报告题目：Methylenecyclopropane Analogues of Nucleosides: Design, Synthesis and Antiviral Activity

报 告 人：周绍满博士（埃默里大学医学院高级研究助理）

报告时间：2011年11月16日（星期三）15:00

报告地点：独墅湖校区二期云轩楼1319会议室

报告摘要：

核苷类抗病毒药物是临床上用于治疗艾滋病、乙型肝炎、疱疹等病毒性疾病的主流药物，其作用靶点是RNA病毒的逆转录酶或DNA病毒的DNA聚合酶。它们模拟天然核苷的结构，竞争性作用于酶活性中心，嵌入正在合成的病毒DNA链中，终止DNA链的延长，从而抑制病毒复制。开环核苷类化合物作为核苷类抗病毒药物的重要一族，具有低毒、低耐受性和广谱抗病毒活性，对耐药菌株有强的杀伤作用，在抗病毒治疗领域占有重要地位，是近年研究的热点。报告将着重介绍新型开环核苷类化合物-亚甲基环丙烷核苷类抗病毒化合物的设计合成，以及具有这一特殊化学结构的不同核苷类似物与其抗病毒活性之间的关系。

报告人简介：

周绍满，博士，1994毕业于江西师范大学化学系；2000年毕业于中国科学院上海有机化学研究所,获得有机化学博士学位; 2000-2003美国韦恩州立大学(Wayne State University)，Karmanos 癌症研究所博士后；2003-2009 美国韦恩州立大学Karmanos癌症研究所研究助理；2009年3月至今埃默里大学（Emory University)医学院高级研究助理。主要从事抗病毒、抗肿瘤核苷类似物的设计合成及其构效关系的研究。由其主导设计合成的抗人类巨细胞病毒（HCMV）的专利化合物cyclopropavir(CPV)，已近完成前期临床研究，该国际专利已授权给一美国生物制药公司，将由该公司继续进行临床试验。在该研究领域中的许多研究成果，发表在Journal of Medicinal Chemistry，Antimicrobial Agents and Chemotherapy, Nucleosides, Nucleotides & Nucleic Acids，Tetrahedron 等核心期刊上（共11篇）。 

已授权国际专利一项：

Jiri Zemlicka, Shaoman Zhou, John C. Drach, Preparation of 2, 2-bis (hydroxymethyl)cyclopropylidenemethyl-purines and -pyrimidines as antiviral agents.    (WO2003104440), 美国专利号（US patent Number）： 7,393,855 B2；欧洲专利号：EP1490368 B1

代表性文章：

1.Shaoman Zhou, John C. Drach, Mark N. Prichard, Jiri Zemlicka, (Z)- and (E)-2-(1,2-Dihydroxyethyl)methylenecyclopropane Analogues of 2’-Deoxyadenosine and 2’-Deoxyguanosine. Syntheis of All Stereoisomers, Absolute Configuration and Antiviral Activity. J. Med. Chem. 2009, 52(10),  3397-3407.

2.Zhimeng Wu, Shaoman Zhou, Jiri Zemlicka, Stereoselective Approach to the Z-isomers of Methylenecycloproane Analogues of Nucleosides: A New Synthesis of Antiviral Synguanol. Nucleosides, Nucleotides & Nucleic Acids, 2009, 28(3), 165-174.

3. Shaoman Zhou, Mark N Prichard, Jiri Zemlicka, Methylene-2-ethynylcyclopropanes: synthesis and biological activity of (Z)- and (E)-9- { [2-ethynyl-2-(hydroxymethyl)cyclopropylidene]methyl} adenine and -guanine. Tetrahedron 2007, 63(38), 9406-9412.

4. Shaoman Zhou, Jiri Zemlicka, Earl R Kern, John C Drach, Fluoroanalogues of anti-cytomegalovirusagent cyclopropavir: synthesis and antiviral activity of  (E)-and (Z)-9- {[2,2-bis(hydroxymethyl)-3-fluorocyclopropylidene]methyl} –adenines and guanines. Nucleosides, Nucleotides & Nucleic Acids, 2007, 26(3), 23 1-243.

5. Shaoman Zhou, Jiri Zemlicka, Synthesis of 2,2,3-tris(hydroxymethyl)methylenecyclopropane analogues of nucleosides. Nucleosides, Nucleotides & Nucleic Acids, 2007, 26(4), 39 1-402.

6. Zhaohua Yan, Shaoman Zhou, Earl R Kern, Jiri Zemlicka, Synthesis of Methylenecyclopropane Analogues of Antivirial Nucleoside Phosphonates, Tetrahedron, 2006, 62(11), 2608-2615.

7. Shaoman Zhou, Earl R Kern, Elizabeth Gullen, Yung-Chi Cheng, John C Drach, Sadahiro Tamiya,Hiroaki Mitsuya, Jiri Zemlicka, 9- { [3-Fluoro-2-(hydroxymethyl)cyclopropylidene]methyl} adenines and -guanines. Synthesis and antiviral activity of all stereoisomers. J. Med. Chem , 2006, 49(20), 6120-6128.

8. Shaoman zhou, Jiri Zemlicka, A New Alkylation-Elimination Method for Synthesis of Antiviral 4’-Fluoromethylenecyclopropane Analogues of Nucleosides, Tetrahedron, 2005, 61, 7112-7116.

9. Earl R. Kern, Nicole L. Kushner, Caroll B. Hartline, Stephanie L. Williams-Aziz, Emma A. Harden, Shaoman Zhou, Jiri Zemlicka, and Mark N. Prichard, In Vitro Activity and Mechanism of Action of Methylenecyclopropane Analogs of Nucleosides against Herpesvirus Replication, Antimicrobial Agents and Chemotherapy, 2005, 49 (3), 1039-1045.

10.Shaoman Zhou, Earl R Kern, Elizabeth Gullen, Yung-Chi Cheng, John C Drach, Shintaro Matsumi, Hiroaki Mitsuya, Jiri Zemlicka, (Z)- and (E)-[2-Fluoro-2-(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines, a New Class of Methylenecyclopropane Analogues of Nucleosides: Synthesis and Antiviral Activity, J. Med. Chem , 2004, 47(27); 6964-6972.

11. Shaoman Zhou, Julie M Breitenbach, Katherine Z Borysko, John C Drach, Earl R Kern, Elizabeth Gullen,, Yung-Chi Cheng, , Jiri Zemlicka, Synthesis and Antiviral Activity of (Z)- and (E)-2,2-[Bis(hydroxymethyl)cyclopropylidene]methylpurines  and-pyrimidines: Second-Generation Methylenecyclopropane Analogues of Nucleosides, J. Med. Chem , 2004, 47(3), 566-575.

12.Shaoman Zhou, Min-Zhi Deng, Li-Jun Xia, Ming-Hua Tang Efficient Suzuki-Type Cross-Coupling of Enantiomerically Pure Cyclopropylboronic Acids , Angew. Chem.Int.Ed.Engl. 1998,37,2845-2847.