Nowadays, health is becoming an increasingly frequent topic for discussion of everyday life. However, cancer, cardiovascular and cerebrovascular diseases and diabetes and many other diseases are still a big concern for people. Development of small molecule drugs is now an important approach to treatment of those diseases. Since its founding in 2012, the research team led by Professor Li Yang of the School of Chemistry and Chemical Engineering has been focusing on researches of efficient synthesis of substituted aromatic hydrocarbon, and devoted to assisting the synthetic chemists and pharmaceutical chemists in developing greener and more convenient synthetic routes, so as to obtain molecules with significant medicinal value. Recently, the research team has made another breakthrough in the research area. The achievement has been published on Journal of the American Chemical Society (factor of influence 13.038) (2018, 140, 3555-3559). The paper was well received by the editors and reviewers of the journal, and was selected as the inside cover paper (Fig. 1).
Fig. 1 New-generation domino aryne reagent and the research findings in the area in recent years
Recently, in the continuous exploration of utilization of aryne intermediate synthesis to synthesize polysubstitution aryne, the research team led by Li Yang has achieved a series of research findings, such as J. Am. Chem. Soc. (2015, 137, 5670-5673; 2016, 138, 10814-10817; 2017, 139, 623-626) and Org. Lett. (2016, 18, 3130-3133; 2016, 18, 3726-3729) (Fig. 1). As shown in 2a, in the latest research, the research team has developed a new-generation domino aryne reagent and realized for the first time the efficient and well-aligned tandem of arynophile of two different types in transformation of domino aryne (Fig. 2b). The substrate of the chemical conversion has a wide application range, satisfactory reaction efficiency and stereospecificity. Compared with the traditional synthetic benzoheterocycle strategy, which generally involves several preparation steps, this method can be used to generate products of benzo ring system, and build polycyclic systems containing the quaternary carbon center all in one step. In addition, it has advantages such as high synthesis flexibility, and outstanding diastereoselectivity.
Fig. 2: a. Domino aryne precursors of two generations; b. Efficient preparation of new-type benazepine rings; c. Structural reorganization of androstanolone, an androgens; d. Ibutamoren mesylate for treatment of midgetism
In addition, the research group has reorganized the structure of androstanolone, an androgens by converting the cyclohexanone contained in it into a benzpyrole derivative with spirane structure (as shown in Fig. 2c). Furthermore, the research team has developed a new route to synthesize a new drug to treat growth hormone deficiency (also called midgetism), ibutamoren mesylate, through the nucleophilic-ene reaction cascading process of domino aryne (Ibutamoren was developed by Ammonett Pharma and appeared on the market in the USA in 2017) (Fig. 2d). This demonstrated the noticeable potential of application of Domino aryne nucleophilic-ene reaction in synthesis of natural products and pharmaceutical molecules. The research findings were achieved jointly by two students, Xu Hai and He Jia.
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