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I. Synthesis of Biosynthetic Intermediates. II. Synthesis of Functionalized Phosphonic Acid Amphiphiles. III. Organic Peroxide Reduction and Reductive Activation

Andrew Scott Olson, University of Nebraska - Lincoln


Methicillin-resistant Staphylococcus aureus (MRSA) is an antibiotic resistant bacterium that commonly infects humans. In recent years a new cyclic lipodepsipeptide known as WAP-8294A has been gaining attention as a new antibiotic to combat MRSA. As part of our efforts to understand and exploit these biosynthetic pathways, we are preparing β-OH-fatty acids analogs of proposed biosynthetic intermediates as N-acetyl cysteamine (SNAC) thioester. The enantioselective synthesis of the substrates is achieved in four steps from commercially available methyl acetoacetate. The polyketide dihydromaltophilin (HSAF), which was identified and isolated from bacterium Lysobacter enzymogenes, is of interest due to it use in crop protection. In collaboration with Prof. Liangcheng Du and coworkers, we have been interested in the biosynthetic pathways responsible for synthesis of the complex HSAF structure. We have been synthesizing analogs of proposed biosynthetic precursors of HSAF in the hope that their incorporation into the biosynthetic pathways will provide us with information about the identity and function of specific genes within the organism. The presentation will discuss a general synthesis of S-(2-acetamidoethyl) (2E,4E,6E,8E,10E)-dodeca-2,4,6,8,10-pentaenethioate. Amphiphilic organic compounds play a vital role in a myriad of applications. One important application is in the fabrication of electrochemical gold thiolate biosensors. Typically self assembled monolayers (SAM) generated from single chain amphiphiles are used for metal passivation and bioprobe immobilization in biosensor applications. These single chain amphiphiles have frequently been functionalized with thiols and are mainly useful for formation of SAMs on gold surfaces. Our work focuses on use of phosphonic acid amphiphiles, which are capable of multipoint interactions with metal oxide surfaces to generate very robust SAMs. This work will describe our preparation of phosphonic acid amphiphiles and describe their initial surface characterization in the labs of our collaborators. In addition to the development of these single chain phosphonic acids amphiphiles we also describe synthetic efforts towards twin chain amphiphiles possessing multiple phosphonate head groups. The O-O peroxide bond is generally portrayed as being very reactive and prone to cleavage. However, literature reports as well as our own findings demonstrate that the peroxide bond of dialkyl peroxides is generally unreactive towards mild reducing agents and nucleophiles. In order to find reagents able to break the O-O bond under mild conditions, we investigated the reactivity of a range of peroxides towards thiols and selenides. Activated peroxides like peresters and a monoperoxyacetal can be reduced by thiolates and phenylselenide. Unhindered dialkyl peroxides can be reduced very slowly by thiolates and phenylselenides. More hindered peroxides, like alkyl tert butyl peroxides as well as triacetone triperoxide (TATP) and diacetone diperoxide (DADP), are unreactive towards any of the reagents at room temperature. We found that the combination of thiols and a catalyst we have prepared. forms a reactive intermediate which, which when used with additional thiol or an added hydride reductant, appears to catalyze the reduction of most peroxides tested; the only peroxide resistant to this reagent system was a bis tert alkyl peroxide. Overall, our discovery will provide new pathways for reduction and reductive activation of the O-O bond of peroxides.

Subject Area

Chemistry|Organic chemistry

Recommended Citation

Olson, Andrew Scott, "I. Synthesis of Biosynthetic Intermediates. II. Synthesis of Functionalized Phosphonic Acid Amphiphiles. III. Organic Peroxide Reduction and Reductive Activation" (2018). ETD collection for University of Nebraska-Lincoln. AAI10793332.