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Surface acoustic waves in chemistry and the total synthesis of the pervilleines
thesisposted on 2017-03-22, 01:31 authored by Kulkarni, Ketav Prakash
Chapter one provides background information on the physical basis and design principles of SAW-based devices. Specifically, it explains the transmission of SAWs through viscous fluids, fabrication of the SAW devices, and the underlying physics in determining the resonant frequency of the SAW device. SAWs are analogous to earthquake waves which travel on the surface of a piezoelectric substrate at the speed of sound. Generation of SAWs was accomplished by using a pair of metal electrodes called IDTs. Micro-fabrication methods, involving sputtering and photolithography, were used to fabricate the SAW devices. The devices were then tested for their resonant frequency by impedance analysis. Chapter two describes the use of SAWs as an energy source for drop-scale chemical reactions. Chemical reagents were loaded on the surface of a piezoelectric substrate in the form of a drop. SAWs were generated on the substrate surface by applying a sinusoidal oscillating electrical signal to a pair of IDTs. The viscous reaction fluid absorbed the SAWs, producing an internal streaming pattern within the reaction drop. Turbulent flow generated by this streaming resulted in heating and stirring of the drop. Chapter two also illustrates the use of SAWs as an energy source in implementing batch process chemistry on a laboratory scale. The reactions were carried out in a closed-vessel glass reactor, typically a flat-bottomed and screw-capped vial. A liquid couplant was employed to enhance the transfer of SAW energy from the piezoelectric substrate to the reaction vessel. Under these conditions, the SAWs were transmitted into the liquid couplant, as bulk sound waves, which facilitated the propagation of Lamb waves in the base of the reaction vessel. These Lamb waves then transmitted the acoustic energy into the reaction solution within the vessel. A range of diverse reactions were attempted using this lab-on-a-chip setup utilising SAWs as the source of energy. Chapter three outlines a new modality for in-gel sample processing and tryptic digestion of proteins using a SAW device. Sample preparation, rehydration, in situ digestion and peptide extraction from gel slices or spots was accelerated by placing the material on a piezoelectric substrate and treating the gel slice, immersed in reagent solutions, with SAWs. The SAW assisted in-gel digestion produced chromatograms of similar coverage and intensity to those observed for traditional processing and overnight digestion in only 30 min. Chapter four describes the enantioselective synthesis of pervilleine C, exploiting aspects of the [4+3] cycloaddition and Brown’s enantioselective oxidative hydroboration. Esterification then completed total syntheses of pervilleine C and its enantiomer. These short syntheses provide an expedient route to pervilleine and select analogues to assist in the elucidation of the pervilleine pharmacophore, and to afford sufficient quantities of the pervilleines for their biological evaluation as MDR reversal agents in MDR cancer cell lines.