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oai:www.ideals.illinois.edu:2142/49809 2023-07-11 col_2142_14789 col_2142_5131 com_2142_14788 com_2142_8903 com_2142_5130

Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2014-04-15T20:00:36Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Sisco_Seiko.pdf: 39731093 bytes, checksum: c5a677f96924a2150cc9bc68dfe0cc54 (MD5) Made available in DSpace on 2014-05-30T17:18:47Z (GMT). No. of bitstreams: 2 Seiko_Sisco.pdf: 36333261 bytes, checksum: e18aec381e3a12e6c3ca9f403f75d418 (MD5) license.txt: 4059 bytes, checksum: 846ce43eff6c8ab7c55e35f9bf1d76fb (MD5) Restriction data tranferred 2014-07-01T11:39:43-05:00 Original Data Group with Access Administrator Release Date: 2016-05-30 12:21:23 UTC Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system reversed-polarity iterative cross-coupling (RP-ICC) Item marked as restricted to the 'Administrator' Group (id=1) by Seth Robbins (robbins.sd@gmail.com) on 2014-05-30T17:21:34Z Item is restricted until 2016-05-30T17:21:23Z Limited Restriction Lifted for Item 49860 on 2016-09-22T20:59:31Z. http://hdl.handle.net/2142/49809 en Copyright 2014 Seiko Fujii Sisco small molecule iterative cross-coupling (ICC) Burke, Martin D. Burke, Martin D. Imlay, James A. Katzenellenbogen, John A. van der Donk, Wilfred A. Sisco, Seiko 2014-05-30T17:18:47Z 2014-05-30T17:18:47Z 2016-09-22T20:59:31Z 2014-05 2014-05-30T17:18:47Z 2014-05 Small molecules perform an extraordinary range of important functions. Major advances have been achieved in the laboratory synthesis of small molecules, yet most synthetic efforts are specialized for each target, making synthesis a complex and time-intensive process reserved for specialists. Instead, a general and automated synthesis strategy could provide the broader scientific community rapid access to small molecules for functional studies. To achieve this goal, this dissertation describes the advances toward expanding and automating the iterative cross- coupling (ICC) strategy with N-methyliminodiacetic acid (MIDA) boronate building blocks, an analogous approach to how Nature makes small molecules by iterative assembly of bifunctional building blocks. With the ultimate goal of understanding and optimizing the promising antilipoperoxidant activity of carotenoid natural products, the first total synthesis of synechoxanthin was accomplished. The synthesis was enabled by the development of a new methodology for small molecule synthesis termed reversed-polarity iterative cross-coupling (RP-ICC), in which the polarity of the building blocks is reversed to match the preferred polarity for Suzuki-Miyaura cross-coupling. This strategy expanded the scope and flexibility of ICC by increasing the number of building blocks that can be utilized in the same platform. With an efficient method to access this small molecule, the antilipoperoxidant activity of synechoxanthin was investigated in a chemically-defined liposome system. Preliminary studies indicated that synechoxanthin is an antilipoperoxidant with similar activity to the carotenoid gold standard astaxanthin. To further simplify and generalize the synthesis of small molecules, the ICC strategy was automated through the development of a small molecule synthesizer. Key to this advance was the discovery that MIDA boronates can be purified via a novel type of catch-and-release chromatography. Many different types of small molecules, including materials, pharmaceuticals, and a range of complex natural products and their derivatives were prepared via the fully automated iterative assembly of MIDA boronate building blocks. Contemporaneously with the development of the synthesizer, the ICC platform was expanded to include C-N and Csp3-Csp2 bond formations. Collectively, these advances seek to establish the foundation for a general and automated platform for small molecule synthesis to ultimately help shift the rate-limiting step in small molecule science from synthesis to functional studies. total synthesis carotenoid natural product synechoxanthin antilipoperoxidant automation methyliminodiacetic acid (MIDA) boronate Expansion and automation of iterative cross-coupling: total synthesis of synechoxanthin and development of a small molecule synthesizer text Chemistry 1413 Chemistry 0335 University of Illinois at Urbana-Champaign Dissertation Ph.D. PHD:Chemistry -UIUC 10KS0335PHD