University of Missouri, St. Louis IRL @ UMSL Dissertations UMSL Graduate Works 1-14-2012 SUPERARMED GLYCOSYL DONORS IN CHEMICAL GLYCOSYLATION Hemali Deepthika Premathilake University of Missouri-St. Louis, [email protected] Follow this and additional works at: https://irl.umsl.edu/dissertation Part of the Chemistry Commons Recommended Citation Premathilake, Hemali Deepthika, "SUPERARMED GLYCOSYL DONORS IN CHEMICAL GLYCOSYLATION" (2012). Dissertations. 383. https://irl.umsl.edu/dissertation/383 This Dissertation is brought to you for free and open access by the UMSL Graduate Works at IRL @ UMSL. It has been accepted for inclusion in Dissertations by an authorized administrator of IRL @ UMSL. For more information, please contact [email protected]. SUPERARMED GLYCOSYL DONORS IN CHEMICAL GLYCOSYLATION By HEMALI D. PREMATHILAKE Master of Science (Chemistry), University of Missouri-St. Louis, May 2009 Bachelor of Science (Chemistry), University of Peradeniya, Sri Lanka, May 2005 A DISSERTATION Submitted to the Graduate School of the UNIVERSITY OF MISSOURI – ST. LOUIS in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY in CHEMISTRY November 11th 2011 Dissertation Committee Prof. Alexei V. Demchenko, Ph.D. (Chair) Prof. Christopher D. Spilling, Ph.D. Prof. Chung F. Wong, Ph.D. Prof. Cristina De Meo, Ph.D. (SIUE) Premathilake, Hemali D., UMSL, p.1 ABSTRACT Superarmed glycosyl donors in chemical glycosylation Hemali D. Premathilake Doctor of Philosophy University of Missouri – St. Louis Prof. Alexei V. Demchenko, Advisor Only recently has the tremendous biological significance and therapeutic potential of carbohydrates and conjugates thereof (glycoproteins, glycolipids, proteoglycans, etc.) begun to emerge. As the appreciation for the biological roles of carbohydrates a growing demand for efficient and scalable methods towards the synthesis of these challenging molecules has become even more imperative. This has led to the development of a variety of expeditious strategies for oligosaccharide assembly. Amongst these strategies, the so-called armed-disarmed strategy introduced by Fraser-Reid is of particular attractiveness as it allows for chemoselective oligosaccharide synthesis. Recently, the conformational changes as well as the strategic placement of common protecting groups have led to the discovery of new methods for “superarming” of glycosyl donors. This doctoral dissertation is dedicated to the exploration of new methods and strategies for efficient oligosaccharide assembly. The main focus of this work is centered on the detailed study of the superarmed glycosyl donors and broadening their application to the chemoselective oligosaccharide assembly. This study was supplemented by the Premathilake, Hemali D., UMSL, p.2 discovery of new leaving groups and application to the synthesis of biologically important oligosaccharides containing residues of sialic acid. ACKNOWLEDGEMENTS First and foremost I would like to express my gratitude to my Ph.D. Advisor, Dr. Alexei V. Demchenko for all of his support. After completing my undergraduate degree from University of Peradeniya, Sri Lanka, I wanted to pursue my Ph.D. at University of Missouri – St. Louis only because of my deep interest in carbohydrate chemistry. My dream came true by the acceptance for „GLYCOWORLD‟ and I really appreciate the great support and valuable guidance had from my advisor throughout my Ph.D. degree. I would also like to thank all the faculty members that have provided valuable chemistry knowledge along the way. Special thank goes to Prof. Cristina De Meo from Southern Illinois University, Edwardsville for sharing her knowledge in sialic acid chemistry. Also I would like to convey my gratitude to my undergraduate research advisor, Prof. Veranja Karunarathne for encouraging me to pursue my Ph.D. degree in good standards in United States, and without the instilled confidence and inspiration that I received from him, I would not have made as far academically, especially away from my family. Of course, any acknowledgement would not be complete without thanking my family and friends for their continued love and support. My dad and mom, Mr. and Mrs. Premathilake, have always had high expectations for me, and have encouraged me to Premathilake, Hemali D., UMSL, p.3 pursue my academic interests to the fullest extent, supporting me more than 100% of the way. My two younger brothers gave me all the moral support and love being the best brothers in the world. I would not achieve my goal without invaluable support, care and infinite love from my husband Mr. Chethiya Ranaweera, although I am thousand miles away from him for achieving my academic goals. Finally, I would like to thank all my friends in United States and Sri Lanka for their love and encouragement to achieve my goals. Premathilake, Hemali D., UMSL, p.4 LIST OF ABBREVIATIONS Å .............................................................................................................................Angstrom Ac ................................................................................................................................ Acetyl Ar………………………………………………………………………………………Aryl AgOTf ............................................................................... Silver trifluoromethanesulfonate Bn ............................................................................................................................... Benzyl br……………………………………………………………………………………..Broad Bz ............................................................................................................................. Benzoyl BF3(OEt)2 ...................................................................................... Boron trifluoride etherate Bu4NBr ................................................................................. Tetrabutylammonium bromide Cu(OTf)2 .................................................................... Copper(II) trifluoromethanesulfonate Cbz……………………………………………………………………..Benzyloxycarbonyl CDA……………………………………………………………..Cyclohexane 1,2-diacetal d................................................................................................................................. Doublet 1,2-DCE ..................................................................................................1,2-Dichloroethane DCM ...................................................................................................... Methylene chloride dd............................................................................................................ Doublet of doublets DMF .............................................................................................. N,N-Dimethylformamide DMTST .................................... Dimethyl(methylthio)sulfonium trifluoromethanesulfonate Et ................................................................................................................................... Ethyl Gal .......................................................................................................................... Galactose Glc ............................................................................................................................ Glucose Premathilake, Hemali D., UMSL, p.5 h................................................................................................................................. Hour(s) HR-EI MS ........................................... High Resolution Electron Ionization mass spectrum HR-FAB MS ............................. High Resolution Fast Atom Bombardment mass spectrum Hz .................................................................................................................................. Hertz IDCP………………………………………………….Iodonium(di-γ-collidine)perchlorate KOH ..................................................................................................... Potassium hydroxide LG…………………………………………………………………………...Leaving group m ............................................................................................................................. Multiplet min ......................................................................................................................... Minute(s) m/z ......................................................................................................... Mass to charge ratio Me .............................................................................................................................. Methyl MS .............................................................................................................. Molecular sieves NIS .......................................................................................................... N-Iodosuccinimide NMR ........................................................................................ Nuclear magnetic resonance PFBz…………………………………………………………………...Pentafluorobenzoyl Phth…………………………………………………………………………….Phthalimido Pic…………………………………………………………………………………Picolinyl Ph ............................................................................................................................... Phenyl ppm ............................................................................................................. Parts per million RRV………………………………………………………………Relative reactivity value Rf .................................................................................................................. Retention factor rt ..............................................................................................................