Aziridine spinosyn derivatives and methods of making

Abstract

Compositions including derivatives of spinosyns and methods for the production of derivatives of spinosyns are provided. The spinosyn derivatives described herein include those functionalized on the C-5,6 double bond to provide an aziridine ring system. The method produces spinosyn derivatives that exhibit activity towards insects, arachnids, and nematodes and are useful in the agricultural and animal health markets.

What is claimed is: 
     
         1 . A spinosyn compound of the following formulas: 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein: 
            is a single bond or a double bond; 
         A is selected from the group consisting of substituted or unsubstituted carbonyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; 
         B is selected from the group consisting of substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; 
         C is O or NH; 
         X 1 , X 2 , X 3 , X 4  and X 5  are each independently selected from N, NR, CR, and CR 2 , wherein X 5  may alternatively be a direct bond and when X 5  is a direct bond, one of X 1 , X 2 , X 3 , and X 4  may be further selected from O or S, wherein each R is selected from hydrogen, hydroxyl, substituted or unsubstituted amino, substituted or unsubstituted thio, substituted or unsubstituted alkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. 
       
     
     
         2 . The spinosyn compound of  claim 1 , wherein when X 1  and X 2  are selected from NR, CR, and CR 2 , the R groups of X 1  and X 2  combine to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. 
     
     
         3 . The spinosyn compound of  claim 1 , wherein when X 2  and X 3  are selected from NR, CR, and CR 2 , the R groups of X 2  and X 3  combine to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. 
     
     
         4 . The spinosyn compound of  claim 1 , wherein A comprises forosamine. 
     
     
         5 . The spinosyn compound of  claim 1 , wherein B comprises rhamnose or a (2R,5S)-5-ethoxy-3,4-dimethoxy-6-methyloxy group. 
     
     
         6 . The spinosyn compound of  claim 1 , wherein A is forosamine, B is rhamnose, C is O, X 1  is N, X 2  is C(CH 3 ), and X 3  is S. 
     
     
         7 . The spinosyn compound of  claim 1 , wherein the spinosyn compound is (1S,2R,8R,10S,12S,13R,17R,18S,22S)-18-{[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy}-22-ethyl-5,17-dimethyl-10-{[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy}-23-oxa-6-thia-4-azapentacyclo[13.10.0.0 2 , 13 .0 3 , 7 .0 8 , 12 ]pentacosa-3(7),4,14-triene-16,24-dione. 
     
     
         8 . The spinosyn compound of  claim 1 , wherein A is forosamine, B is rhamnose, C is O, X 1  is N, X 2  is C(NH 2 ), and X 3  is S. 
     
     
         9 . The spinosyn compound of  claim 1 , wherein the spinosyn compound is (1S,2R,8R,10S,12S,13R,17R,18S,22S)-5-amino-18-{[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy}-22-ethyl-17-methyl-10-{[(2R,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy}-23-oxa-6-thia-4-azapentacyclo[13.10.0.0 2 , 13 .0 3 , 7 .0 8 , 12 ]pentacosa-3(7),4,14-triene-16,24-dione. 
     
     
         10 . A formulation, comprising at least one spinosyn compound of  claim 1  and an acceptable carrier. 
     
     
         11 . The formulation of  claim 10 , further comprising at least one additional active ingredient. 
     
     
         12 . The formulation of  claim 10 , further comprising at least one plant or plant product treatment compound. 
     
     
         13 . The formulation of  claim 11 , wherein the at least one additional active ingredient comprises an insecticide or a miticide. 
     
     
         14 . The formulation of  claim 13 , wherein the insecticide is a contact-acting insecticide. 
     
     
         15 . The formulation of  claim 13 , wherein the miticide is a contact-acting miticide. 
     
     
         16 . A method for controlling pests, comprising contacting a pest with an effective amount of a spinosyn compound of  claim 1 . 
     
     
         17 . The method of  claim 16 , wherein the pest is an insect. 
     
     
         18 . The method of  claim 16 , wherein the pest is an arachnid. 
     
     
         19 . The method of  claim 16 , wherein the pest is a nematode. 
     
     
         20 . A method for making a spinosyn compound, comprising reacting the C-5,6 double bond of Spinosyn A to form a spinosyn compound according to  claim 1 , wherein the spinosyn compound forms via either an epoxide or an 1,2-dihalo intermediate or directly via nitrene insertion into the double bond.