陳應春[四川大學華西藥學院教授]

陳應春,男,四川大學華西藥學院教授。

人物經歷

1990~1994 天津南開大學化學系有機化學專業 本科。

1994~1997 華西醫科大學藥學院藥物化學專業 碩士研究生。

1998~2001 中科院成都有機化學研究所有機化學專業 博士研究生。

2001~2002 中科院成都有機化學研究所 博士後研究。

2002~2003 香港大學化學系 博士後研究。

2003~ 四川大學華西藥學院 教授、博士生導師。

現為第三軍醫大學藥學院藥物化學專業 教授。

研究方向

1. 手性有機小分子催化的不對稱合成研究及手性藥物合成。

2. (手性)卡賓催化的新反應研究。

3. 新型可回收(手性)催化劑的設計、合成及催化反應研究。

4. 新型藥物設計與合成。

主要從事新型手性有機催化劑的設計、合成及不對稱催化反應研究以及生理活性物質的設計、合成等方面的工作。

主要貢獻

重點在手性有機小分子催化的不對稱合成領域開展研究並獲得了系列成果:1)在基於氫鍵活化的手性硫脲等催化劑的設計及其促進的不對稱反應進行了多方面研究,建立了結構、功能多樣的基於氫鍵活化的有機催化劑庫,在多種不對稱催化反應中實現了好的立體控制,發展了多種重要手性中間體、特別是非天然胺基酸的不對稱合成方法。2)在手性伯、仲胺通過烯胺、二烯胺、三烯胺及亞胺鹽機制催化飽和或不飽和醛和酮以及叔胺、叔膦等作為Lewis base催化Morita-Baylis-Hillman產物碳酸酯的不對稱轉化反應等領域開展了系統的研究,在催化劑、催化機制及新型催化反應的設計等多方面進行了積極探索。課題組首先採用從天然金雞納鹼衍生的手性伯胺在催化不飽和酮的不對稱反應方面取得好結果,為開拓不飽和酮的新型不對稱反應以及發展新的手性胺催化體系進行了創造性探索;首次發展了手性胺催化2,4-二烯醛和2,4-二烯酮的三烯胺催化機制,建立了不飽和羰基化合物的多類遠端不對稱反應新途徑;建立了數十種多官能團、多手性中心化合物的合成新方法,建立數千個新型化合物庫;通過計算機輔助和細胞篩選實驗,發現多類新穎的抗腫瘤、抗肺纖維化等新結構物質,為進一步發現和設計新型生理活性手性化合物奠定堅實基礎。

作為通訊作者已在Nat. Chem. 、Chem. Soc. Rev.、Acc. Chem. Res.、Angew. Chem. Int. Ed.、J. Am. Chem. Soc. 等國內外學術期刊上發表SCI論文110餘篇,總他引超過4800次。參與《Cinchona Alkaloids in Synthesis & Catalysis: Ligands, Immobilization and Organocatalysis》、《Asymmetric Organocatalysis》、《Organocatalytic Ring-Forming Reactions》等英文專著章節的撰寫工作。完成了包括國家Ⅰ類抗癌新藥Cambretastatin A-4 水溶性前藥、國家Ⅰ類抗膿毒症新藥KB甲烷磺酸鹽等藥物的合成研究(均進入臨床研究)。

課題及成果

1. 基於硫脲活化的雙功能有機催化劑的合成及不對稱催化反應研究。(國家自然科學基金,2006-2008)。

2. 新型水溶性紫杉醇前藥的研究。(教育部霍英東青年教師基金,2006-2008)。

3. 新世紀優秀人才支持計畫。(教育部,2006-2008)。

4. 四川省青年科技基金。(四川省,2007-2009)。

5. 手性伯胺有機催化劑的設計、合成及不對稱催化反應研究。(國家自然科學基金,2008-2010)。

代表性論著

1. Wei Chen,Wei Du,Yong-Zheng Duan,Yong Wu,Sheng-Yong Yang,Ying-Chun Chen,* “Enantioselective 1,3-dipolar cycloaddition of cyclic enones catalyzed by multifunctional primary amine: beneficial effects of hydrogen bonding”,Angew. Chem.,Int. Ed. 2007,46,7667.

2. Tian-Yu Liu,Hai-Lei Cui,Yan Zhang,Kun Jiang,Zhao-Quan He,Bang-Jing Li,Li-Sheng Ding,Ying-Chun Chen,* “Organocatalytic and highly enantioselective direct-amination of aromatic ketones”,Org. Lett. 2007,9,3671.

3. Tian-Yu Liu,Hai-Lei Cui,Qian Chai,Jun Long,Bang-Jing Li,Yong Wu,Li-Sheng Ding,Ying-Chun Chen,* “Organocatalytic asymmetric Friedel-Crafts alkylation/cascade reactions of naphthols and nitroolefins”,Chem. Commun. 2007,2228.

4. Lin Jiang,Hong-Ting Zheng,Tian-Yu Liu,Lei Yue,Ying-Chun Chen,* “Asymmetric direct vinylogous carbon-carbon bond formation catalyzed by bifunctional organocatalysts”,Tetrahedron 2007,63,5123.

5. Tian-Yu Liu,Hai-Lei Cui,Jun Long,Bang-Jing Li,Yong Wu,Li-Sheng Ding,Ying-Chun Chen,* “Organocatalytic and highly stereoselective direct vinylogous Mannich reaction”,J. Am. Chem. Soc. 2007,129,1878.

6. Wei Chen,Wei Du,Lei Yue,Rui Li,Yong Wu,Li-Sheng Ding and Ying-Chun Chen,* “Organocatalytic enantioselective indole alkylations of,?-unsaturated ketones”,Org. Biomol. Chem. 2007,5,816.

7. Jian-Wu Xie,Lei Yue,Wei Chen,Wei Du,Jin Zhu,Jin-Gen Deng and Ying-Chun Chen,* “Highly enantioselective Michael addition of cyclic 1,3-dicarbonyl compounds to,?-unsaturated ketones”,Org. Lett. 2007,9,413.

8. Jian-Wu Xie,Wei Chen,Rui Li,Mi Zeng,Wei Du,Lei Yue,Ying-Chun Chen,* Yong Wu,Jin Zhu,and Jin-Gen Deng,* “Highly asymmetric Michael addition of,?-unsaturated ketones catalyzed by 9-amino-9-deoxyepiquinine”,Angew. Chem.,Int. Ed. 2007,46,389.

9. Tian-Yu Liu,Rui Li,Qian Chai,Jun Long,Bang-Jing Li,Yong Wu,Li-Sheng Ding,Ying-Chun Chen,* “Enantioselective Michael addition of-substituted cyanoacetates to vinyl ketones catalyzed by bifunctional organocatalysts”,Chem.?Eur. J. 2007,13,319.

10. Wei Chen,Xiang-Hong Yuan,Rui Li,Wei Du,Yong Wu,Li-Sheng Ding,Ying-Chun Chen,* “Organocatalytic and stereoselective [3 + 2] cycloadditions of azomethine imines with,?-unsaturated aldehydes”,Adv. Synth. Catal. 2006,348,1818.

11. Wei Chen,Rui Li,Yong Wu,Li-Sheng Ding,Ying-Chun Chen,* “Self-supported thiourea-palladium complexes: highly air-stable and recyclable catalysts for the Suzuki reaction in neat water”,Synthesis 2006,3058.

12. Lin Jiang,Tong-Fei Wu,Ying-Chun Chen,* Jin Zhu,Jin-Gen Deng,* “Asymmetric transfer hydrogenation catalysed by hydrophobic dendritic DACH-rhodium complex in water”,Org. Biomol. Chem. 2006,4,3319.

13. Tian-Yu Liu,Jun Long,Bang-Jing Li,Lin Jiang,Rui Li,Yong Wu,Li-Sheng Ding,Ying-Chun Chen,* “Enantioselective construction of quaternary carbon centre catalysed by bifunctional organocatalyst”,Org. Biomol. Chem. 2006,4,2097.

14. Qing-Ping Liu,Ying-Chun Chen,* Yong-Wu,Jin Zhu,Jin-Gen Deng,* “Self-supported heterogeneous star-shaped oxime-palladacycle catalysts for the Suzuki coupling reaction”,Synlett 2006,1503.

15. Yan-Kai Liu,Rui Li,Lei Yue,Ying-Chun Chen,* Yong Wu,Li-Sheng Ding,“Unexpected ring-opening reactions of aziridines with aldehydes catalyzed by nucleophilic carbenes under aerobic conditions”,Org. Lett. 2006,8,1521.

16. Jian-Wu Xie,Lei Yue,Dong Xue,Xiao-Li Ma,Ying-Chun Chen,* Yong Wu,Jin Zhu,Jin-Gen Deng,* “Organocatalytic and direct asymmetric vinylogous Michael addition of,?-dicyanoolefins to,?-unsaturated aldehydes”,Chem. Commun. 2006,1563.

17. Wei Chen,Rui Li,Bo Han,Bang-Jing Li,Ying-Chun Chen,* Yong Wu,Li-Sheng Ding,Dan Yang,“Design and synthesis of bis-thiourea ligands and their application in Pd-catalyzed Heck and Suzuki reactions under aerobic condition”,Eur. J. Org. Chem. 2006,1177.

18. Zhi-Quan Yong,Xiao-Ping Xu,Ying-Chun Chen,* Xu Bao,Ling-Ling Weng,* Hu Zheng,“Synthesis and cytotoxic activity of novel water-soluble prodrugs of combretastatin A-4”,Chin. Chem. Lett. 2006,17,23.

19. Dong Xue,Ying-Chun Chen,* Qi-Wei Wang,Ling-Feng Cun,Jin Zhu,Jin-Gen Deng,* “Asymmetric direct vinylogous Michael reaction of activated alkenes to nitroolefins catalyzed by modified cinchona alkaloids”,Org. Lett. 2005,7,5293.

20. Bang-Jing Li,Lin Jiang,Min Liu,Ying-Chun Chen,* Li-Sheng Ding,Yong Wu,“Asymmetric Michael addition of thiols to,?-unsaturated carbonyl compounds catalyzed by bifunctional organocatalyst”,Synlett 2005,603.

21. Dong Xue,Ying-Chun Chen,Qi-Wei Wang,Xin Cui,Jin Zhu,Jin-Gen Deng,“Transfer hydrogenation of activated C=C bonds catalyzed by ruthenium amido complexes: reaction scope,limitation,and enantioselectivity”,J. Org. Chem. 2005,70,3584.

22. Ying-Chun Chen,* Tong-Fei Wu,Lin Jiang,Xin Cui,Jin-Gen Deng,* Jin Zhu,Yao-Zhong Jiang,“Synthesis of dendritic ligands and application in asymmetric transfer hydrogenation”,J. Org. Chem. 2005,70,1006.

23. Chun-Yu Ho,Ying-Chun Chen,Man-King Wong,Dan Yang,“Fluorinated chiral secondary amines as catalysts for epoxidation of olefins with oxone”,J. Org. Chem. 2005,70,898.

24. Dan Yang,* Ying-Chun Chen,Nian-Yong Zhu,“Sterically bulky thioureas as air- and moisture-stable ligands for Pd-catalyzed Heck reactions of aryl halides”,Org. Lett. 2004,6,1577.

25. Ying-Chun Chen,Dong Xue,Jin-Gen Deng,Xin Cui,Jin Zhu,Yao-Zhong Jiang,“Efficient asymmetric transfer hydrogenation of activated olefins catalyzed by ruthenium amido complexes”,Tetrahedron Lett. 2004,45,1555.

26. Pei Nian Liu,Ying Chun Chen,Xue Qiang Li,Yong Qiang Tu,Jin Gen Deng,“Dendritic catalysts for asymmetric transfer hydrogenation based on (1S,2R)-norephedrine derived ligands”,Tetrahedron: Asymmetry 2003,14,2481.

27. Ying-Chun Chen,Tong-Fei Wu,Jin-Gen Deng,Hui Liu,Xin Cui,Jin Zhu,Yao-Zhong Jiang,Michael C. K. Choi and Albert S. C. Chan,“Multiple dendritic catalysts for asymmetric transfer hydrogenation”,J. Org. Chem. 2002,67,5301.

28. Ying-Chun Chen,Tong-Fei Wu,Jin-Gen Deng,Hui Liu,Yao-Zhong Jiang,Michael C. K. Choi and Albert S. C. Chan,“Dendritic catalysts for asymmetric transfer hydrogenation”,Chem. Commun. 2001,1488.

29. Peilian Liu,Yingchun Chen,Jingen Deng,Yongqiang Tu,“Efficient method for the preparation of benzylic bromides”,Synthesis 2001,2078.

獲獎記錄

1. 2007年 四川省第九屆青年科技獎。

2. 2007年 藥明康德生命化學研究獎(三等)。

3. 2011四川省有突出貢獻的優秀專家。

4. 2011年國家傑出青年科學基金。

5. 2012 Thieme Journal Award。

6. 2012 Asia Core Program Lectureship Award。

7. 2013年全國百篇優秀博士學位論文指導教師。

8. 2014年中國化學會青年手性化學獎。

9. 2014年科技部科技創新人才推進計畫青年領軍人才。

10. 2015年四川省衛生計生領軍人才 。

2007年獲四川省第九屆青年科技獎。

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