An Important Advances in Total Synthesis of Natural Product Li Group’s Paper Published in JACS

2015-01-02

Recently,Prof. Li in the Department of Chemistry together with his team (http://www.ligroup.com.cn) publisheda paper named “Collective Synthesis of Humulanolides Using a Metathesis CascadeReaction” in JACS (J. Am. Chem. Soc. 2014, 136, 13610), which is one of the most famous journal ofChemistry internationally. Dr. Jing-chun Han is the first author andChuang-chuang Li is the correspondent author. They both work in SouthUniversity of Science and Technology of China. This work is an importantadvance in total synthesis of natural product, which will lay a foundation forthe further research on innovative anti-tumor medicines with independentintellectual property right.

Natural products and its derivatives have provided themost important sources in innovative medicine discovery, which is also animportant molecular tool in bio-medical research. At present, more than 50%medicines used clinically are extracted directly or indirectly from natural products.However, the natural products are so difficult to get that it’s difficult tokeep pace with the demands of different researches. Therefore, the research of synthesizingnatural products is not only important for the modernization of Chinesetraditional medicine, but also has strategic importance in the research ofinnovative medicines. Li Group is actively engaged inthe Lead-Compound-Oriented total synthesis of a number of complex, biologicallyactive natural products. They continuously developinnovative methods and strategies (Angew.Chem. Int. Ed. 2014, 53, 11051), which allowfor rapid access to the target structure and the analogs to enable the study ofotherwise unexplored biological phenomena (Org. Lett.2014, 16,4380;Angew. Chem. Int. Ed. 2013, 52, 620). 

The humulanolides are a series of sesquiterpene lactones,and most of the compounds belonging to this class have a unique and challengingstructure. Several humulanolide compounds have been reported to exhibit anticanceractivity. For example, asteriscunolide A induces apoptosis in human cancer celllines and asteriscunolide D has more cytotoxicity than cisplatin, with goodpotency against the HT-29 (human colon carcinoma), A-549 (human lungcarcinoma), and MEL-28 (human melanoma) cell lines. This means that they may become newpotential anticancer drugs. Taken together, the fascinatingstructural motifs and promising pharmacological properties of humulanolideshave prompted significantinterest in the synthetic community (including Wender and Trost in Standford University, Zhi-xiangXu of Peking University and so on). 

Li group have developed a highly concise and asymmetricsynthesis of a series of humulanolides in 5−7 steps without the requirement forany protecting groups. Notably, this includes the first reported synthesis of6,7,9,10-tetrahydroasteriscunolide and 6,7,9,10- tetradehydroasteriscanolide.The challenging 11-membered ring and fused butenolide moieties of biologicallyactive asteriscunolide D were successfully installed in only one step using anovel ROM/RCM cascade reaction. This work represents the first reportedexample of an intramolecular ROM/RCM cascade reaction for the construction of abicyclic skeleton with an 11-membered ring. Furthermore, they have demonstratedthat asteriscunolide D can be used as a versatile biomimetic syntheticprecursor for the construction of several other humulanolides. 

This work was supported by the NaturalScience Foundation of China and the national 973 Program. 

Paper link:http://pubs.acs.org/doi/abs/10.1021/ja5084927

Group Website:http://www.ligroup.com.cn