雷新胜
药物化学, 副研究员, 硕士生导师

姓      名

 雷新胜

性      别

 男

职      称

 副研究员

学      历

 博士

电      话

 021-51980128

传      真

 021-51980128

电子邮件

 leixs@fudan.edu.cn

个人主页

 无

通讯地址

 张衡路826号化学南楼319室

教育经历 1986.09 – 1990.06 南开大学化学系 学士
1990.09 – 1993.06 南开大学化学系 硕士
1996.09 – 1999.08 中国协和医科大学&中国医学科学院药物研究所 博士

工作经历 1999.09 – 2001.07 中国科学院上海有机化学研究所,博士后
2001.11 – 2003.12 法国国立应用科学研究院(INSA de Rouen),博士后
2004.01 – 2007.06 上海恒瑞医药科技有限公司,研发中心研究员
2007.07 – 至今 复旦大学药学院药化教研室,副研究员
2012.06 – 2012.07     法国国立应用科学研究院(INSA de Rouen),“invited professor”

职务 硕士生导师


主要科研贡献
在化学合成新方法的基础研究以及将基础研究成果向新药开发研究方面取得了一系列重要进展,主要包括:

1. 从原子经济性角度出发,设计并建立了从2-氨基吡啶、醛、炔三种简单原料一步合成咪唑并吡啶杂环,建立了新颖高效、符合现代绿色化学要求、用途广泛的方法,并将该方法应用于安眠药唑吡坦的合成,开发出了唑吡坦的新型合成工艺和成功实施了专利转让。

2. 通过对ɑ、β-不饱和的羰基化合物的ɑ-烷基化反应,立体选择性地构建了具有多用途的全碳季碳手性砌块,并将其成功地应用于补骨脂酚、异补骨脂酚及其构效关系研究中,经相关体外活性评价,从中发现了具有抗肿瘤活性且具进一步开发潜力的类天然产物。

3. 发展了新的合成氟代烯烃的化学方法, 基于选择性抑制I型组蛋白去乙酰化酶的海洋天然产物Largazole的结构,设计合成了一系列氟代Largazole类似物, 经相关体外活性评价,从中发现了具有显著的抗肿瘤活性且具进一步开发潜力的类天然产物, 为进一步开展海洋天然产物的新药研究奠定了基础。

4. 近年来,以通信作者发表SCI论文20余篇,以第一发明人获授权中国专利8项 (转让1项)。


承担科研项目情况

1. 深海动植物药物先导化合物高效挖掘与候选药物成药性研究(课题6:深海动植物来源候选药物系统成药性评价,子课题) 国家重点研发计划 (项目批准号:2018YFC0310900,60万,参与)

2. ɑ2C-肾上腺素受体拮抗活性导向的新型咪唑并[1,2-a]吡啶类化合物的合成研究国家自然基金面上项目 (项目批准号:21472024,2015.01-2018.12,85万,主持)

3. 海洋天然产物Mollamide氟代烯烃类似物的合成与生物活性评价研究

国家自然基金委专项基金项目(项目批准号:21242008,2013.01-2013.12,10万元, 主持)

4. 海洋药物候选物的结构改造与化学全合成 国家高技术研究发展计划863项目(项目批准号:20872019,2013.01-2015.12,50万元,参与)

5. 基于penicillide结构的类天然产物合成及其胆固醇酯转运蛋白抑制的研究 国家自然基金面上项目(项目批准号:20872019, 2009.01-2011.12,32万元,主持)


研究方向

1. 合成方法学及药物合成工艺研究
2. 基于天然产物的新药研究

 

代表性论著
1. Bingbing Zhang; Jiami Liu; Dingding Gao; Xiaolin Yu; Jinlei Wang; Xinsheng Lei* A fluorine scan on the Zn2+-binding thiolate side chain of HDAC inhibitor largazole: synthesis, biological evaluation, and molecular modeling European Journal of Medicinal Chemistry 2019 (accepted, DOI:10.1016/j.ejmech.2019.111672)

2. Bingbing Zhang, Guangsheng Shan, Yinying Zheng, Xiaolin Yu, Zhu-Wei Ruan, Yang Li, Xinsheng Lei* Synthesis and Preliminary Biological Evaluation of Two Fluoroolefin Analogs of Largazole Inspired by the Structural Similarity of the Side Chain Unit in Psammaplin A Marine Drugs 2019, 17, 333-346.

3. Chao Huang, Juan Xiong, Hui-Da Guan, Chang-Hong Wang, Xinsheng Lei,* Jin-Feng Hu* Discovery, synthesis, biological evaluation and molecular docking study of (R)-5-methylmellein and its analogs as selective monoamine oxidase A inhibitors Bioorganic & Medicinal Chemistry 2019, 27, 2027–2040.

4. Qiaoning Ma, Xiaodi Yang, Xinsheng Lei*, Guo-Qiang Lin* A highly enantioselective synthetic method towards the α2c-adrenoceptor antagonist ORM-10921 Organic Chemistry Frontier 2019, 6, 773–779.

5. Yuheng Wang, Bingbing Zhang, Yinying Zheng, Qiaoning Ma, Qiang Sui, Xinsheng Lei* Practical and scalable preparation of Minodronic acid and Zolpidem from 2-chloroimidazole[1,2-a]pyridines Tetrahedron 2019, 75, 1064-1071.

6. Yue Wu, Bingbing Zhang, Yinying Zheng, Yuheng Wang, Xinsheng Lei* Cs2CO3-promoted defluorination and functionalization of a-CF3 carbonyl compounds in the presence of N-, O-, and/or S-nucleophiles RSC Advances, 2018, 8, 16019–16023.

7. Xiaoling Yu, Bingbing Zhang, Guangsheng Shan, Yue Wu, Feng-Ling Yang, Xinsheng Lei* Synthesis of the molecular hybrid inspired by Largazole and Psammaplin A Tetrahedron 2018, 74, 549-555.

8. Liu, Hui-juan; Jiang, Xiao-xiao; Guo, Yi-zhen; Sun, Fang-hui; Kou, Xin-hui; Bao, Yong; Zhang, Zhu-qing; Lin, Zhao-hu; Ding, Ting-bo; Jiang, Lan; Lei, Xin-sheng; Yang, Yong-hua*. The flavonoid TL-2-8 induces cell death and immature mitophagy in breast cancer cells via abrogating the function of the AHA1/Hsp90 complex Acta Pharmacologica sinica 2017, 38, 1381-1393.

9. Zhang, Bingbing; Shan, Guangsheng; Ma, Qiaoning; Xu, Qianqian; Lei, Xinsheng* An Improved and Scalable Synthesis of Zolpidem via a CuI/BINOL-mediated Tandem Reaction of Imine and Alkyne Heterocyclic Communications 2017, 23, 445–448.

10. Yang Li, Kai Li, Yue Wu, Qiaoning Ma, Xinsheng Lei* Facile synthesis of fluorovinyl-containing lactams via ring-closing metathesis of N-substituted 2-fluoroallylamides Tetrahedron 2016, 72, 4845-4853.

11. Tu Lang, Ma Qiaoning, Kou Xinhui, Sun Ping*, Yang Yonghua, Lei Xisheng* Synthesis of 8-Pentanyl Favonoids and Evaluation of Their Inhibition against MDA-MB-231 Cell Proliferation Chin. J. Org. Chem. 2015, 35, 1551-1558.

12. Qun Zhao, Qianqian Xu, Guangsheng Shan, Chao Dong, Hong Zhang*, Xinsheng Lei* Synthesis of ?3-2-Hydroxybakuchiol Analogues and Their Growth Inhibitory Activity against Rat UMR106 Cells Molecules 2014, 19, 2213-2225.

13. Qian-Qian Xu, Qun Zhao, Guang-Sheng Shan, Xi-Cheng Yang, Qi-Yuan Shi, Xinsheng Lei* A facile asymmetric synthesis of ?3-2-Hydroxybakuchiol Bakuchiol and ent-Bakuchiol Tetrahedron 2013, 69(50), 10739-10746.

14. Qiao Zhang, Chunlin Deng, Lisong Fang, Wenwei Xu, Qun Zhao, Jiange Zhang*, Yiping Wang, Xinsheng Lei* Synthesis and Evaluation of the Analogues of Penicillide against Cholesterol Ester Transfer Protein Chin. J. Chem. 2013, 31, 355-370.

15. Deng, Chun-Lin; Zhang, Qiao; Fang, Lisong; Lei, Xinsheng*; Lin, Guo-qiang*. A Convergent Approach to Dibenzodioxocinones: Synthesis of Racemic Penicillide. Helv. Chim. Acta 2012, 95 (4), 626-635.

16. Liu, Ping; Xu, Qian-Qian; Dong, Chao; Lei, Xinsheng*; Lin, Guo-qiang*. A Complementary Approach to 3,5-Substituted Pyrazoles with Tosylhydrazones and Terminal Alkynes Mediated by TfOH. Synlett 2012, 14, 2087-2092.

17. Ping Liu, Chun-Lin Deng, Xinsheng Lei*, Guo-qiang Lin*. Tandem Amination/Cycloisomerization of Aryl Propargylic Alcohols with 2-Aminopyridines as an Expedient Route to Imidazo[1,2-a]pyridines. Eur. J. Org. Chem. 2011, 7308–7316.

18. Fang, Li Song; Zhang, Qiao; Deng, Chun Lin; Lei, Xin Sheng*; Lin, Guo Qiang. Regioselective chlorination of vinca alkaloids catalyzed by Lewis acid. Science China: Chem. 2011, 54(7), 1039-1043.

19. Zhang, Jiange*; Liu, Xianbo; Lei, Xinsheng*; Wang, Lei; Guo, Lihe*; Zhao, Gang; Lin, Guoqiang. Discovery and synthesis of novel luteolin derivatives as DAT agonists. Bioorg. Med.Chem. 2010, 18(22), 7842-7848.

20. Liu, Ping; Fang, Li-song; Lei, Xinsheng*; Lin, Guo-qiang*. Synthesis of imidazo[1,2a]pyridines via three-component reaction of 2-aminopyridines, aldehydes and alkynes. Tetrahedron Lett. 2010, 51(35), 4605-4608.

21. Shi, Lei; Lei, Xinsheng*; Zhang, Jiange*; Lin, Guoqiang. Synthesis of Racemic ?3-2-Hydroxybakuchiol and Its Analogues. Helv. Chim. Acta 2010, 93(3), 555-564.

22. Lei, Xinsheng; Yu, Xiangda; Yin, Long; Liu, Zhenhong; Tang Peng Cho* Symthesis and Biological Evaluation of C-12’ Substituted Vinflunine derivatives Bioorg. Med. Chem. Lett. 2008, 18, 4602-4605.

 

打印 返回