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题目：Stereoselective Synthesis and Development of carbocyclic Nucleoside Analogues as potential new antiviral Agents
报告人：Prof. Dr. Chris Meier, University of Hamburg
时间：2019年5月28日  星期二 10:00--11:00
地点：购彩大厅 A楼528会议室 
邀请人： 张勇健研究员


Abstract：
Structural analogues of the naturally occurring nucleosides, which are the building blocks for DNA and RNA, are used as antiviral agents in chemotherapy since long time. In carbocyclic nucleosides the furanose ring oxygen atom has been replaced by a carbon atom. Carbocyclic nucleosides have been isolated from natural sources and have been used as antiviral agents as well, e.g. in anti-HIV chemotherapy the compound abacavir and against hepatitis B infections the carbocyclic entecavir. Carbocyclic nucleosides have several advantages over the furanose containing nucleoside analogues, e.g. metabolic stability. However there chemical synthesis is much more demanding as compared to the furanose ring containing analogues. In the lecture various synthetic route developed by my group towards this class of compounds will be described. This includes stereoselective and regioselective reaction such as hydroborations, eliminations, ligand-controlled catalyzed hydroxylations and enzyme-catalyzed kinetic resolutions to gain access to appropriate chiral precursors. Nucleosides were generally built by the Mitsunobu reaction. Thus, we were able to develop reliable access toward D- or L- 2’-deoxy, ribo-, 2’,3’-dideoxy- and 2’,3’-dideoxy,2’,3’-didehydronucleoside analogues. In the second part, these synthetic approaches were used to prepare carbocyclic analogues of abacavir and carbovir. To these compounds our nucleoside triphosphate delivery technology has been applied to get to potentially highly active antiviral agents.
 
简介：
 Education Background：
1982 – 1987 Academic training in Chemistry, Philipps-University of Marburg and Diploma thesis
1987 – 1989  Ph.D. thesis (Organic Chemistry), Prof. Dr. Gernot Boche, University of Marburg/Lahn
1990 – 1991 Post-doctoral Fellow in the group of Prof. Igolen, Organic Chemistry, Pasteur-Institute/Paris, France
Working Experiences：
1991 – 1997 Assistant Professor, university of Frankfurt/Main, Germany
1997 – 1999 Associate Professor, University of Würzburg, Germany
since 1999 Full Professor for Organic Chemistry - C4/W3, University of Hamburg, Germany
Research Interests：
Nucleoside/Nucleotide Chemistry
Pronucleotide Development
Antisense-Oligonucleotide Chemistry
Stereoselective Synthesis of carbocyclic Nucleoside Analogues
Molecular Basis of the induction of chemical carcinogenesis
Synthesis of Sugar-Nucleotide-Pyrophosphates
Solid-Support based Organic Synthesis