Akuammiline家族天然产物分离于我国传统药用植物灯台叶,对该家族生物碱的现代药学研究揭示了广泛的生物学活性,包括抗癌、镇痛、抑制耐药性等。由于其新颖的化学结构和显著的生物活性,对该家族生物碱的研究成为近10年的科学热点,推动了相应合成化学、化员工物学以及药物化学的发展。从2012年开始,我课题组围绕该家族天然产物从事科学研究,构建我们的研究体系,我们的学术成果及研究特色如下:
1、我们发展的“indoxyl-based strategy via aza-pinacol rearrangement”合成策略对该类天然产物的合成提供了概念上全新的断键策略(
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, 9217)。基于该策略及其相应方法学拓展,我们实现了天然产物minfiensine的化学合成、该家族结构最为独特的天然产物calophyline A的首次化学全合成(
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, 2754)、首次实现了对结构多样性的akuammiline生物碱deformylcorymine、strictamine以及calophyline A的集体性全合成(
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2、通过与白菜网注册领取体验医学院张敬仁教授课题组合作,我们对所构建的化合物进行活性评价以及基于立体化学的构效关系研究(SARs),发现一个手性先导化合物可以作为抗生素佐剂(antibiotic adjuvant),使耐甲氧西林金黄色葡萄球菌(MRSA)重新对b-内酰胺类抗生素敏感(
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, 9217)。鉴于抗生素的耐药性已经成为全球性难题,而新型抗生素的研发越来越困难,我们开展的抗生素佐剂策略具有很多优势,比如可以延长现有抗生素的使用周期以及不易诱导新的耐药性等。
2008 国家优秀自费职工奖学金
2017 Thieme Chemistry Journal Award
2017
Bayer Investigator Award, 2017
代表性论文
1. Unified Total Syntheses of Structurally Diverse Akuammiline Alkaloids. Xie, X.; Wei, B.; Li, G.;
Zu, L.*
Org. Lett.
2017,
19, 5430.
2. Catalytic Enantioselective Aza-pinacol Rearrangement. Yu, Y.; Li, J.; Jiang, L.; Zhang, J.-R.;*
Zu, L.*
Angew. Chem. Int. Ed.
2017,
56, 9217.
3. Total synthesis of (±)-Grandilodine B. Wang, C.; Wang, Z.; Xie, X.; Yao, X.; Li, G.;
Zu, L.*
Org. Lett.
2017,
19, 1828.
4. Bio-Inspired Fragmentations: Rapid Assembly of Indolones, 2-Quinolinones, and (-)-Goniomitine. Li, H.; Cheng, P.; Jiang, L.; Yang, J.;
Zu, L.*
Angew. Chem. Int. Ed.
2017,
56, 2754.
5. Total Synthesis of Calophyline A. Li, G.; Xie, X.;
Zu, L.*
Angew. Chem. Int. Ed.
2016,
55, 10483. This paper was selected as the back cover:
Angew. Chem. Int. Ed.
2016,
55, 10524.
6. Divergent Synthesis of Hydro-g-Carbolines and Multisubstituted Indoles through Grob Fragmentation/Mannich Cyclization. Jiang, L.; Yu, Y.; Li, G.;
Zu, L.*
Chem. Asian J.
2016,
11, 2838.
7. The Development of Aza-Pinacol and Aza-Semipinacol Rearrangements for the Synthesis of Nitrogen-Containing Molecules. Yu, Y.; Li, G.;
Zu, L.*
Synlett.
2016,
27, 1303. (invited Synpacts)
8. An Indoxyl-Based Strategy for the Synthesis of Indolines and Indolenines. Yu, Y.; Li, G.; Jiang, L.;
Zu, L.*
Angew. Chem. Int. Ed.
2015,
54, 12627.
9.
tert-Butyl Hypochlorite Mediated Diastereoselective Oxidative Coupling: Access to 1- Functionalized Tetrahydrocarbazoles. Jiang, L.; Xie, X.;
Zu, L.
*
RSC Adv.
2015,
5, 9204.
10. Rapid Assembly of Functionalized Hydrodibenzofurans via Semipinacol Rearrangements. Yao, X.; Xie, X.; Wang, C.;
Zu, L.
*
Org. Lett.
2015,
17, 4356.
11. [3 + 2] Annulations between Indoles and a, b-Unsaturated ketones: Access to Pyrrolo[1,2-a] Indoles and Model Reactions toward the Originally Assigned Structure of Yuremamine. Li, H.; Wang, Z.;
Zu, L.
*
RSC Adv.
2015,
5, 60962.
12. Efficient Assembly of Polysubstituted Pyrroles via a (3+2) Cycloaddition/Skeletal Rearrangement/Redox Isomerization Cascade Reaction. Yu, Y.; Wang, C.; He, X.; Yao, X.;
Zu, L.
*
Org. Lett.
2014,
16, 3580.