Super synthetic machine: the final solution of small molecule drug development?

About the author: Hou Yingwei, Ph.D in pharmaceutical chemistry, Institute of medicine, Chinese Academy of Medical Sciences, started to carry out research in the Institute of medicine, Chinese Academy of Medical Sciences in 2009 and participated in the research of Bill Gates fund and other projects Since September 2013, he has been engaged in postdoctoral research in school of medicine, Ocean University of China He has published articles in Journal of organizational chemistry, chemistry and biology and other academic journals On March 13, science magazine reported the "super machine" designed by Professor Martin Burke and Dr Junqi li of the University of Illinois at Urbana Champaign with the title of "synthesis of many different types of organic small molecules with one automated process" According to the target molecular structure, the machine can select the prepared molecular components (building blocks) and automatically synthesize them according to the specific mode to get the target molecules The invention has aroused great repercussions in the field of synthetic chemistry Cathleen crudden of Queen's University of Canada says this is a big step forward in small molecule synthesis Others describe the invention as "the end of synthesis." I'm afraid there is still time to prove the impact of this new invention on the field of small molecule organic synthesis However, this synthesis method has great attraction for pharmaceutical chemists The discovery of small drug lead compounds may be achieved by high-throughput screening of tens of thousands of compounds Traditional organic synthesis is target oriented synthesis (TOS), which is difficult to be used in the preparation of large-scale compounds The combination chemistry, which began to rise in the 1990s, provides a solution for pharmaceutical chemists in this respect Through the combination of parallel synthesis and high-throughput screening technology, the discovery efficiency of lead compounds is greatly improved But there are also some problems in combinatorial chemistry and parallel synthesis For example, it is difficult to carry out complex or harsh reaction conditions, most of the synthesized compounds are of the same skeleton or are estimated to be very similar, and the product diversity is not enough Therefore, at the end of last century and the beginning of this century, with the rapid development of organic synthesis technology, the word diversity oriented synthesis (DOS) has entered people's vision DOS has high synthesis efficiency similar to combinatorial chemistry, but also has high product structure diversity Such synthetic technology is exactly what pharmaceutical chemists expect In fact, Professor Burke's "super machine" adopts a similar diversity oriented synthesis method Through simple reaction, it can not only quickly build a small molecular compound library with structural diversity, but also free the chemical synthesis workers from the time-consuming and laborious separation and purification, which can put more experience into the chemical reaction itself Compared with the parallel synthesis of combinatorial chemistry, the same number of compounds can cover more structural types However, if these molecules with various structures are used for activity screening, it will be more likely to find active target molecules We can foresee that if such an invention can be applied in the field of drug research and development, its value will be immeasurable Maybe "super machine" will become the main way and final solution for the discovery of small molecule drug precursor in the future The intellectual property rights of the above articles belong to yaozhi.com If you need to reprint, please indicate the source and the link of this article.