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Synthesis and Application of Four-Membered Carbocycle Amphiphiles

Wantanee Sittiwong, University of Nebraska - Lincoln


Amphiphilic organic compounds, natural and unnatural, have been studied a great deal and applied in a wide range of research areas. We synthesized a new class of modified amphiphiles which incorporate a four-membered carbocycle into the backbone of fatty acids, fatty esters and related skeletons. The modified amphiphiles were investigated for their potential applications in different fields of research including drug development, click chemistry, polymerization, and material science. Tuberculosis is a global disease that affects about one-third of world population caused by the pathogen Mycobacterium tuberculosis (M. tb). The current treatment requires a long course of chemotherapy with the combination of the four most potent drugs (first-line drugs), but the increasing occurrence of current first-line drug resistance has urged the need for the development of novel drugs for the new treatments. We discovered that four-membered carbocycle fatty acids possess high levels of activity in vitro against M. tb. Some of the synthesized analogs displayed equal or more potent inhibition than known drugs, D-cycloserine and isoniazid. The results led to the studies on the metabolic inhibition for future design of better potent anti-tuberculosis drugs. Click chemistry is described as the efficient reactions combining two or more components. We introduced the amphiphilic cyclobutenes as clickable agents for Inverse Electron Demand Diels-Alder cycloaddition (DARinv ), a known click reaction. The data has revealed that the cyclobutenes were as effective as norbornenes, known clickable agents. We next investigated the amphiphilic cyclobutenes as monomers for ring-opening metathesis polymerization. The conditions using the Grubbs' catalysts were studied including the evaluation of the amphiphilic cyclobutenes as silver nanoparticle (AgNP) coating. We revealed that they could stabilize AgNP with similar properties to long-chained fatty acids. In addition, we have designed and synthesized inhibitors for holocarboxylase synthetase (HLCS), a family of biotin protein ligase that catalyzes biotin attachment to proteins including biotin-dependent carboxylases and histone which are essential in the production of proteins and fatty acids. The biotin-5&feet;-AMP based analogs were used as tools to gain mechanistic insight to the enzyme activity. Finally, in the course of previously studies on rhenium (VII) oxides, we improved the methodology and provided mechanistic insights into the conversion of hemiacetals to acetals, thioacetals, and homoallyl ethers using rhenium (VII) oxide as a mild catalyst.

Subject Area

Biochemistry|Organic chemistry|Biomedical engineering|Materials science

Recommended Citation

Sittiwong, Wantanee, "Synthesis and Application of Four-Membered Carbocycle Amphiphiles" (2014). ETD collection for University of Nebraska - Lincoln. AAI3632752.