刘延凯

作者:蔡超时间:2019-09-03

 

刘延凯

博士

副教授

硕士生导师

科  室:

药物合成化学研究室

办公电话:

0532-82031905

电子邮箱:

liuyankai@ouc.edu.cn

联系地址:

山东省青岛市鱼山路5号中国海洋大学医药学院海洋馆130房间

研究方向:

1. 手性杂环化合物的不对称催化合成

2. 手性小分子药物的不对称催化合成

3. 海洋活性小分子化合物的结构改造

个人简介





主要研究手性有机小分子催化的不对称合成反应在手性小分子药物合成及海洋活性小分子化合物的结构改造中的应用。课题组在过去几年里对手性有机小分子催化剂参与的不对称催化反应进行了深入的研究,相关研究结果在包括Angew. Chem. Int. Ed.J. Am. Chem. Soc.Org. Lett.等高水平国际期刊上发表了30多篇SCI文章,先后主持并多次参与国家自然科学基金项目、山东省自然科学基金项目等。

教育背景





2009.09-2009.12

University of Cologne(科隆大学,德国)

不对称催化合成

交换生,指导老师:Prof. A. Berkessel

2006.09-2010.07

四川大学,华西药学院

不对称催化合成

博士研究生,指导老师:陈应春教授

2004.09-2006.07

四川大学,华西药学院

不对称催化合成

硕士研究生,指导老师:陈应春教授

1998.09-2002.07

山东大学,药学院

药学

本科

工作经历





2013.09~

中国海洋大学,医药学院

副教授


2012.12-2013.09

西南交通大学,生命科学与工程学院

副教授

 

2010.04-2013.04

InstitutCatalàd'InvestigacióQuímicaICIQ研究所,西班牙)

不对称催化合成

博士后研究,指导老师:Prof.  P. Melchiorre

2002.07-2004.08

横店集团成都分子实验室有限公司

医药化工中间研发


荣誉奖励





2011  欧盟,Marie Curie fellowship(玛丽居里奖学金)

承担课程





有机化学I-1(本科生课程)

药物化学(本科生课程)

天然产物全合成(研究生课程)

研究进展

 

 

 

 

课题组的研究工作主要是发现和阐明新的不对称有机催化过程,开发“完美的化学反应”,包括多种不同催化剂参与的联合催化等,以解决合成方法中未解决的问题。最终的目标是开发绿色环保和创新的催化方法,使其在现代有机合成中得到广泛应用。我们通过使用基于有机小分子的不对称选择性催化来实现这一最终目标。

基于海洋来源活性化合物的结构特点,利用上述发展的不对称催化合成策略,对其进行结构改造,并深入研究构效关系,以提高药理活性,降低毒副作用,进而提高其成药性,为发现海洋来源的活性先导化合物并进行产业转化提供物质基础。


代表性成果

代表性论文





1.     Ming, Yong-Chao; Lv, Xue-Jiao; Liu, Ming; Liu,  Yan-Kai*, Synthesis of  Chiral Polycyclic Tetrahydrocarbazoles by  Enantioselective Aminocatalytic Double Activation  of 2-Hydroxycinnamaldehydes with Dienals. Org.  Lett.2021,16, 6515.


2.     Peng, Chen-Jun; Pei, Jun-Ping; Chen, Ying-Han; Wu, Zhi-Yong; Liu, Ming;  Liu, Yan-Kai*, Enantioselective  organocatalytic sequential Michael-cyclization of functionalized nitroalkanes  to 2-hydroxycinnamaldehydes: synthesis of benzofuseddioxa[3.3.1]  and oxa[4.3.1] methylene-bridged compounds. Org.  Chem. Front.2021, 8, 4217


3.  Wu, Hui-Chun; Wang,  Chen; Chen, Ying-Han; Liu, Yan-Kai*,  Asymmetric organocatalytic vinylogous Michael addition triggered  triple-cascade reactions of 2-hydroxycinnamaldehydes and vinylogous  nucleophiles: construction of benzofusedoxabicyclo[3.3.1]nonane  scaffolds. Chem. Commun.  2021,57, 1762.


4.  Zhang, Xiao-Qian; Lv, Xue-Jiao; Pei, Jun-Ping;  Tan, Rui; Liu, Yan-Kai*, An  asymmetric multicatalytic reaction sequence of  2-hydroxycinnamaldehydes and enolic 1,3-dicarbonyl compounds to construct  bridged bicyclic acetals. Org. Chem.  Front. 2020,7, 292.


5.  Pei, Jun-Ping; Lv, Xue-Jiao; Peng, Chen-Jun; Liu, Yan-Kai*, Asymmetric  organocatalytic multicomponent reactions for efficient construction of  bicyclic compounds bearing bisacetal and isoxazolidine moieties. Chem. Commun. 2020,56, 12765.


6.  You, Zhi-Hao; Chen, Ying-Han; Tang, Yu; Liu, Yan-Kai*, Application of E1cB Elimination in Asymmetric  Organocatalytic Cascade Reactions To Construct Polyheterocyclic Compounds. Org. Lett. 2019,21, 8358.


7.  Chen, Ying-Han; Lv, Xxue-Jiao; You, Zhi-Hao; Liu,  Yan-Kai*, Asymmetric organocatalyzed reaction sequence of 2-hydroxy  cinnamaldehydes and acyclic N-sulfonyl ketimines to  construct diverse chiral bridged polycyclic aminals.  Org. Chem. Front. 2019,6, 3725.


8.  Wang, Chen;  Chen, Ying-Han; Wu, Hui-Chun; Wang, Cong; Liu, Yan-Kai*, The  Quinary Catalyst–Substrate Complex Induced Construction of Spiro-Bridged or  Cagelike Polyheterocyclic Compounds via a Substrate-Controlled Cascade Process.  Org. Lett. 2019, 21, 6750.


9.  Chen, Ying-Han;  Lv, Xue-Jiao; You, Zhi-Hao; Liu, Yan-Kai*,  Asymmetric Organocatalyzed Reaction Sequence To Synthesize Chiral Bridged and  Spiro-Bridged Benzofused Aminals via Divergent Pathways. Org. Lett. 2019, 21, 5556.


10.   Xie, Chao-Chao; Tan, Rui;  Liu, Yan-Kai*, Asymmetric Construction  of Polycyclic Indole Derivatives with Different Ring Connectivities  by an Organocatalysis Triggered Two-step Sequence. Org. Chem. Front. 2019, 6, 919.


11.    Qiao, Liang;  Duan, Zhong-Wei; Chen, Ying-Han; Luan, Ye-Peng; Gu, Qian-Qun;  Liu, Yan-Kai*; Li, De-Hai*, Aspergiolides  A and B: Core Structural Establishment and Synthesis of Structural Analogues.  J. Org. Chem. 2019, 84, 4451.


12.   Lv, Xue-Jiao#; Zhao, Wei-Wei#; Chen, Ying-Han; Wan, Sheng-Biao;  Liu, Yan-Kai*, Organocatalytic Asymmetric  Synthesis of Both cis- and trans-Configured Pyrano[2,3-b]chromenes  via Different Dehydration Pathways. Org.  Chem. Front. 2019, 6, 1972.


13.   Lv, Xue-Jiao; Chen, Ying-Han; Liu, Yan-Kai*, Two Competitive but Switchable Organocatalytic Cascade  Reaction Pathways: the Diversified Synthesis of Chiral  Acetal-Containing Bridged Cyclic Compounds. Org. Lett. 2019, 21, 190.


14.   You, Zhi-Hao; Chen, Ying-Han; Tang, Yu; Liu, Yan-Kai*, Organocatalytic Asymmetric Synthesis of Spiro-Bridged  and Spiro-Fused Heterocyclic Compounds Containing Chromane,  Indole, and Oxindole Moieties. Org.  Lett. 2018, 20, 6682.


15.   Wu, Xiao-Na; You, Zhi-Hao; Liu,  Yan-Kai*, Different Hybridized Oxygen Atoms Controlled Chemoselective Formation of Oxocarbenium Ions: Synthesis of  Chiral Heterocyclic Compounds. Org. Biomol. Chem. 2018,  16, 6507.


16.   Qiao, Liang; Duan, Zhong-Wei;  Wu, Xiao-Na; Li, De-Hai*; Gu, Qian-Qun; Liu, Yan-Kai*,  Organocatalytic Diversity-Oriented Asymmetric Synthesis of Structurally and Stereochemically Complex Heterocycles. Org. Lett. 2018, 20, 1630.


17.   Pei, Jun-Ping;  Chen, Ying-Han; Liu, Yan-Kai, Asymmetric Organocatalytic Sequential Reaction of  Structurally Complex Cyclic Hemiacetals and Functionalized Nitro-olefins to  Synthesize Diverse Heterocycles. Org.  Lett. 2018, 20, 3609.


18.   Chen, Ying-Han; Li, De-Hai*; Liu, Yan-Kai*, Diversified Synthesis of Chiral Chromane-Containing Polyheterocyclic  Compounds via Asymmetric Organocatalytic Cascade Reactions. ACS Omega 2018, 3, 16615.


19.   Zhao, Wei-Wei; Liu, Yan-Kai*, Enantio- and  Diastereoselective Synthesis of Tetrahydrofuro[2,3-b]furan-2(3H)-one Derivatives and Related Oxygen  Heterocycles via an Asymmetric Organocatalytic Cascade Process. Org. Chem. Front. 2017, 4, 2358.


20.   You, Zhi-Hao; Chen, Ying-Han; Wu, Xiao-Na; Liu, Yan-Kai*, Lactols  in Asymmetric Sequential Organo- and Gold-catalysis: Synthesis of Densely  Functionalized Epimeric Bicyclic O,O-Acetals.  Adv. Syn. Catal.  2017, 359, 4260.


21.   Liu, Chao; Liu, Yan-Kai*, Asymmetric organocatalytic  one-pot, two-step sequential process to synthesize chiral acetal-containing  polycyclic derivatives from cyclic hemiacetals and enones.  J. Org. Chem. 2017, 82, 10450.


22.   Li, Ji-Yao; Yu, Ke-Wei; Xie, Chao-Chao; Liu, Yan-Kai*, Lactols  in an asymmetric aldol-desymmetrization sequence:  access to tetrahydro-4H-furo[2,3-b]pyran-2-one  and tetrahydro-4H-furo[2,3-b]furan-2-one derivatives. Org. Biomol.  Chem. 2017, 15, 1407.


23.   Chen, Ying-Han;  Sun, Xue-Li; Guan, Hua-Shi; Liu, Yan-Kai*, Diversity-oriented one-pot synthesis to construct  functionalized chroman-2-one derivatives and other heterocyclic compounds. J. Org. Chem. 2017, 82, 4774.


24.   You, Zhi-Hao; Chen, Ying-Han; Liu, Yan-Kai*, From racemic precursors to fully stereocontrolled products: one-pot synthesis of chiral α-amino lactones and  lactams. Org. Biomol.  Chem. 2016, 14, 6316.


25.   Sun, Xue-Li; Chen, Ying-Han; Zhu, Dan-Yang; Zhang, Yan; Liu, Yan-Kai*, Substrate-controlled,  one-pot synthesis: access to chiral chroman-2-one and polycyclic derivatives.  Org. Lett. 2016, 18, 864.


26.    Li, Zhi-Long; Liu, Chao; Tan, Rui*; Tong, Zhi-Ping*; Liu, Yan-Kai*, Organocatalytic, asymmetric [2+2+2] annulation to  construct six-membered spirocyclic oxindoles with six continuous stereogenic centers. Catalysts  2016, 6, 65.


27.   Li, Ji-Yao;  Li, Zhi-Long; Zhao, Wei-Wei; Liu, Yan-Kai*; Tong,  Zhi-Ping; Tan, Rui*, One-pot, highly efficient, asymmetric synthesis of  ring-fused piperidine derivatives bearing N,O- or N,N-acetal moieties. Org. Biomol. Chem. 2016, 14, 2444.


28.   Cai, Pin-Wen; You, Zhi-Hao; Xie, Liang-Hui; Tan, Rui*; Tong, Zhi-Ping*; Liu, Yan-Kai*, The attractive application of lactol  chemistry: from racemic lactol to natural product  skeleton. Synthesis 2016, 48, 2581.


29.   Liu, Yan-Kai*; Li, Zhi-Long;  Li, Ji-Yao; Feng, Huan-Xi; Tong, Zhi-Ping, Open-close:  an alternative strategy to α-functionalization of lactone via enamine catalysis in  one pot under mild conditions. Org.  Lett. 2015, 17, 2022.


30.   Feng, Huan-Xi; Tan,  Rui; Liu, Yan-Kai*, An efficient  one-pot approach to the construction of chiral nitrogen-containing  heterocycles under mild conditions. Org.  Lett. 2015, 17, 3794.


31.   Chen, Cai; Feng, Huan-Xi;  Li, Zhi-Long; Cai, Pin-Wen; Liu, Yan-Kai*; Shan, Lian-Hai; Zhou, Xian-Li*, A highly efficient route to C-3 alkyl-substituted  indoles via a metal-free transfer hydrogenation. Tetrahedron Lett. 2014,  55, 3774.

项目课题

1.    创新中心小分子平台建设项目,CXZX-2-00x,基于半缩醛及半缩醛胺的小分子杂环合成,2018/09-2020/09,在,参与

2.    国自然青年科学基金项目,21302156,基于aza-dienamineaza-trienamine活化历程的不对称催化反应的研究,2014/01/01-2016/12,结题,主持

3.    中央高校基本科研业务费,201562031,海洋活性天然产物分子的设计与合成及构效关系研究,2015/11-2017/12,结题,主持

4.    教育部留学回国人员科研启动基金,教外司留[2015]1098号,海洋来源抗肿瘤化合物Aspergiolide A 的全合成研究及其衍生物制备,2015/06-2017/06,结题,主持

5.    中国海洋大学“青年英才工程”二层次,手性杂环化合物的合成,2013/09-2018/09,结题,主持

6.    6. 联合基金项目,海洋药物与生物制品研究方向二:海洋活性天然产物的成药性优化,U1406402-22015/01-2018/12,结题,参与







 

 

 

关闭