Transition Metal Catalyzed Reactions Of Carbohydrates

Author : Xiaolei Li (Ph.D.)
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (139 download)

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Download or read book Development of Transition Metal-catalyzed Site-selective Carbohydrate Functionalization Reactions and Tissue-selective Protein Degraders written by Xiaolei Li (Ph.D.) and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Carbohydrates are synthetically challenging molecules with vital biological roles in all living systems. To better understand the biological functions of this fundamentally important class of molecules, novel methodologies are urgently needed in two different directions: building block synthesis and selective glycosylation. During my Ph.D. study, I developed two different methodologies for building block synthesis, which could simplify the assembly of oligosaccharides.Differentiation of hydroxy groups on the carbohydrate is usually considered challenging as a result of the almost identical chemical environment. 1,2-trans diols are even more difficult to deal with compared to 1,2-cis diols. In my first project, I developed a method for regio- and stereo-selective OH carbene insertion together with my collaborator. Under very mild conditions, a series of 1,2-trans diols can be selectively functionalized. The regioselectivity originated from interactions between substrates and transition-metal catalysts, while the stereochemistry came from intramolecular proton delivery. The newly introduced moiety can work as a protection group, function group for the glycoconjugate mimic synthesis, or participate in the following glycosylation reactions and impact the anomeric selectivity. Inspired by the regio-selectivity of first projects, I developed another transition metal-catalyzed reaction, which could successfully epimerize one hydroxyl group in 1,2-trans diols, thus many rare sugars can be accessed easily starting from readily available common sugars. Compared to the traditional route, the method I developed can simplify the synthesis significantly and is more environmentally friendly. Synthesis of aminosugars through direct amination of 1,2-trans diols is also investigated. Bromodomain (BRD) is an evolutionarily conserved protein-protein interaction module that can recognize and bind acetylated lysine residues in histones and many other proteins. BRD4 protein, which is considered a transcriptional factor and epigenetic regulator, can bind to acetylated histone and recruit protein complexes to stabilize the binding of RNA polymerase II to histone. The dysregulation of BRD4 can cause cancer and other diseases such as immune and inflammatory diseases. Because of this, the BRD4 protein has been long considered an important therapeutic target. In the third project, I worked on the development of tissue-selective BRD4 degraders, aiming to provide a novel therapy for prostate cancer. By attaching tissue-selective ligands to BRD4 degraders, we successfully achieved selectivity among different cell lines, which proved our initial hypothesis. The tri-functional degraders will be tested in vivo in the future.