base to produce a compound 3-0-[4-0-benzoyl-2-phenylthio-β-D-cymaropyranosyl]-12β-tigloyl-14β-)hydroxy-pregnan-5-ene-20-one of the formula                          
     
     
         57 . A compound of formula (52) when produced by a process as claimed in  claim 56 .  
     
     
         58 . A process of coupling a monosaccharide cymarose moiety to a monosaccharide thevetose moiety and coupling the resultant disaccharide to the compound of formula (52) as claimed in  claim 57  which includes the steps of 
 i) coupling a selectively protected cymarose moiety of formula (40) as claimed in  claim 54  and a monosaccharide thevetose moiety of formula (50 A) as claimed in  claim 55  using tin chloride (SnCl 2 ) and silver trifluoromethanesulphonate to produce a compound of the formula  
                     
 in which Z═TBDMS═t-butyldimethylsilyl  
 ii) treating compound (53) with tetrabutylammoniumfluoride to produce a compound of the formula  
                     
 iii) treating compound (54) with diethylaminosulphur trifluoride to produce a compound of the formula  
                     
 iv) reacting compound (55) with compound (52) as claimed in  claim 57  to produce a compound of the formula  
                     
 and (v) treating compound (56) in a Raney-Nickel reaction and thereafter with a base to produce compound (1) as claimed in  claim 36 .  
 
     
     
         59 . A process of forming a trisaccharide and coupling the 5 resultant trisaccharide to a steroid intermediate, which includes the steps of 
 i) coupling a selectively protected cymarose moiety of formula (40) as claimed in  claim 55  and compound (45) using tin (II) chloride, AgOTf, Cp 2 ZrCl 2  to produce a compound of the formula                          in which Z═TBDMS═t-butyldimethylsilyl;    ii) treating compound (57) with tetrabutylammonium fluoride and diethylaminosulphur trifluoride to produce a trisaccharide compound having the formula                          and iii) coupling the trisaccharide of formula (58) with a steroid intermediate of the formula                          using tin (II) chloride, AgOTf, Cp 2 ZrCl 2  to produce compound (1) as claimed in  claim 36 .    
     
     
         60 . A composition having appetite suppressant activity comprising a compound as claimed in any one of claims 35 to 48 inclusive.  
     
     
         61 . A composition as claimed in  claim 60  wherein the compound is the compound of formula (1) as claimed in  claim 36 .  
     
     
         62 . A composition as claimed in  claim 60  or  claim 61  when admixed with a pharmaceutical excipient, diluent or carrier.  
     
     
         63 . A composition as claimed in  claim 60 ,  claim 61 , or  claim 62 , which is prepared in unit dosage form.  
     
     
         64 . The use of a compound as claimed in any one of  claims 35  to  48  inclusive in the manufacture of a medicament having appetite suppressant activity.  
     
     
         65 . The use as claimed in  claim 64  of a compound of formula (1) as claimed in  claim 36 .  
     
     
         66 . A compound as claimed in any one of  claims 35  to  48  inclusive for use as a medicament having appetite suppressant activity.  
     
     
         67 . A compound as claimed in  claim 66  which is the compound of formula (1) as claimed in  claim 36 .  
     
     
         68 . A method of suppressing an appetite by administering to a human or animal an effective dosage of a composition as claimed in any one of  claims 60  to  63  inclusive.  
     
     
         69 . A foodstuff or beverage comprising an effective quantity of a compound as claimed in any one of  claims 35  to  48  inclusive to have an appetite suppressant effect when ingested.  
     
     
         70 . A foodstuff or beverage as claimed in  claim 69  wherein v the compound is the compound of formula (1) as claimed in  claim 36 .  
     
     
         71 . Use of a compound of formula (1) as claimed in  claim 36  isolated from a plant of the genus Trichocaulon or of the genus Hoodia for the manufacture of a medicament having appetite suppressant activity.  
     
     
         72 . Use according to  claim 71  wherein the compound is isolated from the species  Trichocaulon piliferum  or  Trichocaulon officinale  or from the species  Hoodia currorii, Hoodia gordonii  or  Hoodia lugardii.    
     
     
         73 . A composition having appetite suppressant activity comprising a compound of formula (1) isolated from a plant of the genus Trichocaulon or of the genus Hoodia.  
     
     
         74 . A composition as claimed in  claim 73  wherein the compound is isolated and/or purified from a plant of the species  Trichocaulon piliferum  or  Trichocaulon officinale  or from of the species  Hoodia currorii, Hoodia gordonii  or  Hoodia lugardii.    
     
     
         75 . A composition as claimed in  claim 73  wherein the compound is isolated and/or purified from an extract derived from a plant of the species  Trichocaulon piliferum, Trichocaulon officinale  or from a plant of the species  Hoodia currorii, Hoodia gordonii  or  Hoodia lugardii.    
     
     
         76 . A composition as claimed in  claim 73 ,  claim 74 , or  claim 75 , when admixed with a pharmaceutical excipient, diluent or carrier.  
     
     
         77 . A composition as claimed in  claim 76  which is prepared in unit dosage form.  
     
     
         78 . A compound of formula (1) as claimed in  claim 35  isolated from a plant of the genus Trichocaulon or from the genus Hoodia for use as a medicament having appetite suppressant activity.  
     
     
         79 . A compound as claimed in  claim 78  wherein the compound is isolated from a plant of the species  Trichocaulon piliferum  or  Trichocaulon officinale  of from  Hoodia currorii, Hoodia gordonii  or  Hoodia lugardii.    
     
     
         80 . A method of suppressing an appetite by administering to a human or animal an effective dosage of a composition as claimed in any one of  claims 73  to  77  inclusive.  
     
     
         81 . A composition having appetite suppressant activity comprising a melanocortin 4 receptor agonist.  
     
     
         82 . A composition as claimed in  claim 81  wherein the agonist is an extract as claimed in  claim 9 ,  claim 18  or  claim 25 , or a compound as claimed in any one of  claims 35  to  48  inclusive.  
     
     
         83 . A composition as claimed in  claim 81  or  claim 82  wherein the compound is the compound of formula (1) as claimed in  claim 36 .  
     
     
         84 . A composition as claimed in  claim 81 ,  claim 82 , or  claim 83  when admixed with a pharmaceutical excipient, diluent or carrier.  
     
     
         85 . A composition as claimed in any one of  claims 81  to  84  inclusive, which is prepared in unit dosage form.  
     
     
         86 . The use of a melanocortin 4 receptor agonist in the manufacture of a medicament having appetite suppressant activity.  
     
     
         87 . The use as claimed in  claim 86  of an extract as claimed in  claim 9 ,  claim 18  or  claim 25 , or a compound as claimed in any one of  claims 35  to  48  inclusive.  
     
     
         88 . The use as claimed in  claim 87  of a compound of formula (1) as claimed in  claim 36 .  
     
     
         89 . A melanocortin 4 receptor agonist for use as a medicament having appetite suppressant activity.  
     
     
         90 . A melanocortin 4 receptor agonist as claimed in  claim 89  which is an extract as claimed in  claim 9 ,  claim 18  or  claim 25 , or a compound as claimed in any one of  claims 35  to  48  inclusive.  
     
     
         91 . A melanocortin 4 receptor as claimed in  claim 90  which is the compound of formula (1) as claimed in  claim 36 .  
     
     
         92 . A method of suppressing an appetite by administering to a human or animal an effective dosage of a composition as claimed in any one of  claims 81  to  85  inclusive.  
     
     
         93 . The use of a melanocortin 4 receptor agonist to suppress the appetite of and/or to combat obesity in a human or animal.  
     
     
         94 . The use as claimed in  claim 93  of an extract as claimed in  claim 9 ,  claim 18  or  claim 25 , or a compound as claimed in any one of  claims 35  to  48  inclusive.  
     
     
         95 . The use as claimed in  claim 94  of a compound of formula (1) as claimed in  claim 36 .  
     
     
         96 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         97 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         98 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         99 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         100 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         101 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         102 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         103 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         104 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         105 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         106 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         107 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         108 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         109 . A compound occurring as stereo-isomers having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         110 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         111 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         112 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
       in which Z═TBDMS═t-butyldimethylsilyl.  
     
     
         113 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         114 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         115 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         116 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         117 . A compound having the structural formula  
       
         
           
           
               
               
           
         
       
     
     
         118 . A method of combating obesity in a human or animal comprising administering to said human or animal an obesity combating amount of an extract as claimed in any one of claims  9 ,  25 ,  26 ,  27  or  28 .  
     
     
         119 . A method of combating obesity in a human or animal comprising administering to said human or animal an obesity combating amount of a composition as claimed in  claim 10 .  
     
     
         120 . A method of combating obesity in a human or animal comprising administering to said human or animal an obesity combating amount of a compound as claimed in  claim 35  or  36 .  
     
     
         121 . A structure of the formula 3-O-β-D-theverosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside-12β-O-tigloyl-14β-hydroxy-pregnane-5-ene-20-one.