Production of Furanones

Abstract

The present invention relates to the side chain functionalization of fimbrolides (halogenated 3 -alkyl- 5 -methylene- 2 ( 5 H)-furanones) and their synthetic analogues, that yields fimbrolides substituted with a halogen, an oxygen or a nitrogen functionality in the alkyl chain, especially fimbrolide alcohols, caboxylate and sulfinate and sulfonate esters, ethers, aldehydes, ketones, acids, amides, nitro derivatives, hydrophobic, hydrophilic and fluorophilic alkyl derivatives and polymers.

1 - 26 . (canceled) 
     
     
         27 . A method for forming a fimbrolide derivative, the method including reacting a fimbrolide with a halogenating agent and/or an oxygenating agent to form compounds with formula (Ia): 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, alkyl, alkoxy, oxoalkyl, alkenyl, aryl or arylalkyl whether unsubstituted or substituted, straight chain or branched chain, hydrophobic, hydrophilic or fluorophilic; 
         X is a halogen (X═F, Cl, Br or I), OH, OOH, OC(O)R 1  or ═O; 
         R 2  and R 3  are independently or both hydrogen or halogen; and 
         R 9  is halogen. 
       
     
     
         28 . A method according to  claim 27  wherein the halogenating agent is selected from the group N-bromosuccinimide, N-chlorosuccinimide, N-iodosuccinimide, bromine, cupric bromide, and phenyltrimethylammonium perbromide. 
     
     
         29 . A method according to  claim 27  wherein the oxygenating agent is selected from lead tetraacetate, Rose Bengal/oxygen gas, hydrogen peroxide/vanadium pentoxide, selenium dioxide, and 3-chloroperoxybenzoic acid. 
     
     
         30 . A method for forming a fimbrolide derivative, the method including displacement and/or functionalisation of the halogen or oxygen substituent in the fimbrolide side chain by treating with a nucleophile or an electrophile to form compounds with formula (II): 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, alkyl, alkoxy, oxoalkyl, alkenyl, aryl or arylalkyl whether unsubstituted or substituted, straight chain or branched chain, hydrophobic, hydrophilic or fluorophilic; 
         R 2  and R 3  are independently or both hydrogen or halogen; 
         R 9  is halogen; and 
         R 4  is selected from the group halogen, amine, azide, hydroxyl, thiol, or any hydrophobic, hydrophilic or fluorophilic alkyl, alkoxy, mercaptoalkyl, alkenyloxy, mercaptoalkenyl, aryloxy, mercaptoaryl, arylalkyloxy, mercaptoarylalkyl, OC(O)R 1 , SC(O)R 1 , OS(O)R 1 , OS( 0 ) 2 R 1 , NHC(O)R 1 , OC(O)NHR 1 , or ═O. 
       
     
     
         31 . A method according to  claim 30  wherein the nucleophile is selected from metal halides, water, organic metal carboxylate, organic alcohols, dimethyl sulfoxide, organonitrile/acid catalyst, and silver triflate. 
     
     
         32 . A method according to  claim 30  wherein the electrophile is selected from organic acids, isocyanates, acid halides or active acylating agents such as carbonyl imidazoles or anhydrides (including activated hydrophilic PEG acids, PEG acid chlorides, PEG-oxycarbonylimidazoles and PEG-isocyanates) organic sulfonyl chlorides, and diethylaminosulfur trifluoride. 
     
     
         33 . A fimbrolide derivative produced by the method according to  claim 27  or  claim 30 . 
     
     
         34 . A fimbrolide derivative according to  claim 33 , wherein the fimbrolide derivative is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         35 . An oligomer or polymer comprising a fimbrolide derivative according to  claim 33 . 
     
     
         36 . The polymer according to  claim 35 , wherein the polymer is a homopolymer. 
     
     
         37 . A polymer according to  claim 35 , wherein the polymer is a copolymer comprising one other polymerisable monomers. 
     
     
         38 . A method of inhibiting the growth of microbes comprising treating the microbes with a fimbrolide derivative according to  claim 33 . 
     
     
         39 . A method of inhibiting fouling of a surface comprising treating the surface with a fimbrolide derivative according to  claim 33 . 
     
     
         40 . A fimbrolide derivative selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         41 . A composition comprising a fimbrolide derivative of  claim 40 .