Research group of Wan Qian and Zeng Jing, Huazhong University of science and technology: hydrogen bond assisted reagent effect controlled rare 3-aminosugar β - glycosylation

Introduction 3,5-trans-3-amino-2,3,6-trioxypyranose (3,5-trans-3-amino sugar) is widely found in some antibiotics with good biological activity, and its connection mode is mainly β - glucoside bond Due to the lack of o-participating groups in C2 position of these rare sugars, and the high instability of β - glucoside bond itself, and the heterocephalic carbon effect is more conducive to the formation of α - glucoside bond, the construction of β - glucoside bond of 3,5-trans-3-amino sugar is very challenging, so far, there are few reports on β - selective glycosidization of 3,5-trans-3-amino sugar Recently, Professor Wan Qian and Zeng Jing of Tongji School of medicine, Huazhong University of science and technology realized the selective glycosidization of 3,5-trans-3-aminosugar by using the effect of exogenous nucleophilic reagent assisted by hydrogen bond, and applied it to the modification of a series of active molecules The results were published online in J am Chem SOC (DOI: 10.1021 / JACS 9b01862) Professor Wan Qian and Zeng Jing brief introduction of the research group the research fields of the research group include the development of chemical synthesis methods and Strategies of sugar, the design and synthesis of biologically active organic small molecules, free radical chemistry and water-phase organic reactions, the synthesis and activity evaluation of biologically active oligosaccharides and the discovery of sugar drugs, etc The research group published dozens of academic papers in J am Chem SOC., angel Chem Int ed., green chem And other internationally renowned journals, and applied for and was authorized with a number of patents At present, the research group has two professors, two associate professors and many doctors and masters Website of the research group: http://sugar.pharm.hust.edu.cn Frontier research achievements: hydrogen bond assisted reagent effect controlled β - glycosylation of rare 3-amino sugars although the content of 3,5-trans-3-amino sugars is rare in nature, but the compounds with this structure usually have very good activity, so it is of great significance to develop the synthesis and glycosylation methods of these rare sugars for the discovery of new leading compounds of sugar drugs However The construction of β - glycosidic bonds of these sugars is very challenging, and there are only a few successful examples (McDonald, org Lett 2009, 11, 4850; Bennett, org Lett 2018, 20, 4695; danishefsky, chem EUR J 2014, 20, 8731) In view of 3, The C3 amino group of 5-trans-3-aminosaccharide is located at the vertical bond position, and the strong electron absorbing amino protecting group makes the amino group a good hydrogen bond donor Professor Wan Qian and Zeng Jing's team consider introducing an exogenous nucleophile, which can be used with C3- The amino group is bound by hydrogen bond, and under the guidance of the hydrogen bond force, it further binds with the activated amino sugar donor by covalent bond in the heterocephalic carbon position, so as to construct a relatively stable Alfa surface shielded six membered ring intermediate The existence of this intermediate makes the glycosylation receptor preferentially attack from the β surface, so as to achieve 3, Efficient β - selective glycosylation of 5-trans-3-aminosaccharides (Fig 1) Fig 1 The principle of β - selective glycosylation mediated by the effect of exogenous nucleophiles assisted by hydrogen bond (source: J am Chem SOC.) based on the characteristics that the 3-amino-sugar β - glycoside bond can be effectively stabilized under mild gold catalytic conditions, the author screened various exogenous nucleophiles under the condition of Yu glycosylation, and finally found triaryloxyphosphine Class a additives have the best effect With triphenylphosphine oxide or more electron rich tris (3,5-dimethyl-4-methoxyphenyl) phosphine oxide as the additive, the substrate applicability of this method was investigated It was found that all kinds of 3-amino sugar donors and all kinds of receptors can be effectively coupled, and better β - selectivity was given With this method, some natural products and drugs can also be modified by 3-aminosugar β - glycosylation (Fig 2) This method can also be successfully applied to the synthesis of avidino rubicin (Fig 3) Figure 2 Study on the application scope of substrate (source: J am Chem SOC.) Figure 3 Avidinorubicin trisaccharide fragment synthesis (source: J am Chem SOC.) this method is quite different from the known Alfa glycosylation method mediated by exogenous nucleophiles In this method, the stereoselectivity of glycosylation was reversed due to the hydrogen bond effect This difference is further demonstrated by the synthesis of trisaccharide 12 (Fig 4) The importance of hydrogen bond in stereoselectivity of the reaction has been proved by a series of experiments and low temperature NMR studies Figure 4 Synthesis of trisaccharide 12 (source: J am Chem SOC.) in summary, Professor Wan Qian and Professor Zeng Jing's research group successfully realized β - selective glycosylation of 3,5-trans-3-amino sugar with the help of hydrogen bond assisted exogenous nucleophile effect This method laid an important foundation for the synthesis of 3-aminosaccharide bioactive natural products and the discovery of 3-aminosaccharide lead compounds The experiment of this work was mainly completed by Wang ruobin and Zhang Shuxin, master students The low-temperature nuclear magnetic resonance experiment was completed with the help of Fang Jing, Professor Liu Shanshan of Wuhan University, and Dr Zhu Huping of Shanghai Institute of organic chemistry This work was supported by National Natural Science Foundation of China (21772050, 21672077, 21761132014), National Key Laboratory of life organic chemistry (sklbnpc13425) and special fund for basic scientific research of Central University (2016yxms137) Nowadays, people and scientific research have been paid more and more attention in the economic life China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.