Toward a unified synthesis of tetrahydro-α-carboline based natural products and modular synthesis and characterization of multifunctionalized Fe3O4 nanoparticles: application in gene delivery and synthesis of very long chain polyunsaturated fatty acids (VLC-Pufa) and administration in mouse model of STGD3 and AMD

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Title Toward a unified synthesis of tetrahydro-α-carboline based natural products and modular synthesis and characterization of multifunctionalized Fe3O4 nanoparticles: application in gene delivery and synthesis of very long chain polyunsaturated fatty acids (VLC-Pufa) and administration in mouse model of STGD3 and AMD
Publication Type dissertation
School or College College of Science
Department Chemistry
Author Rallabandi, Rameshu
Date 2018
Description Tetrahydro-α-carbolines are present in many natural products. Our efforts to this class were focused on developing a unified synthetic approach to access all classes of tetrahydro-α-carboline containing natural products. We developed an iodohexahydropyridoindolone using an oxidative cyclization of a piperidone derivative with N-iodosuccinimide. Iodohexahydropyridoindolones were subsequently utilized in the synthesis of core compounds for the kapakahines and chaetominine. We also explored reaction of iodohexahydropyridoindolone radical coupling to give quaternary substituted indolines. Super paramagnetic iron oxide nanoparticles (SPION) have received tremendous attention for their unique physiochemical properties and their applications in biomedical research. Fe3O4 nanoparticles have been employed as magnetic resonance imaging (MRI) contrast agents, in targeted drug delivery, in gene therapy, and in separation and in the analysis of cells. While naked nanoparticles are toxic and susceptible to aggregation, surface functionalized particles are suitable for biomedical research. In addition, the properties of the nanoparticle can be tuned by ligand modifications. Modifiable properties include solubility, surface charge, toxicity and magnetic strength. To the best of our knowledge, multifunctionalized Fe3O4 nanoparticles were synthesized using post-synthetic modifications. Herein, we have shown the synthesis of the multifunctionalized Fe3O4 nanoparticles in a simpler and more reproducible fashion. We also developed tools to measure the amount of ligands on multifunctional Fe3O4 nanoparticles. We have shown DNA transfection using these nanoparticles. Very long-chain polyunsaturated acids (VLC-PUFAs) are a class of nondietary polyunsaturated fatty acids with more than 24 carbons. VLC-PUFAs have been found in the retina, brain and testes. Biologically, the ELOVL4 enzyme is known to synthesize VLC-PUFAs in vivo. Genetic defects in ELOVL4 are responsible for dominant Stargardt disease 3 (STGD3). AMD patients have also shown low levels of VLC-PUFA. Strategies to efficiently synthesize VLC-PUFAs are not available. We have developed the methodology for the synthesis of VLC-PUFA C32:6n-3 from docosahexaenoic acid (DHA).
Type Text
Publisher University of Utah
Subject Organic chemistry
Dissertation Name Doctor of Philosophy
Language eng
Rights Management (c) Rameshu Rallabandi
Format application/pdf
Format Medium applcation/pdf
ARK ark:/87278/s6rv5xdd
Setname ir_etd
ID 1539038
Reference URL https://collections.lib.utah.edu/ark:/87278/s6rv5xdd
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