The Qiu Fayang Research Group of the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences collaborated with the research team of Professor Lan Hongbin of Lanzhou University to adopt a new synthetic route design to skillfully complete the full synthesis of the highly difficult natural product molecule Gelsemine. May 21 was published in Nature News. The results of this study indicate that China has reached the international advanced level in the field of organic chemistry, that is, the full synthetic research field of highly difficult natural product molecules. The total synthesis of natural products is the core research area of ​​organic chemistry, and it is closely related to the fields of structural modification, drug synthesis, daily chemical products and pesticide production in the discovery of new drugs, and plays a decisive role. The total synthesis of highly difficult natural product molecules represents the height of the research field in organic chemistry. Gelsemine is a highly complex alkaloid isolated from the genus Hook. Recent studies have found that the alkaloid has analgesic activity similar to morphine but no side effects of morphine. Therefore, Gelsemine may become a new generation of analgesic drugs. Due to the complex structure of Gelsemine, how to build Gelsemine stereoselectively has been a hot topic and a challenge for synthetic chemistry research. Previously there were eight total synthesises of the natural product molecule in the world, of which two were asymmetric total synthesis. Including the complete synthesis of several top synthetic chemistry research groups in the world, the common problem of these total synthesis is the long route, low overall yield, and unsatisfactory synthesis efficiency. Therefore, the total synthesis of Gelsemine remains a major challenge for synthetic chemists around the world. Qiu Fayang's research team used the asymmetric Diels-Alder cycloaddition catalyzed by organic small molecules, the aldol condensation in intramolecular rings, the addition coupling of yttrium oxide, and the intramolecular nucleophilic substitution through cooperation with the research group of Qi Hongbin. The 12-step reaction completes the enantioselective total synthesis of Gelsemine with a total yield of 5% (see X. Chen, S. Duan, C. Tao, H. Zhai, F. Qiu; Nat. Commun. DOI: 10.1038/ Ncomms8204). This is the most effective total synthesis of Gelsemine so far. Not only has the synthesis route been greatly shortened, but the total yield has also multiplied. This achievement has pushed Gelsemine's total synthesis research to a new height, laying a solid foundation for further studying the performance of Gelsemine.
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