报告时间:2019年10月15日(星期二),09:30-11:30
报告地点:闵行校区必赢线路检测3003no1 树华多功能厅
联系人:林双君
报告人:Hung-wen Liu (Division of Chemical Biology & Medicinal Chemistry, College of Pharmacy, and Department of Chemistry, University of Texas at Austin)
Abstract:
Scopolamine is a tropane alkaloid found in the Solanaceae family of plants. It has antagonistic activity against muscarinic acetylcholine receptors. The construction of the epoxide ring in scopolamine is of great interest, because it is formed by oxidation of two unactivated methylene groups of hyoscyamine, the precursor to scopolamine. The epoxidation is catalyzed by hyoscyamine 6β-hydroxylase (H6H) which is a mononuclear non-heme iron- and α-ketoglutarate-dependent dioxygenase. The overall transformation involves a two-step oxidation of hyoscyamine: hydroxylation of an aliphatic carbon followed by dehydrogenation of the resulting secondary alcohol. A high-valent iron(IV)-oxo species generated via activation of molecular oxygen is believed to be involved in both steps. However, the detailed mechanism regarding how H6H controls these two sequential oxidation reactions remains unclear. To address these mechanistic questions, experiments were carried to gain more insights into the catalysis of H6H. The results of these experiments will be presented and discussed.
报告人简介:
刘鸿文教授,1981年在哥伦比亚大学获博士学位,师从Koji Nakanishi教授;1981-1984在麻省理工大学Christopher T. Walsh教授实验室从事博士后研究。1984-2000年任职于明尼苏达大学化学系,获杰出教授称号。2001年至今任职于德克萨斯大学奥斯汀分校药学院及化学和生物化学系,George H. Hitchings药物设计讲座教授。现为美国科学促进会和日本科学促进会Fellow,美国微生物科学院Fellow,美国化学学会Fellow。刘鸿文教授实验室聚焦在化学和生物学的交叉领域,重点关注生物催化机制与药物设计、代谢途径工程、生物催化剂应用等,长期致力于利用有机化学和生物催化工具研究抗生素的合成机理,取得了令人瞩目的研究成果,并因此先后获得过多项学术奖励,如Camille & Henry Dreyfus基金会杰出化学新进教授奖、美国癌症学会青年教授奖、Eli Lilly生命科学青年学者奖、美国卫生福利部研究发展奖、美国化学会糖化学部Horace S. Isbell奖(1993)、美国国家基础医学研究院杰出研究奖、美国化学会有机化学部Nakanishi奖(2007)、美国化学会生物化学部Repligen奖(2008),生物化学研究A. I. Scott杰出勋章(2011),美国化学会Arthur C. Cope Late Career Scholars Award(2014),美国化学会糖化学部Claude S. Hudson Award (2019)等二十多项。刘鸿文教授担任ACS期刊Organic Letters的副主编,及多种生物有机化学和化学学术期刊的编委会成员,至今发表了280篇论文,其中超过1/3发表在Nature、Science、PNAS、J. Am. Chem. Soc.和Angew. Chem. Int. Ed.等期刊上。