A Practical Route to Neokotalanol and Its Natural Analogues

Release date:2019-04-15  Release:主页英文版

     Angewandte Chemie Internatinal Edition (IF 12.102), the top journal of chemistry, has published the latest research results of CPU School of Pharmacy: A Practical Route to Neokotalanol and Its Natural Analogues, Sulfonium. Sugars With Antidiabetic Activities, with China Pharmaceutical University as the first author institution, Master’s candidate HUANG Yuhao as the first author,  Professor WU Xiaoming and Associate Professor XIE Weijia as the correspondent authors.

     The strontium salt active natural products Neosalaprinol, Neosalacinol, Neoponkoranol and Neokotalanol extracted from the roots of the genus Cryptopsis have novel and unique chemical structures and strong α-glucosidase inhibitory activities. Its separation and identification, total synthesis and structural modification have always been the research hotspots in the fields of medicinal chemistry and organic synthetic chemistry. The Salacia L. plant extract containing these active molecules has been developed into a health food for hypoglycemic and weight loss and has been marketed in Japan. However, such natural products, especially Neokotalanol, have complex structures and many chiral centers, and currently lack efficient synthesis methods. In this research work, researchers have developed a new synthetic strategy that uses diiodopentaerythritol and polyhydroxy thiol as core synthons through tandem (intermolecular and intramolecular) nucleophilic substitution reactions. The core skeleton of the five-membered cyclic strontium salt was successfully constructed. The strategy simultaneously solves the problems of long reaction route, poor intermediate stability and unsatisfactory stereoselectivity of the coupling reaction in the conventional synthesis method. This work is also the first report on the general synthetic method of this kind of active natural products, which is of great significance for its subsequent related pharmaceutical research. At the same time, it has important reference value for the synthesis of related thiofuranose and saccharide small molecule containing ruthenium ion skeleton structure.

  

     The research was supported by the National Natural Science Foundation of China, the Jiangsu Provincial Natural Science Foundation Outstanding Youth Fund, and the China Pharmaceutical University's “Double-Class Construction” project.