A stereoselective Koenigs–Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea‐mediated hydrogen‐bond activation and subsequent glycosylation ...with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low α‐stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri‐(2,4,6‐trimethoxyphenyl)phosphine (TTMPP).
Sugar, sugar: Stereoselective Koenigs–Knorr glycosylation under urea catalysis is described. This method is characterized by urea‐mediated hydrogen‐bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases, and the α‐stereoselectivity when using perbenzylated glucosyl donors is greatly improved by the addition of TTMPP.
Cancer is still one of the most serious threats to human worldwide. Aberrant patterns of glycosylation on the surface of cancer cells, which are correlated with various cancer development stages, can ...differentiate the abnormal tissues from the healthy ones. Therefore, tumor‐associated carbohydrate antigens (TACAs) represent the desired targets for cancer immunotherapy. However, these carbohydrate antigens may not able to evoke powerful immune response to combat with cancer for their poor immunogenicity and immunotolerance. Different approaches have been developed to address these problems. In this review, we want to summarize the latest advances in TACAs based anticancer vaccines.
Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential ...to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency. So far, assembly of long carbohydrate chains remains one of the most challenging tasks for synthetic chemists. Here we describe a highly efficient assembly of a 92-mer polysaccharide by the preactivation-based one-pot glycosylation protocol. Several linear and branched oligosaccharide/polysaccharide fragments ranging from 5-mer to 31-mer in length have been rapidly constructed in one-pot manner, which enables the first total synthesis of a biologically important mycobacterial arabinogalactan through a highly convergent 31+31+30 coupling reaction. Our results show that the preactivation-based one-pot glycosylation protocol may provide access to the construction of long and complicated carbohydrate chains.
Conspectus Carbohydrates are called the third chain of life. Carbohydrates participate in many important biochemical functions in living species, and the biological information carried by them is ...several orders of magnitude larger than that of nucleic acids and proteins. However, due to the intrinsic complexity and heterogeneity of carbohydrate structures, furnishing pure and structurally well-defined glycans for functional studies is a formidable task, especially for homogeneous large-size glycans. To address this issue, we have developed a donor preactivation-based one-pot glycosylation strategy enabling multiple sequential glycosylations in a single reaction vessel. The donor preactivation-based one-pot glycosylation refers to the strategy in which the glycosyl donor is activated in the absence of a glycosyl acceptor to generate a reactive intermediate. Subsequently, the glycosyl acceptor with the same anomeric leaving group is added, leading to a glycosyl coupling reaction, which is then iterated to rapidly achieve the desired glycan in the same reactor. The advantages of this strategy include the following: (1) unique chemoselectivity is obtained after preactivation; (2) it is independent of the reactivity of glycosyl donors; (3) multiple-step glycosylations are enabled without the need for intermediate purification; (4) only stoichiometric building blocks are required without complex protecting group manipulations. Using this protocol, a range of glycans including tumor-associated carbohydrate antigens, various glycosaminoglycans, complex N-glycans, and diverse bacterial glycans have been synthesized manually. Gratifyingly, the synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units has been achieved, which created a precedent in the field of polysaccharide synthesis. Recently, the synthesis of a highly branched arabinogalactan from traditional Chinese medicine featuring 140 monosaccharide units has been also accomplished to evaluate its anti-pancreatic-cancer activity. In the spirit of green and sustainable chemistry, this strategy can also be applied to light-driven glycosylation reactions, where either UV or visible light can be used for the activation of glycosyl donors. Automated synthesis is an advanced approach to the construction of complex glycans. Based on the two preactivation modes (general promoter activation mode and light-induced activation mode), a universal and highly efficient automated solution-phase synthesizer was further developed to drive glycan assembly from manual to automated synthesis. Using this synthesizer, a library of oligosaccharides covering various glycoforms and glycosidic linkages was assembled rapidly, either in a general promoter-activation mode or in a light-induced-activation mode. The automated synthesis of a fully protected fondaparinux pentasaccharide was realized on a gram scale. Furthermore, the automated synthesis of large-size polysaccharides was performed, allowing the assembly of arabinans up to an astonishing 1080-mer using the automated multiplicative synthesis strategy, taking glycan synthesis to a new height far beyond the synthesis of nucleic acids (up to 200-mer) and proteins (up to 472-mer).
We report a novel and highly stereoselective electro‐2‐deoxyglycosylation from glycals. This method features excellent stereoselectivity, scope, and functional‐group tolerance. This process can also ...be applied to the modification of a wide range of natural products and drugs. Furthermore, a scalable synthesis of glycosylated podophyllotoxin and a one‐pot trisaccharide synthesis through iterative electroglycosylations were achieved.
Sweet dreams are made of this: A highly stereoselective electro‐2‐deoxyglycosylation from glycals was developed. This method features excellent stereoselectivity, scope, and functional‐group tolerance, and can also be applied to the modification of a wide range of natural products and drugs. Furthermore, a scalable synthesis of glycosylated podophyllotoxin and a one‐pot trisaccharide synthesis through iterative electroglycosylations were achieved.
A large quantity of polysaccharide‐derived conjugate vaccines have been developed to combat various pathogenic infections. Another prominent polysaccharide, heparin, is listed as an essential drug by ...the World Health Organization (WHO) to treat thrombus. One of their common problems is that they all derive from natural polysaccharides. Specifically, capsular polysaccharides are mainly obtained from bacterial fermentation and unfractionated heparin is extracted from animal tissues such as porcine mucosa. The quality of natural polysaccharides is inconsistent and traces of contamination would cause a disaster. By contrast, the use of chemical or chemoenzymatic methods could provide structurally homogeneous and quality‐controlled glycans. To date, large numbers of polysaccharide fragments and their analogues have been synthesized and evaluated. Some of them even showed comparable activities to their corresponding natural polysaccharides. Here, the latest advances in these synthetic glycan analogues ranging from carbohydrate‐based vaccines, heparin‐related therapeutics and glycomimetics of polysaccharides are summarized.
One common problem of polysaccharide conjugate vaccines and heparin is that natural polysaccharides are structurally heterogeneous and not quality controlled. As an alternative, synthetic glycan conjugates and heparin‐related anticoagulants could provide structurally defined and quality‐consistent molecules. In the future, it may be possible to use synthetic glycans and glycomimetics to replace natural polysaccharides.
Carbohydrates have gained a lot of appreciation in the past few decades due to their important roles in numerous biological events. Acquiring a structurally well‐defined carbohydrate compound is ...essential for the understanding of its functions. Although some innovative methods have been developed for the synthesis of complex oligosaccharides, glycan synthesis is in general still a time‐consuming and difficult work. Herein, we will introduce the preactivation‐based glycosylation strategy, which is an efficient protocol independent of the reactivity of glycosyl donor. This review will focus on summarizing the versatile applications of preactivation strategy in stereoselective glycosylation and one‐pot assembly of biologically important oligosaccharides and even polysaccharides.
What is the most favorite and original chemistry developed in your research group?
Preactivation‐based one‐pot glycosylation strategy and applications.
How do you get into this specific field? Could you please share some experiences with our readers?
I got into this field when I was a research associate in 1996. My supervisor, Prof. Chi‐Huey Wong, gave me a research topic for synthesis of oligosaccharide libraries. At that moment, as a beginner, I did not know too much carbohydrate chemistry, just to learn and to do it. The importance and challenge of carbohydrates attracted me.
What is the most important personality for scientific research?
Curiosity, passion, and creative thinking.
How do you supervise your students?
In my opinion, before the graduate students start a specific project, their experimental skills need to be well trained. During the period of graduate studies, the enhancement of abilities to analyze problems and to solve problems is very important. The graduate students should always keep an eye on the unusual experimental phenomena.
What's your hobbies?
Reading history books.
What is your favorite journals?
The journals publishing the latest research works in chemistry and medical science.
Saccharides are polyhydroxy compounds, and their synthesis requires complex protecting group manipulations. Protecting groups are usually used to temporarily mask a functional group which may ...interfere with a certain reaction, but protecting groups in carbohydrate chemistry do more than protecting groups usually do. Particularly, protecting groups can participate in reactions directly or indirectly, thus affecting the stereochemical outcomes, which is important for synthesis of oligosaccharides. Herein we present an overview of recent advances in protecting groups influencing stereoselectivity in glycosylation reactions, including participating protecting groups, and conformation-constraining protecting groups in general.
A general approach to the synthesis of diverse heteroaryl-C-Δ1,2-glycosides has been developed by employing the Pd(OAc)2/CuI cocatalyzed direct cross-coupling of five-membered nitrogen heterocycles ...with 1-iodoglycals in a C–H activation manner. Using this method, 27 examples of heteroaryl-C-Δ1,2-glycosides, containing indoles, thiazoles, benzothiazoles, imidazoles, benzimidazoles, and benzoxazoles as aglycones were obtained in 43–99% yield.
The photoinitiated intramolecular hydroetherification of alkenols has been used to form C−O bonds, but the intermolecular hydroetherification of alkenes with alcohols remains an unsolved challenge. ...We herein report the visible‐light‐promoted 2‐deoxyglycosylation of alcohols with glycals. The glycosylation reaction was completed within 2 min in a high quantum yield (ϕ=28.6). This method was suitable for a wide array of substrates and displayed good reaction yields and excellent stereoselectivity. The value of this protocol was further demonstrated by the iterative synthesis of 2‐deoxyglycans with α‐2‐deoxyglycosidic linkages up to a 20‐mer in length and digoxin with β‐2‐deoxyglycosidic linkages. Mechanistic studies indicated that this reaction involved a glycosyl radical cation intermediate and a photoinitiated chain process.
A fast photoglycosylation is reported that proceeds through a bromide‐based hydrogen species and electron transfer process. The value of this protocol was well demonstrated by the iterative synthesis of oligosaccharides on a gram scale as well as digoxin and a 20‐mer deoxyglycan in good yields and with excellent stereoselectivity.