主讲课程
生物工程专业英语、高等有机化学、科技英语论文写作、生物有机化学、环境工程概论、药物合成反应。
个人简介
教授，博导，999全讯白菜网药物所副所长，绿色制药工艺及新药研发。2015年“江苏省六大人才高峰”生物医药领军人才。在国际化学生物期刊上发表论文八十多篇，其中SCI 70多篇和EI 8篇，SCI统计总被引用次数超过500次。获中国发明专利授权11项（转让二项）。工作中提出Chemology（化学逻辑学）和创新哲学概念，运用化学逻辑（Chemological Rule）和创新哲学（Creation Philosophy）探究、阐释、构建大（生物）小（非生物）分子间的分子关系学(Molecular Relationship)。担任国家科技奖评审专家，国家基金委自然基金评审专家，教育部学位论文评审专家，教育部科技部组织部等人才计划评审专家，全国多省市学术、学科与技术项目以及科技奖评审专家，江苏省化工产业安全环保整治提升攻坚行动“一企一策”专项检查组组长，省环评技术评审专家。
教育背景：
1982-1986，南京师范大学，理学学士；
1986-1989，中国科学院大连化学物理研究所，理学硕士；
1996-1999，中国科学院上海有机化学研究所，理学博士；
1999-2000，美国Texas A&M University大学，博士后；
2000-2002，美国 University of North Carolina at Chapel Hill大学，博士后。
工作经历：
1989-1996，中国科学院大连化学物理研究所，助理研究员；
2002-2002， 上海药明康德PharmaTech新药研发公司，高级研究员，项目负责人Project Manager, 科研组长Group Header, 实验室副主任；
2002-2003，瑞士罗氏Roche制药(巴塞里亚Basilea药物)中国研发中心，科研处长 Division Header；
2003-2005，美国礼来Eli Lilly制药公司上海（开拓者化学)研发中心，总监Director；
2005 - 今， 全讯白菜策略，研究员(Professor)；
2019-2020，江苏省淮安市洪泽经济开发区管委会副主任。
科研项目：
在药明康德新药研发公司、罗氏制药江苏原创药物研发中心、美国礼来制药上海公司担任技术总监，完成新药研发项目多项。2005年到全讯白菜策略工作以来，先后主持完成了国家自然科学基金专项项目一项、面上项目一项、中国科学院重点实验室项目三项、国家新药重大创制项目子课题“双氢青蒿素二倍体衍生物高效抗疟创新药物的研究--青蒿素衍生物的合成与放大工艺研究”、国家863课题子项目三项（手性药物与绿色化工）、国际合作项目二项、江苏省生物技术创新项目子课题一项、江苏省六大人才高峰生物医药领域项目一项、安徽省长三角联合科技攻关项目、999全讯白菜网校立项目三项、企业合作项目数十项。目前研究中的课题有江苏省先进生物制造协同创新项目、抗感染新药研发、抗细菌生物被膜活性的YycG组氨酸激酶小分子抑制剂的设计与合成、新一代绿色催化反应与制药新技术研发、单质硫/硒介导的噻/硒唑化合物构建及应用于药物分子合成、药物生产研发公司合作项目多项。并与制药化工类企业结成多个协同研发战略联盟。
研究成果包括：
l 抗细菌生物被膜活性的YycG组氨酸激酶小分子新药的发现；
l 绿色有机合成新催化反应体系建立及其应用于药物分子合成；
l 首次提出特制醇腈酶颗粒在单一有机相溶媒中催化合成手性氰醇的新方法及连续流动酶合成装置，以及新型醇腈酶的发现，首次完成国际上未能成功的手性杂环氰醇和手性氟取代氰醇的合成，得到该领域国际专家的关注引用和评述(被Chem. Rev. , Curr. Opin. Chem. Biol., Curr. Opin. Biotech., Curr. Org. Chem., Top. Curr. Chem., Tetra. Asymm.等作为该领域重要的研究进展评述，被Highlight 和引述数百次，Methods in Organic Synthesis两次收录)；
l 生物催化合成（S）-丁呋洛尔等手性药物；
l 完成抗癌新药秋水仙碱和鬼臼毒素系列衍生物的发明；
l 醇类选择性分子氧氧化新催化剂的发明；半乳糖氧化酶模拟反应的机理研究，用原位紫外和ESR技术捕捉到催化剂活性价态；
l 国际上第一个将杂多酸催化剂用于饱和烃的羟化反应并且应用原位红外技术捕捉到催化剂活性物种；
在PharmaTech, Basilea和Eli Lilly公司负责完成研究项目约五十个，设计合成了一万多个药物活性分子用于新药的筛选。
代表性成果
作为通讯作者或第一作者的代表性SCI论文：
一、药物化学代表性论文：
1. Xuecheng Chen , Yanpeng Xiong , Yue Luo , Yalan Peng, Zhong Chen , Zhijian Yu，Shiqing Han, Derivatization of Dihydropyrrolidone-Thiadiazole Heterocyclic Compounds and Evaluation of Its Antibacteria and Anti-Biofilm Activities, Synthesis, 2023, DOI: 10.1055/a-2023-0028.
2. Xuecheng Chen, Liang Hu,Yanpeng Xiong, Yurong Zhang, Yue Luo, Yalan Peng, Zhong Chen, Jie Zhang, Zhijian Yu, Shiqing Han, Development of 2-Alkyl-5-((phenylsulfonyl)oxy)-1H-indole-3-carboxylate Derivatives as Potential Anti-Biofilm Agents, ChemistrySelect, 2023, 8 (5), e202204226.
3. Zhang Shiju, Li Xiaotong, Wang Yan, Zheng Yucong, Shiqing Han, Yu Huilei, Huang Shahua. Formal Synthesis of Gram-Negative Antibiotic Negamycin, Chinese Journal of Organic Chemistry, 2020, 40(2): 521-527.
4. Zhihui Lv, Dan Zhao, Jun Chang, Huayong Liu, Xiaofei Wang, Jinxin Zheng, Renzheng Huang, Zhiwei Lin, Yongpeng Shang, Lina Ye, Yang Wu, Shiqing Han and Di Qu , Anti-bacterial and Anti-biofilm Evaluation of Thiazolopyrimidinone Derivatives Targeting the Histidine Kinase YycG Protein of Staphylococcus epidermidis, Frontiers in Microbiology, 2017, 8, 1-10.
5. Huayong Liu, Yanfeng Zhao, Dan Zhao, Ting Gong, Youcong Wu, Haiyan Han, Tao Xu, Andreas Peschel, Shiqing Han, and Di Qu, Antibacterial and anti-biofilm activities of thiazolidione derivatives against clinical staphylococcus strains, Emerging Microbes and Infections, 2015, 4, e1; doi:10.1038/emi.2015.1
6. Huayong Liu, Dan Zhao, Jun Chang, Liang Yan, Fuju Zhao, Youcong Wu, Tao Xu, Ting Gong, Li Chen, Nianan He, Yang Wu, Shiqing Han, Di Qu, Efficacy of novel antibacterial compounds targeting histidine kinase YycG protein, Appl Microbiol Biotechnol, 2014, 98, 6003-6013.
7. Dan Zhao, Chen Chen, Huayong Liu, Likang Zheng, Yao Tong, Di Qu, Shiqing Han, Biological evaluation of halogenated thiazolo[3,2-a]pyrimidin- 3-one carboxylic acid derivatives targeting the YycG histidine kinase, European Journal of Medicinal Chemistry, 2014, 87, 500-507.
8. Dan Zhao, Likang Zheng, Huayong Liu, Guozhen He, Di Qu, Shiqing Han, Synthesis of novel 4-thiazolidione derivatives as antibacterial agents against drug-resistant Staphylococcus epidermidis, Medicinal Chemistry Research, 2013, 22, 3743–3750.
9. Jie Zhang, Likang Zheng, Dan Zhao, Huayong Liu, Di Qu, Shiqing Han, Synthesis and Biological Evaluation of Halogenated 2-Arylimino-3 -arythia- zolidine-4-ones Containing Benzoic Acid Fragments as Antibacterial Agents, Letters in Drug Design & Discovery, 2013, 10 (10), 928-934.
10. Renzheng Huang, Likang Zheng, Huayong Liu, Bin Pan, Jian Hu, Tao Zhu, Wei Wang, Danbin Jiang, Yang Wu, Youcong Wu, Shiqing Han, and Di Qu, Thiazolidione derivatives targeting the histidine kinase YycG are effective against both planktonic and biofilm-associated Staphylococcus epidermidis, Acta Pharmacologica Sinica, 2012, 33, 418-425.
11. Bin Pan, Renzheng Huang, Likang Zheng, Chen Chen, Shiqing Han, Di Qu, Mingli Zhu, Ping Wei, Thiazolidione derivatives as novel antibiofilm agents: design, synthesis, biological evaluation, and structure-activity relationships, European Journal of Medicinal Chemistry, 2011, 46(3), 819-824.
12. Bin Pan, Ren-Zheng Huang, Shiqing Han, Di Qu, Ming-Li Zhu, Ping Wei and Han-Jie Ying, Design, synthesis, and antibiofilm activity of 2-arylimino-3-aryl- thiazolidine-4-ones, Bioorganic & Medicinal Chemistry Letters, 2010, 20(8), 2461-2464.
13. Shiqing Han, Zhiyan Xiao, Kenneth F. Bastow and Kuo-Hsiung Lee, Antitumor Agents Part 230: C4’-esters of GL-331 as cytotoxic agents and DNA topoisomerase II inhabitors, Bioorganic & Medicinal Chemistry Letters, 2004, 14(11), 2979-2982.
14. Zhiyan Xiao, Shiqing Han, Kenneth F. Bastow and Kuo-Hsiung Lee, Antitumor Agents Part 232: Synthesis of cyclosulfite podophyllotoxin analogues as novel prototype antitumor agents, Bioorganic & Medicinal Chemistry Letters, 2004, 14(6), 1581-1584.
15. Shiqing Han, Hamel-E, Bastow-KF, Mcphail-AT, Brossi-A, Lee-KH, Antitumor Agents Part 215:Antitubulin Effects of Cytotoxic B-Ring Modified Allocolchicinoids, Bioorganic & Medicinal Chemistry Letters, 2002, 12(20), 2851-2853.
二、绿色化学与制药新技术代表性论文：
16. Jun Zhang, Liang Hu, Yafei Liu, Yurong Zhang, Xuecheng Chen, Yue Luo, Yalan Peng, Shiqing Han, Bin Pan, Elemental Sulfur-Promoted Benzoxazole/Benzothiazole Formation Using a C═C Double Bond as a One-Carbon Donator. The Journal of Organic Chemistry, 2021, 86, 21, 14485–14492.
17. 张俊，刘雅菲，张育榕，呼亮，韩世清，2-取代苯并噻唑化合物的合成进展，有机化学，2021, 41（3）,1053-1071.
18. Yafei Liu , Yurong Zhang , Jun Zhang , Liang Hu , Shiqing Han, A copper-catalyzed approach for the synthesis of asymmetrical disubstituted 1,2,4-thiadiazoles via elemental sulfur-mediated decarboxylative redox cyclization. Tetrahedron Letters, 2021, 65, 152744.
19. Yurong Zhang , Yafei Liu , Jun Zhang , Ren Gu , Shiqing Han, An alternatively metal-free synthesis of 1,3,5-triazines or 1,2,4-thiadiazoles from benzyl chlorides and benzylamines mediated by elemental sulfur. Tetrahedron Letters, 2019, 60 (49), 151289.
20. Ren Gu, Xin Wang, Zhao Yang, Shiqing Han, Se-mediated one-pot synthesis of 2-substituted benzoselenazole derivatives from 2-iodoanilines and arylacetic acids/arylmethyl chlorides. Tetrahedron Letters, 2018, 59 (29), 2835-2838.
21. Xin Wang, Xiaotong Li, Renhe Hua, Zhao Yang, Ren Gu, Sai Ding, Pengyi Li, Shiqing Han, Elemental Sulfur-Mediated Decarboxylative Redox Cyclization Reaction: Copper-Catalyzed Synthesis of 2-Substituted Benzothiazoles, Synlett, 2018, 29, 219-224.
22. Xin Wang, Dazhuang Miao, Xiaotong Li, Renhe Hua, Zhao Yang, Ren Gu, Shiqing Han, Elemental Sulfur Mediated Cyclization via Redox Strategy: Synthesis of Benzothiazoles from o-Chloronitrobenzenes and Benzyl chlorides, Tetrahedron, 2017, 73, 5194-5199.
23. Zhao Yang, Renhe Hu, Xiaotong Li, Xin Wang, Ren Gu, Shiqing Han, One-pot Copper-Catalyzed Synthesis of 2-Substituted Benzothiazoles from 2-Iodoanilines, Benzyl Chlorides and Elemental Sulfur, Tetrahedron Letters, 2017, 58, 2366～2369.
24. Haifeng Gan, Dazhuang Miao, Qiang Pan, Renhe Hu, Xiaotong Li, and Shiqing Han, S8-Mediated Cyclization of 2-Amino Phenols/Thiophenols with Arylmethyl Chloride: Approach to Benzoxazoles and Benzothiaz, Chemistry – An Asian Journal, 2016, 11, 1770-1774.
25. Xiaotong Li, Qiang Pan, Renhe Hu, Xin Wang, Zhao Yang, and Shiqing Han, S8-Mediated One-Pot Synthesis of Thioamides from Benzyl Chlorides and Amines, Asian Journal of Organic Chemistry, 2016, 5, 1353-1358.
26. Xiaotong Li, Renhe Hu, Yao Tong, Qiang Pan, Dazhuang Miao, Shiqing Han, An Efficient Route for the Synthesis of Benzimidazoles via a Hydrogen-Transfer Strategy between o-nitroanilines and Alcohols, Tetrahedron Letters, 2016, 57, 4645-4649.
27. Renhe Hu, Xiaotong Li, Yao Tong, Dazhuang Miao, Qiang Pan, Zengqiang Jiang, Haifeng Gan, Shiqing Han, Catalyst-Free Synthesis of 2-Arylbenzothiazoles in an Air/DMSO Oxidant System, Synlett, 2016, 27, 1387-1390.
28. Qiang Pan, Chun-Yang He, Shiqing Han, Xingang Zhang, Palladium-Catalyzed Direct Thienylation of Monobromide-Substituted Difluorinated Benzothiadiazoles for Organic Photovoltaics, Synlett, 2015, 26, 2175-2179.
29. Zeng-qiang Jiang, Da-zhuang Miao, Yao Tong, Qiang Pan, Xiao-tong Li, Ren-he Hu, Shiqing Han, One-Pot Base-Mediated Synthesis of Functionalized Aza-Fused Polycyclic Quinoline Derivatives, Synthesis, 2015, 47, 1913-1921.
30. Dazhuang Miao, Xuesong Shi, Guozhen He, Yao Tong, Zengqiang Jiang, Shiqing Han, One-pot synthesis of 2-arylbenzoxazole derivatives via Cu(I) catalyzed C-N/C-O coupling of N-(2-chloro-phenyl)-2-halobenzamides and primary amines, Tetrahedron, 2015, 71, 431-435.
31. Yao Tong, Qiang Pan, Zengqiang Jiang, Dazhuang Miao, Xuesong Shi, Shiqing Han, A simple approach to benzothiazoles from 2-chloronitrobenzene, elemental sulfur, and aliphatic amine under solvent-free and catalyst-free conditions, Tetrahedron Letters, 2014, 55, 5499-5503.
32. Zengqiang Jiang, Jie Zhang, Yao Tong, Xuesong Shi, Dazhuang Miao, Shiqing Han, One-Pot Synthesis of Pyrrolo[1,2-a]quinoxaline Derivatives through Copper-Catalyzed Cascade Reactions, Chin. J. Org. Chem. 2014, 34, 1845-1850.
33. Guozhen He, Yuan Huang, Yao Tong, Jie Zhang, Dan Zhao, Shuangli Zhou, Shiqing Han,Substrate-Promoted Ligand-Free CuI Catalyzed S-Arylation of 2-Mercapto- benzothiazoles with Aryl Iodides in Water, Tetrahedron Letters, 2013, 54, 5318–5321.
34. Ming Jin, Dan Zhao, Guozhen He, Yao Tong, Shiqing Han, Substrate-promoted copper-catalyzed N-arylation of amino alcohols with aryl iodides in water, Chinese Journal of Catalysis, 2013, 34 (9), 1651-1655.
35. Yuan Huang, Wei Chen, Dan Zhao, Chen Chen, Huiqing Yin, Likang Zheng, Ming Jin, Shiqing Han, Copper(I)-Catalyzed Intramolecular Direct C-Arylation of Azoles with Aryl Bromides, Chinese Journal of Chemistry, 2013, 31, 1007-1010.
36. Jie Zhang, Zengqiang Jiang, Dan Zhao, Guozhen He, Shuangli Zhou, Shiqing Han,Transition-Metal-Free TEMPO Catalyzed Aerobic Oxidation of Alcohols to Carbonyls Using an Efficient Br2 Equivalent under Mild Conditions, Chinese Journal of Chemistry, 2013, 31, 794-798.
37. Huiqing Yin, Ming Jin, Wei Chen, Chen Chen, Likang Zheng, Ping Wei and Shiqing Han, Solvent-free Copper-catalyzed N-Arylation of Amino Alcohols and Diamines with Aryl Halides, Tetrahedron Lett. 2012, 53(10), 1265-1270.
38. Jingxian Zhang, Huiqing Yin, Shiqing Han, Copper-Catalyzed N-Arylations of Nitrogen-Containing Heterocycles in Water, Chin. J. Org. Chem., 2012, 32(8), 1429-1433.
39. Jingxian Zhang, Rui Zhang, Bin Tao, Shiqing Han, George Li, Preparation of novel pyridazine-4-boronic acid pinacol esters and imidazole-4-boronic acid pinacol esters through palladium-catalyzed cross-coupling reactions, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2012, 244, 625-ORGN.
40. Xinyu Li, Cheng Li, Wenjing Zhang, Xiang Lu, Shiqing Han, and Ran Hong, Highly Stereoselective 7-Endo-Trig/Ring Contraction Cascade To Construct Pyrrolo[1,2-a] quinoline Derivatives, Org. Lett. 2010, 12(8), 1696-1699.
三、生物酶催化手性合成代表性论文：
41. Shiqing Han, Chaosen Chu, Synthesis of Chiral Drugs by (R)-Oxynitrilase-Catalyzed Transformation, J. Biotechnology, 2008, 136S, 396- 397.
42. Shiqing Han, Pingkai Ouyang, Ping Wei and Yi Hu, Enzymatic Synthesis of (R)-Cyanohydrins by Novel (R)-Oxynitrilase from Vicia Sativa L., Biotechnology Letters, 2006, 28(23), 1909-1912.
43. 褚朝森，韩世清，韦萍，新手性试剂(1R, 2S)-2-氨基醇的合成，化学试剂，2009，31(2),125-127.
44. 褚朝森，韩世清，韦萍，(R)-醇腈酶催化法合成(R)-(-)-1-(2-萘基)-2-N-甲基氨基乙醇，高校化学工程学报, 2008, (6),999-1003.
45. 韩世清，褚朝森，韦萍，（R）-醇腈酶催化合成手性药物光学活性（S）-丁呋洛尔, 精细化工，2008，25(11),1106-1109。
46. 褚朝森，韩世清，韦萍，醇腈酶催化合成手性氰醇的研究进展，化工生产与技术，2007，14（6），55-59。
47. Chen-PR, Gu-JX, Wei-ZL, Shiqing Han, Li-ZY, Lin-GQ, Asymmetric Synthesis aided by Biocatalysts, Chin. J. Chem. 2003, 21(8), 983-993.
48. Chen-PR Shiqing Han Lin-GQ Li-ZY, A Practical High Through-Put Continuous Process for the Synthesis of Chiral Cyanohydrins, Journal Of Organic Chemistry, 2002, 67(23), 8251-8253.
49. Shi-Qing Han, Peiran Chen, Guo-Qiang Lin, Hao Huang and Zu-Yi Li, (R)-Oxynitrilase-catalyzed Hydrocyanation: the First Synthesis of Optically Active Fluorinated Mandelonitriles, Tetrahedron Asymmetry, 2001, 12, 843.
50. Peiran Chen, Shi-Qing Han, Guo-Qiang Lin, Hao Huang and Zu-Yi Li, A Study of Asymmetric Hydrocyanation of Heteroaryl Carboxaldehydes catalyzed by (R)-Oxynitrilase under Micro-aqueous Conditions, Tetrahedron Asymmetry, 2001, 12(23), 3273-3279.
51. Guo-Qiang Lin, Shi-Qing Han and Zu-Yi Li, Enzymatic Synthesis of (R)-Cyanohydrins by Three (R)-Oxynitrilase Sources in Micro-aqueous Organic Medium, Tetrahedron, 1999, 55, 3531.
52. Shi-Qing Han, Guo-Qiang Lin and Zu-Yi Li, Synthesis of (R)-Cyanohydrins by Crude (R)-Oxynitrilase-catalyzed Reactions in Micro-aqueous Medium, Tetrahedron: Asymmetry, 1998, 9(11), 1835.
四、早期科研代表性论文：
53. 韩世清，杨振云，郑禄彬，富勒烯C60/C70的制备化学，化学通报，1996, (5), 11。
54. 韩世清，曹国英，奚祖威，常温下环己烷的液相羟基化反应，催化学报，1995, 16(6), 514。
55. 韩世清，曹国英，奚祖威，钼钒磷杂多化合物过氧化氢体系催化饱和烃的羟化反应，催化学报，1995, 16(5), 392。
56. 韩世清，奚祖威，黄家壁，双齿铜(Ⅱ)络合物催化作用下分子氧对醇类的选择性氧化，分子催化，1991, 5(4), 316。
57. 韩世清，奚祖威，黄家壁，醇类催化氧化反应的机理研究—半乳糖氧化酶化学模拟体系，分子催化，1991, 5(3), 248。
申请（授权）专利：
1. 韩世清，陈学成，呼亮，余治健，陈重，熊焱鹏，罗悦，彭雅兰. 一种含1,3,4-噻二唑的3-羟基-吡咯-2-酮类化合物及其合成方法和应用.中国发明专利,CN114957238A.
2. 韩世清，罗悦，呼亮，余治健，陈重，熊焱鹏，陈学成，彭雅兰. 卤素取代的1,2,3,5-四取代-1H-吲哚类化合物及其合成方法和应用. 中国发明专利, 202210551139X.
3. 韩世清，张俊，刘雅菲，张育榕，呼亮．一锅法合成2-取代苯并噻唑的方法．中国发明专利；CN 110845439 A
4. 韩世清，顾忍，张育榕，等．一种合成1，3，5-三嗪衍生物的方法．中国发明专利；201910410732.0（已授权）
5. 韩世清，刘雅菲，张育榕，等．一种合成1,2,4-噻二唑衍生物的方法．中国发明专利；201911170692.3．
6. 韩世清;童耀;潘强;蒋增强;苗大状, 一种合成2-取代苯并噻唑衍生物的方法，中国发明专利, 201410205413.3(已授权)。
7. 韩世清;苗大状;史雪松;蒋增强;童耀;黄媛;潘强，一锅法合成二苯二氮卓杂环衍生物的方法，中国发明专利, 201410206756.1。
8. 韩世清;蒋增强;童耀;苗大状;潘强;史雪松;黄媛，一种5-甲腈-吡咯[1,2-a]喹啉衍生物的合成方法，中国发明专利, 201410205415.2。
9. 韩世清;蒋增强;张杰;童耀;何国珍;周双利;赵丹，一种合成5-甲腈-吡咯[1,2-a]喹啉衍生物的方法，中国发明专利, 201410205394.4(已授权)。
10. 韩世清;蒋增强;张杰;童耀;何国珍;周双利;赵丹，一种合成吡咯[1,2-a]喹喔啉衍生物的方法,中国发明专利, 201310239066.1。
11. 韩世清;蒋增强;张杰;童耀;何国珍;周双利;赵丹，吡咯[1,2-a]喹喔啉衍生物的合成方法，中国发明专利, 201310238303.2(已授权)。
12. 韩世清;方淑莹；何国珍，制备亚磺酰基-1-氢-苯并咪唑衍生物的方法,中国发明专利, 201310669517.5(已授权)。
13. 韩世清;何国珍；张杰；赵丹；周双利，一种小分子cathepsin D 抑制剂的制备方法，中国发明专利, 201310130670.0(已授权)。
14. 韩世清;张杰；蒋增强；赵丹；何国珍；周双利，一种选择性催化分子氧氧化水杨醇制备水杨醛的方法，中国发明专利, 201210570307.6(已授权)。
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