Glycosyl donors in “unusual” conformations – influence on reactivity and selectivity (original) (raw)
Organic Letters, 2019
Stereo-and regio-selective formation of glycosidic linkages are a challenging topic in oligosaccharide syntheses. The stereoselective construction of 1,2-trans-glycosides generally involves neighboring group participation, which is less successful when synthesizing -1,3-linked oligosaccharides. The combined steric effect of a 2-O-substituent and an aglycon moiety in acceptors increases the efficiency of glycosylation via neighboring group participation. This steric effect was reduced by using vicinal polyol acceptors and was demonstrated in the synthesis of 1,3-linked branched oligosaccharides. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: Detailed experimental procedures, characterization, and 1 H and 13 C spectra of new compounds The Supporting Information is available free of charge on the ACS Publications website. brief description (file type, i.e., PDF) brief description (file type, i.e., PDF)
Organic & biomolecular chemistry, 2017
A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.
Glycosyl Hydrolases and Glycosyltransferases in the Synthesis of Oligosaccharides
Current Organic Chemistry, 2006
Glycobiology and related disciplines have received an enormous interest in recent years as they shed new light on the functional roles of carbohydrates in biological events leading to the understanding of mechanisms of important pathologies and to the development of new therapeutics. Although carbohydrate can be isolated from natural sources, the synthetic strategy plays its own role allowing access to larger quantities of structurally defined material and entry to analogs of naturally occurring structures. Nowadays, the bottleneck in this field is represented by some limitations of the potential of carbohydrate containing molecules because their complex structures make classical chemical synthesis very difficult.
Superarming of Glycosyl Donors by Combined Neighboring and Conformational Effects
Organic Letters, 2013
A novel glycosyl donor that combines the concepts of both conformational and electronic superarming has been synthesized. The reactivity and selectivity of the donor has been tested in competition experiments. Traditionally oligosaccharide synthesis relies on protective group manipulations and the use of orthogonal glycosylation methods, such as different types of glycosyl donors. Due to the increased interest in biologically relevant oligosaccharides the development of new methodologies have been impressive during the last couple of decades and paved the way for more efficient synthesis. 1,2 These developments include, but are not limited to, one-pot protection 3 and glycosylation strategies, 4,5 polymer-supported 6 and automated synthesis, 7,8 ionic liquid supported, 9,10 fluorous tag assisted, 11,12 surface-tethered (STICS), 13 and HPLCassisted syntheses. 14 The control of the glycosyl donor's reactivity belongs to the tools available for improving oligosaccharide synthesis. The armed-disarmed concept was introduced by the group of Fraser-Reid, 15 and utilizes selective activation of one donor over another with the same anomeric leaving group. The reactivity of the donor relies on the protective groups used; more electron-withdrawing groups reduce (disarm) the donor reactivity and vice versa. Glycosyl donor A1 is armed (benzylated) whereas A2 is disarmed (more electronwithdrawing protective groups) and acts as the glycosyl acceptor (Scheme 1A). 15,16 With the insight into manipulation of reactivity by protective groups, new methodologies for oligosaccharide have been developed, one example is "one-pot" oligosaccharide strategies,
Towards the 21st century - the emerging importance of oligosaccharide synthesis
Pure and Applied Chemistry, 1997
Recent progress in glycobiology has made the synthesis of oligosaccharides of prime importance for biomedical studies. Two such syntheses are described in order to illustrate our current research in this area. The first concerns the synthesis of oligosaccharides corresponding to the capsular polysaccharide of the yeast Cryptococcos neoformans, the second is the synthesis of a highly branched octasaccharide corresponding to the cell surface lipopolysaccharide of the Gram-negative bacterium Moraxella catarrhalis. In both syntheses extensive use was made of thioglycosides as glycosyl donors or as glycosyl donor precursors.
Isopropenyl glycosides and congeners as novel classes of glycosyl donors: theme and variations
Journal of the American Chemical Society, 1992
Isopropenyl glycosides (Le., 10 and 11) have been synthesized in high yields by reacting the corresponding anomeric acetates with the Tebbe reagent. These compounds undergo glycosylation with primary or secondary carbohydrate alcohols in the presence of trimethylsilyl triflate or boron trifluoride etherate, probably via a mixed acetal glycoside intermediate. On the basis of this principle, a quite efficient glycosylation of monosaccharide hemiacetal donors (i.e., 1, 7, and 9 ) with acceptors bearing an isopropenyl ether function at a primary or secondary position (Le., 18 and 21) has been developed. Also investigated were the glycosylating properties of isopropenyl glucosyl and galactosyl carbonates (Le., 12-15), easily prepared from the corresponding hemiacetals, toward sugar alcohols. In each case, the @-selective synthesis of disaccharides from donors having nonparticipating groups at C-2 was ensured by the use of acetonitrile, at low temperature, as the solvent. Simple, efficient, and selective synthesis of oligosaccharides is a central problem in carbohydrate chemistry.] The so-called Koenigs-Knorr glycosylation, based on the use2 of glycosyl halides as glycosyl donors, has by and large been the essential synthesis for a very long period of time. Recently a lot of work has been devoted to the search for a 'non-Koenigs-Knorr" activation of the anomeric center. The trichloroacetimidate glycosylation3-a useful modification of the imidate procedure4 -has been frequently used for the practical, selective syntheses of complex oligosaccharides and glycoconjugates. Thioglycosides are also attracting considerable attention along these lines5 In the same respect, the glycosylating properties of the alkenyl glycosides have been explored. The pent-4-enyl glycosides6 are currently used as glycosyl donors. Much less studied is the behavior of the alk-1-enyl glycosides, molecules which should be good candidates for the generation of anomeric oxycarbenium ions. Vinyl glycopyranosides' are known compounds, but p r o p 1 -enyl glycosides are the most common members of the alk-1-enyl family. The widespread use of prop-2-enyl (allyl) ether as a protecting group originates from its easy conversions into a propl-enyl ether which, in the presence of various reagents,8 regenerates the hydroxyl group. It has been shown9 that the mercury(I1) chloride induced cyclization of p r o p 1 -enyl @-glycosides provided a simple and efficient procedure for the preparation of oxazoline derivatives. (1) (a) Paulsen, H.
Trends in Glycoscience and Glycotechnology, 2018
The glycosylation on asparagine residues is one of the ubiquitous protein modifications occurring in the three domains of life. An oligosaccharide chain is preassembled on a lipid-phospho carrier, which is referred to as lipid-linked oligosaccharide (LLO), and transferred to asparagine residues in polypeptide chains by the action of a membrane-bound enzyme, oligosaccharyltransferase. The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol-diphosphate-oligosaccharide in Eukarya, and polyprenol-diphosphate-oligosaccharide in Eubacteria. The oligosaccharide donor of an archaeal species was reported as dolicholmonophosphate-oligosaccharide. Thus, the difference in the number of phosphate groups aroused interest in whether the use of the monophosphate type donor is widespread in the domain Archaea. In this study, we selected four archaeal species to widely sample the domain Archaea. We used normal-phase liquid chromatography to purify the LLO from cultured archaeal cells and performed ESI-MS analysis to determine the chemical structure of the lipid-phospho part. We found that two euryarchaeal oligosaccharide donors of more ancient origin were a dolichol-monophosphate type, whereas the two crenarchaeal oligosaccharide donors of closer origin to Eukarya were a dolichol-diphosphate type. The present comparative study provides a new insight into the evolution of the oligosaccharide donor in the N-glycosylation system.
Opportunities and challenges in synthetic oligosaccharide and glycoconjugate research
Nature Chemistry, 2009
semi-synthetic over-sulfated chondroitin sulfate, which is a popular shellfish-derived oral supplement for arthritis. There is a growing body of literature indicating that glycosylaminoglycans (GAGs), such as heparin and heparan sulfate, can have profound physiological effects on lipid transport and adsorption, cell growth and migration and development 5. Alterations in GAG expression has been associated with cancer and, for example, significant changes in the structure of GAGs has been reported in the stroma surrounding tumours, which is important for tumour growth and invasion. GAGs also have important neurobiological functions and examples include neuroepithelial growth and differentiation, neurite outgrowth, nerve regeneration, axonal guidance and branching, deposition of amyloidotic plaques in Alzheimer's disease, and astrocyte proliferation 37. It is to be expected that a b c d synthetic analogues of heparin may find application in the treatment of several neurodiseases, cancer and infection 33,34,37-42. Carbohydrate-based prophylactic and therapeutic vaccines. Synthetic oligosaccharide epitopes offer promising possibilities for the development of vaccines for the prevention of infectious diseases such as Haemophilus influenzae type b, HIV, Plasmodium falciparum, Vibrio cholerae, Cryptococcus neoformans, Streptococcus pneumoniae, Shiga toxin, Neisseria meningitides, Bacillus anthracis and Candida albicans 17,18,43,44. Natural polysaccharides conjugated to carrier proteins have been successfully developed as human vaccines, however, their use is associated with problems such as the destruction of vital immuno-dominant features during the chemical conjugation to a carrier protein 17. Furthermore,