Synthetic transtaganolide and basiliolide products, derivatives thereof, and synthesis methods thereof

Abstract

Compounds represented by Formula I are provided that include synthetic transtaganolide and basiliolide products. Derivatives of these compounds and methods of synthesis are also provided.

1 . A compound comprising, a synthetic compound represented by Formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         Y is selected from —OR 9 , —N, R 10 , R 11 , —SR 12 , wherein R 9 , R 10 , R 11 , and R 12  are each independently selected from hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         W is selected from —O, —S, or —NR 21 , wherein R 21  is hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         Z is selected from —O, —S, or —NR 22 , wherein R 22  is hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         R 1 , R 2 , and R 3  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl; 
         R 4 , R 5 , and R 6  are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; and 
         R 7  and R 8  are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; and 
         any two or more adjacent R groups optionally combine to form a ring. 
       
     
     
         2 . The synthetic compound of  claim 1 , wherein R 4 , R 5 , and R 6  are independently selected from —OR 23 , —NR 24 R 25 , SR 26 , wherein R 23 , R 24 , R 25 , and R 26  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl. 
     
     
         3 . The synthetic compound of  claim 1 , wherein R 7  and R 8  are independently selected from SiR 27 R 28 R 29 , wherein R 27 , R 28 , and R 29  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl. 
     
     
         4 . The synthetic compound of  claim 1 , wherein R 4  is hydrogen, —CO 2 Me, —CH 2 OAc or —C(O)N—(CH 3 )(OCH 3 ) and R 5  is methyl. 
     
     
         5 . The synthetic compound of  claim 1 , wherein R 4  is methyl and R 5  is —CO 2 Me, or —CH 2 OAc. 
     
     
         6 . The synthetic compound of  claim 1 , wherein R 7  and R 8  are each independently selected from SiR 27 R 28 R 29 , wherein R 27 , R 28 , and R 29  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl, and wherein two adjacent R 7  and R 8  groups optionally form a ring. 
     
     
         7 . The synthetic compound of  claim 1 , wherein R 7  is hydrogen and R 8  is SiMe 3 . 
     
     
         8 . A method of synthesizing a compound represented by Formula I, comprising:
 reacting a compound represented by Formula II with a compound represented by Formula III,   
       
         
           
           
               
               
           
         
         wherein: 
         Y is selected from —OR 9 , —N, R 10 , R 11 , —SR 12 , wherein R 9 , R 10 , R 11 , and R 12  are each independently selected from hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         M is selected from Li, Na, hydrogen, SiR 13 R 14 R 15 , snR 16 R 17 R 18 , BR 19 R 20 , ZnX 2 , MgX 2 , wherein R 13 , R 14 , R 15 , R 16 , R 17 , and R 18  are each independently selected from hydrocarbyl or substituted hydrocarbyl, R 19  and R 20  are each independently selected from hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted hetero atom-containing hydrocarbyl, and X is any halogen; 
         W is selected from —O, —S, or —NR 21 , wherein R 21  is hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         Z is selected from —O, —S, or —NR 22 , wherein R 22  is hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         R 1 , R 2 , and R 3  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         R 4 , R 5 , and R 6  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; and 
         R 7  and R 8  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl, wherein two or more adjacent R groups optionally combine to form a ring. 
       
     
     
         9 . The method of  claim 8 , wherein reacting the compound represented by Formula II with the compound represented by Formula III, further comprises reacting in the presence of Pd(PPh 3 ) 4  or Pd(Pt—Bu 3 ) 2 . 
     
     
         10 . The method of  claim 9 , wherein reacting the compound represented by Formula II with the compound represented by Formula III, further comprises reacting in the presence of water. 
     
     
         11 . The method of  claim 8 , wherein Formula II is tributyl(2-methoxyethynyl)stannane. 
     
     
         12 . The method of  claim 8 , wherein R 4  is hydrogen, —CO 2 Me, —CH 2 OAc or —C(O)N—(CH 3 )(OCH 3 ), and R 5  is methyl. 
     
     
         13 . The method of  claim 8 , wherein R 4  is methyl, and R 5  is —CO 2 Me, or —CH 2 OAc. 
     
     
         14 . The method of  claim 8 , wherein R 7  and R 8  are each independently selected from SiR 27 R 28 R 29 , wherein R 27 , R 28 , and R 29  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl. 
     
     
         15 . The method of  claim 8 , wherein R 7  is hydrogen, and R 8  is SiMe 3 . 
     
     
         16 . A method of enriching for an enantiomer of Formula I, comprising:
 synthesizing a compound of Formula III in which one of R 7′  and R 8′  is a silyl group and the other of R 7′  and R 8′  is hydrogen;   removing the silyl group to form an enantioselective compound; and   reacting a compound of Formula II with the enantioselective Formula III compound, to form the compound of Formula I.   
       
         
           
           
               
               
           
         
         wherein: 
         Y is selected from —OR 9 , —N, R 10 , R 11 , —SR 12 , wherein R 9 , R 10 , R 11 , and R 12  are each independently selected from hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         M is selected from Li, Na, hydrogen, SiR 13 R 14 R 15 , SnR 16 R 17 R 18 , BR 19 R 20 , ZnX 2 , and MgX 2 , wherein R 13 , R 14 , R 15 , R 16 , R 17 , and R 18  are each independently selected from hydrocarbyl and substituted hydrocarbyl, R 19  and R 20  are each independently selected from hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl, and X is any halogen; 
         W is selected from —O, —S, or —NR 21 , wherein R 21  is hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted hetero atom-containing hydrocarbyl; 
         Z is selected from —O, —S, or —NR 22 , wherein R 22  is hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; 
         R 1 , R 2 , and R 3  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl; and 
         R 4 , R 5 , and R 6  are each independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; and 
         any two or more adjacent R groups optionally combine to form a ring. 
       
     
     
         17 . The method of  claim 16 , wherein the silyl group is SiMe 3 . 
     
     
         18 . The method of  claim 17 , wherein the silyl group is SiMe 3  and Formula III is iodoacid. 
     
     
         19 . A compound, comprising a synthetic compound represented by Formula IV: 
       
         
           
           
               
               
           
         
       
       wherein:
 R a  is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl; 
 W a  is selected from the group consisting of —OR x , —SR xx , and —NR xxx R xxxx , where each of R x , R xx , R xxx  and R xxxx  is independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl; 
 each of R 3  through R 8  is selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl; 
 Z is selected from the group consisting of —O, —S and —NR 22 , wherein R 22  is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl; 
 any two or more of R a  and R 3  through R 8  optionally combine to form a ring. 
 
     
     
         20 . The compound of  claim 19 , wherein R a  is an alkoxy. 
     
     
         21 . The compound of  claim 19 , wherein W a  is —OR x  in which R x  is a silyl ether moiety. 
     
     
         22 . The compound of  claim 21 , wherein the silyl ether moiety is a tert-butyl dimethyl silyl ether moiety or a trimethyl silyl ether moiety. 
     
     
         23 . The compound of  claim 20 , wherein W a  is —OR x  in which R x  is a silyl ether moiety. 
     
     
         24 . The compound of  claim 23 , wherein the silyl ether moiety is a tert-butyl dimethyl silyl ether moiety or a trimethyl silyl ether moiety. 
     
     
         25 . A method of synthesizing a compound of Formula IV, the method comprising reacting a compound of Formula IV-I with a compound of Formula IV-II according to reaction scheme 11 to form the compound of Formula IV: 
       
         
           
           
               
               
           
         
       
       wherein:
 R a  is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl; 
 W a  is selected from the group consisting of —OR x , —SR xx  and —NR xxx R xxxx , where each of R x , R xx , R xxx  and R xxxx  is independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl; 
 each of R 3  through R 8  is selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl; 
 Z is selected from the group consisting of —O, —S and —NR 22 , wherein R 22  is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl; 
 M is selected from the group consisting of Li, Na, hydrogen, SiR 12 R 14 R 15 , SnR 16 R 17 R 18 , BR 19 R 20 , MgX′ 2  and ZnX″ 2 , wherein:
 each of R 13  through R 18  is independently selected from the group consisting of hydrocarbyl, and substituted hydrocarbyl, 
 each of R 19  and R 20  is independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl, and 
 each of X′ and X″ is independently selected from the group consisting of halogens; 
 
 X is a halogen; and 
 any two or more of R a  and R 3  through R 8  optionally combine to form a ring. 
 
     
     
         26 . The method of  claim 25 , wherein R a  is an ethylene moiety or phenyl moiety. 
     
     
         27 . The method of  claim 25 , wherein M is a trialkyl tin moiety or a zinc halide moiety. 
     
     
         28 . The method of  claim 26 , wherein M is a tributyl tin moiety or a zinc chloride moiety.