Investigation of 1, 3- Dipolar Cycloaddition Mechanisms

Lisa Ahlberg (Chemistry)

Investigation of 1,3-Dipolar Cycloaddition Mechanisms: Synthesis of Thiolactomycin and Derivatives

Development of highly antibiotic resistant strains of infections such as staphylococcus and tuberculosis warrant the search for new antibacterial chemotherapies.  With vanishing antibiotic therapies available for such infections and with little pharmaceutical company input into such problems, it is critical for many researchers to investigate novel therapies against these bacterial threats.

This proposal is to fund a student to work on the synthesis of thiolactone compounds, such as thiolactomycin, which has shown selective activity against fatty acid synthase enzymes making it an effective treatment for urinary tract and intraperitoneal bacterial infections.

It is proposed to make compounds similar to Thiolactomycin.  We are interested in the 1,3-dipolar cycloaddition reaction. We would like to investigate the changes in the substituents will have on the resulting regiochemistry and whether these changes can result in a new antibiotic.

Previous experience with isoxazoline as 1,3-dipolar cycloaddition chemistry has shown that structures similar to compounds can be synthesized.  We have also found that Thiobenzophenone –S-methylide reactions with carbonyl or thiocarbonyl compounds can do similar cycloaddition chemistry.  We propose to work toward the thiolactone types of molecules while we study the electronic processes that govern the product mixture in the cyclization process. 

 
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