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Studies in Carbohydrate Synthesis: Selective Oxidative Glycosylation of Anomeric Stannanes, Synthesis of Rare Sugars From the Head-to-Tail Swapping Strategy
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Studies in Carbohydrate Synthesis: Selective Oxidative Glycosylation of Anomeric Stannanes, Synthesis of Rare Sugars From the Head-to-Tail Swapping Strategy. |
| 개인저자 | Yang, Tianyi. |
| 단체저자명 | University of Colorado at Boulder. Chemistry. |
| 발행사항 | [S.l.]: University of Colorado at Boulder., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 173 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781088378953 |
| 학위논문주기 | Thesis (Ph.D.)--University of Colorado at Boulder, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Walczak, Maciej A. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | Carbohydrates, one of the most important biomolecules that participate in a myriad of processes in the living organisms, have gained an increasing amount of focus in recent years. Yet, the research of carbohydrates is massively restrained by the accessibility of these complicated molecules. While the enzymatic/biochemical synthesis of carbohydrates is slowly evolving, the chemical synthesis remains the most efficient and universal method in preparing carbohydrates and glycoconjugates. Chapter 1 provides a general background of carbohydrate synthesis and outlines the current synthetic strategies of stereoselective glycosylation. Traditional glycosylations rely heavily on the substrate or reagent to achieve the stereochemical control, leading to a limited scope of applicability. Our solution to this old problem, however, concentrates on the anomeric nucleophiles - glycosyl stannanes, which enables a completely distinct mechanistic pathway and allows for exclusive stereochemical control with less dependence on the substrate structures and a broader scope of applications. This dissertation encompasses three independent projects in the field of methodology development in carbohydrate synthesis based on glycosyl stannanes. The first project (Chapter 2) collects the reactions to prepare the stannanes at the anomeric position of common pyranoses, and reports studies in the optimization, derivatization and exploration of the existing methods to build a library of the readily available nucleophilic glycosyl donors. Major mechanistic pathways include the nucleophile/electrophilic displacement, epoxide opening and the carbene insertion. Upon the formation of the anomeric stannanes, the compatibility of different protecting groups and substituents is studied as well as various protecting/deprotecting conditions. We also discovered a general correlation in the 119Sn-13C coupling constants with the configuration of the anomeric stannanes, allowing for a rapid assignment of anomeric configuration of the complex saccharides.Building on the successful establishment of the stannane synthesis, the second project (Chapter 3) summarizes our efforts in the discovery and development of highly stereoselective oxidative glycosylation using hypervalent iodine reagents as the oxidants. This method couples a C2-OH stannane as the glycosyl donor with a carboxylate or an alcohol as the glycosyl acceptor, which results in an exclusive 1,2-trans selectivity with moderate to high yields. Unlike most of the established glycosylation methods, this reaction works at room temperature and allows the use of a glycosyl donor bearing free hydroxyl group without sacrificing the yield or selectivity. These features present a great advantage in orthogonal/sequential glycosylation and automated saccharide synthesis. Having the different substitution patterns of anomeric stannanes also allowed us to investigate more advanced applications. The third project (Chapter 4) reports the synthesis of L-hexoses and rare D-hexoses from an unprecedented stereoretentive head(C1)-to-tail(C5) swapping strategy. The method is comprised of two key steps: the homologation of the C1 position and the oxidative cleavage of C5-C6. The homologation of the C1 position is achieved by a stereoretentive C-acyl glycosylation with the anomeric stannanes, adding a one-carbon unit that can be readily converted to hydroxymethyl (aldose), methyl (6-deoxyaldose) or ester (uronic acid) in a later stage. On the other hand, the C6 position is deprotected to reveal the free alcohol, which is converted to acyl azide to trigger the Curtius rearrangement resulting in the cleavage of C5-C6 and a new anomeric isocyanate. The isocyanate is subsequently hydrolyzed under acidic condition to provide the anomeric alcohol, concluding the reaction sequence. In contrast to the reported methods, our method takes advantage of the stereochemistry of C1 position and directly translate it to the new C5 position with high fidelity, paving a path to a great number of rare sugars and benefiting the research such as glycoprotein crystallography and natural product synthesis. Taken together, the development of the efficient synthesis around the anomeric stannanes greatly enriched the chemical glycosylation repertoire and pioneered the stereoselective glycosylation with anomeric nucleophiles, representing a milestone in synthetic carbohydrate chemistry. |
| 일반주제명 | Organic chemistry. Biochemistry. |
| 언어 | 영어 |
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