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    Home > Research group of Professor Yang you of East China University of science and technology: Gold catalyzed glucosylation of glycosylalkynate donor

    Research group of Professor Yang you of East China University of science and technology: Gold catalyzed glucosylation of glycosylalkynate donor

    • Last Update: 2019-12-05
    • Source: Internet
    • Author: User
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    Introduction sugar, also known as carbohydrate, together with protein, nucleic acid and lipid, is called four important biological macromolecules in the process of life activities Sugar compounds are widely distributed in nature and participate in the regulation of a variety of life activities In order to develop carbohydrate drugs, vaccines and diagnostic reagents, it is necessary to obtain well-defined carbohydrate compounds to evaluate the mechanism of action of glycans in vivo However, due to the micro heterogeneity of sugars, it is difficult to obtain enough pure sugars through the separation and purification of natural products, so chemical synthesis provides an important way for the preparation and modification of natural sugars Recently, the research group of Professor Yang you, School of pharmacy, East China University of science and technology, invented a simple and multi-purpose gold catalyzed glycosidation reaction with glycosylalkynate as donor The alkynate donor of this method is relatively simple in structure, and its preparation is very convenient and flexible It can be prepared from various precursors such as hemiacetal or glucosinolate The substrate of this glycosidization reaction is widely used in gold catalyst or gold catalyst /Under the catalysis of trifluoromethylsulfonic acid, a variety of oligosaccharides with different connection modes were obtained efficiently The glycoalkynate donor of this reaction was applied to the oligosaccharide synthesis based on the latent activation strategy and the multiple orthogonal one pot strategy, which improved the synthesis efficiency of oligosaccharides This glycoside reaction should be successfully applied to the synthesis of tetrasaccharide antigen on the surface of Streptococcus pneumoniae type 3 and α -In the highly convergent synthesis of (1 → 6) linked mannan 32 sugars, high efficiency was demonstrated (org Lett 2019, DOI: 10.1021/acs.orglett.9b03851) Brief introduction of Professor Yang You's research group Professor Yang you of East China University of science and technology was founded in September 2014 The main research directions of the research group are: (1) the synthesis methodology, total synthesis and chemical biology of glycoconjugates and glycoconjugates with important physiological activities; (2) the development of glycodrugs and glycovaccines; (3) the research on the interaction mechanism of glycoproteins and their application in new medical diagnosis tools There are 5 doctoral students and 10 master students in the research group The research group has been recruiting postdoctors and research assistants for a long time We warmly welcome students who are interested in sugar chemistry and sugar drug research to join our research team to explore the field of sugar science together Prof Yang you: Professor of East China University of science and technology, doctoral supervisor In 2004, he graduated from the Department of chemistry, University of science and technology of China with a bachelor's degree Later, it was jointly cultivated by the University of science and technology of China and Shanghai Institute of organic chemistry of the Chinese Academy of Sciences In 2010, it received the doctorate of science from the University of science and technology of China, with the tutor of researcher Yu Biao From August 2010 to June 2014, postdoctoral research was conducted at Max Planck Institute of colloid and interface in Germany, under the guidance of Professor Peter H Seeberger In September 2014, he was an associate professor of the school of pharmacy, East China University of science and technology In September 2015, he was promoted to Professor and employed as doctoral supervisor Member of the sugar Chemistry Committee of the Chinese chemical society He is mainly engaged in the research of sugar chemistry and sugar drugs So far, nearly 40 SCI papers have been published in international famous journals such as chem Rev., J am Chem SOC., NAT Prod Rep., chem SCI., org Lett., green chem., chem Biol., J org Chem., etc., writing one chapter of English academic monograph, applying for four domestic and foreign invention patents (one authorized) Among them, 4 articles were selected as ESI high cited papers or cover papers, and some research work was reported by CBG information, chemistry world, deutschlandfunk and other highlights Won the national "Thousand Talents Program" young talents (2015), Shanghai Pujiang talents (2015), East China University of science and technology young talents (2015), East China University of science and Technology Youth May 4th Medal (201 7), China Pharmaceutical Association - Servier young Pharmaceutical Chemistry Award (201 8), Royal Chemical Society "top 1% highly cited Chinese author" (201 8) (2019) as the spokesperson of item No 107 "element cycle table of Chinese young chemists" of China Chemical Society, and the fifth "President award of young talents" (2019) of East China University of science and technology Leading research achievements: in the past hundred years, glycochemists have developed a variety of effective glycosidization methods and synthesized many bioactive oligosaccharides and glycoconjugates However, due to the complex and diverse structure of sugar chain, there is not a glycosidization method which can be widely applied to the stereoselective construction of all types of glycosidic bonds Among them, due to the unique catalytic mechanism of gold, more attention has been paid to the study of gold catalyzed glycosylation of alkynyl donor In 2008, Yu Biao's research group reported the gold catalyzed glucosylation of glycoo-alkynylbenzoate donor and applied it to the synthesis of various natural products Based on the pursuit of more simple and more suitable substrate glycoside reaction, liming of the University of California, Santa Barbara In 2018, Professor Zhang and his collaborators reported the silver catalyzed glycosidization of glycosylalkynate donors However, the disarmed glycosyl donors with low activity protected by ester groups could not undergo this glycosidization reaction, which severely restricted their application in the synthesis of complex oligosaccharides Professor Yang You's research group has been devoted to the development of new glycoside reactions Recently, a gold catalyzed rearrangement reaction with glycoalkynyl β - carbonyl ester as substrate was reported for the synthesis of 4-o-glycosylated 2-pyranone (J org Chem 2019, 84, 14141 − 14150) Recently, Professor Yang You's research group transformed the trisubstituted alkenes in the above glycoalkyne ester donor into disubstituted alkenes, and invented a simple and multi-purpose gold catalyzed glycosidation reaction with glycoalkyne ester as donor This method can be used not only for armed glycoalkynate donors with high activity, but also for disarmed glycosyl donors with low activity, which provides a new way for the synthesis of complex oligosaccharides and glycoconjugates Firstly, the preparation method of glycosylalkynate donor was investigated (Table 1) It was found that (z) - alkynate and (E) - alkynate were formed by alkynic acid and glycosyl hemiacetal under the promotion of EDCI (1.5 equivalent) and DMAP (1.0 equivalent) In addition, glycoalkynate donor can also be obtained by two steps of condensation of iodoenoic acid with glycosyl hemiacetal and subsequent Sonogashira coupling Glycosylalkynate donor can also be obtained by the conversion of glycosylimine ester or glucoside The results showed that the preparation of glycosylalkynate donor is very flexible, which can be prepared from the common glycosyl hemiacetals, or from the conversion of glycosylimine ester or glucoside Table 1 Preparation of glycosyl alkynate donor (source: org Lett.), then, the author optimized the conditions of glycosylation reaction of glycosyl alkynate donor It was found through the condition screening that under the catalysis of gold catalyst or gold catalyst / trifluoromethylsulfonic acid, the glycoside reaction can obtain the required glycoside products with high yield (Table 2) Gold catalyst activated glycosylalkynate to form normal glycosides or orthoesters, leaving group to form stable 2-pyranone by-products Among them, the protoester formed in the reaction can be converted into normal glycosides under the catalysis of trifluoromethylsulfonic acid Table 2 Optimization of conditions for glycosylalkynate donor glycosidization (source: org Lett.) after determining the optimal conditions, the author inspected the universality of the reaction (Figure 1) The results show that the substrate of this method is very suitable for a wide range of applications No matter the glycoalkynate donor of disarmed with low activity or the glycoalkynate donor of armed with high activity can react with different types of glycoreceptor to obtain corresponding (1 → 6) -, (1 → 3) - and (1 → 4) - linked disaccharides with high yield For the donor with O-group participation, the reaction results in a single configuration product; for the donor without O-group participation, the reaction generally results in a mixture of α / β configuration Fig 1 Study on the application scope of substrate (source: org Lett.) considering that glycosylalkynate donor can be obtained from stable glycosyl (z) - 3-iodoacrylate intermediate, two oligosaccharides (Fig 2) have been synthesized by the author using the latent activation strategy, which proves the effectiveness of glycosylalkynate donor in the latent activation strategy Fig 2 Synthesis of oligosaccharides by lurking activation strategy (source: org Lett.) orthogonal one pot strategy can avoid the separation and purification of intermediates, greatly simplify the steps of sugar synthesis, and realize the rapid assembly of oligosaccharides Using three different types of donors (trichloroacetimide, alkynate and glucosinolate) and using multiple orthogonal one pot strategy, the target tetrasaccharide was synthesized rapidly and efficiently (Fig 3) Fig 3 Synthesis of target tetrasaccharide by orthogonal one pot method (source: org Lett.) in order to prove the synthesis efficiency of the current glycosylalkynate donor glycosidization method, the author synthesized tetrasaccharide antigen with high immunogenicity on the surface of Streptococcus pneumoniae type 3 (Fig 4) The synthesis confirmed the high efficiency of glycosylalkynate donor for the construction of glycosidic bond in the antigen, especially in the [2 + 2] glycosidization reaction (yield of 88%) which was far superior to the [2 + 2] glycosidization reaction (yield of 54%) reported in literature Fig 4 Synthesis of tetrasaccharide antigen on the surface of Streptococcus pneumoniae type 3 (source: org Lett.) in order to further highlight the practicability of this method, based on glycosylalkynate donor and glucosinolate donor, the authors synthesized α - (1 → 6) - linked mann32 glycoskeleton by 5 times of glycosidization reaction with high aggregation By installing a five carbon link arm on the reducing end of the 32 sugar, and then deprotecting it completely, the target mannose 32 sugar was successfully obtained, which laid a foundation for the study of its potential biological activity Figure 5 High concentration synthesis of mannose 32 (source: org Lett.) Summary: Professor Yang You's research group has invented a simple and multi-purpose gold catalyzed glycosidization of glycosylalkynate donor This method has the advantages of simple donor structure, stable property, high atomic economy, flexible preparation method and wide substrate applicability It has been used in the synthesis of oligosaccharides based on the strategy of latency activation and multiple orthogonal one pot method, and in the synthesis of related oligosaccharide antigens and polysaccharides It is expected to be widely used in the synthesis of glycans and glycoconjugates The research results were recently published in organic letters (DOI: 10.1021 / ACS Orglett 9b03851) Li Xiaona, a doctoral student, is the first author of the paper, and Professor Yang you is the corresponding author The above research work has been supported by the National Natural Science Foundation, the national "thousand talents plan" youth project and the special fund for basic scientific research business fees of central universities Today, people and scientific research have been paid more and more attention to in the economic life
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