Emerging Trends in Glycoscience

Carbohydrates are the most abundant and one of the most important biomolecules known for their widespread applications in chemistry, biology, and medicine. The main objective of this thematic issue on ‘Emerging Trends in Glycoscience’ is to present comprehensive information about the growing importance of synthetic carbohydrate chemistry. Their remarkable functions for the survival of the living system have been well documented in the literature for a long back. Due to their pivotal role in several important biological processes, in particular energy storage, transport, modulation of protein function, intercellular adhesion, malignant transformation, signal transduction, viral and bacterial cell surface recognition, inflammation, immune response, metastasis, fertilization, microbial infections, etc., there is an increasing demand for carbohydrate-containing molecules for their complete chemical, biochemical and pharmacological investigations. In addition to their easy accessibility, high functionality and chiral pool properties, carbohydrates have a few other fascinating structural features that further enhance their utility and have attracted chemists and biologists worldwide to exploit these properties over the past decades. This special issue examines the remarkable developments in the chemical or enzymatic synthesis of carbohydrates and their chemical and therapeutic applications in biology and medicine. Therefore, our primary interest is to welcome the contributions from the experts working on new aspects of carbohydrates including their synthesis and application in catalysis and medicines. The topics covered in this special issue are broad and aim to present an advanced aspect of carbohydrate-based molecular scaffolding, followed by a detailed discussion of their importance in chemical biology to catalysis and materials science to medicinal chemistry.

This thematic issue is divided into a total of 22 excellent contributions (five reviews and 17 original manuscripts) which are based on the underlying ideas of the different aspects of synthetic carbohydrate chemistry. Several leading experts, who are very active in this field, have contributed to this special issue and I am grateful to them for their excellent contribution. We hope that the contributions will greatly help the readers to have a better understanding of the current state of chemistry and biology of carbohydrates required to formulate the carbohydrate systems to be an extremely valuable scaffold for the successful development of carbohydrate-based molecules of pharmacological importance.

The development of stereoselective route for easy access to the biologically relevant diverse C-glycosides has long been of paramount importance. The thematic issue begins with the contribution of Nahide-Annapragada-Bandichhor (DOI: 10.1055/s-0042-1751524) on the chemistry of Gliflozins, a class of C-glycosides that inhibit the function of SGLT stand out as highly effective chemotherapeutic agents for the effective management of type 2 diabetes. The authors presented a comprehensive overview of the synthetic advancements with challenges and future perspectives of the gliflozin-based potential anti-diabetes drugs such as Canagliflozin, Dapagliflozin, Ipragliflozin, Empagliflozin, Luseogliflozin, Tofogliflozin, Ertugliflozin, Sotagliflozin, Licogliflozin, Remogliflozin, Henagliflozin, Bexagliflozin, Janagliflozin, Velagliflozin, Sergliflozin Etabonate, and Enavogliflozin. Furthermore, Mukherjee-Kundu and co-workers (DOI: 10.1055/a-2223-1303) presented an updated overview of the synthesis of C-glycosides along with their emerging applications in the development of bioactive natural products and potent drug candidates via carbon-Ferrier, intramolecular Cope, Claisen rearrangements, and some coupling reactions from 1,2-glycal scaffolds.

Glycals are widely used to produce glycosyl anions or oxocarbenium cations for the anomeric C–C bond synthesis via transition-metal-catalyzed coupling processes or C–C nucleophile attack. The Achanta-Bandichhor group presented a comprehensive overview of the predictive models to address the stereochemical aspects of C-glycosylation of pyranosides and furanosides via Lewis acid-promoted six- and five-membered ring oxocarbenium ions with allyltrimethylsilane nucleophile, arylalane addition to anhydroglucose, glucal epoxide route, and transition metal-mediated cross-coupling reactions. Also, C-2-formyl glycals have been widely used as valuable chiral building blocks in organic synthesis for easy access to pharmacologically active molecules. Thus, the Prasad group (DOI: 10.1055/a-2066-1659) presented a comprehensive overview of the recent synthetic progress of C-2-formyl glycals and their growing applications for easy access to various chiral supramolecular molecules of remarkable utility in chemistry, biology, and material sciences.

The biological significance of nucleosides, a building block for nucleic acids can be tailored by chemically modifying the five-carbon sugar to influence its sugar pucker. Notably, the spirocyclic scaffold is indispensable in several approved drugs and its inherent three-dimensionality makes as an ideal modification to influence the sugar pucker and biological properties of nucleosides. Singh and co-workers (DOI: 10.1055/s-0042-1751509) highlight the recent synthetic routes for easy access to various C-1’, C-2’, C-3’, C-4’, and miscellaneous spirocyclic nucleosides with the challenges ahead and future perspectives. Furthermore, Prasad and co-workers (DOI: 10.1055/s-0041-1738440) describe a chemoenzymatic convergent route for the high-yield synthesis of a new class of bicyclic nucleosides corresponding to arabino-configured uracil and thymine bicyclic nucleosides from 1,2,5,6-di-O-isopropylidene-α-d-glucofuranose.

Superarmed glycosyl donors have higher reactivity compared to their perbenzylated armed counterparts. Because of an O-2/O-5 cooperative effect, the 2-O-benzoyl-3,4,6-tri-O-benzyl protection generally resulted in a significantly increased reactivity, where its utilitu for glycan synthesis is well explored. However, the regioselective introduction of the superarming protecting group pattern is rather tedious. The Demchenko group (DOI: 10.1055/a-2183-0175) have addressed this issue and reported a streamlined synthetic route to access a diverse series of superarmed glycosyl donors and exemplified them for the straightforward, high-yield synthesis of well-defined disaccharides by refining of the oxidative thioglycosylation of the respective glycals.

Despite the fluorine-directing effect being a well-explored route to rare l-ido sugars, the Ferro group (DOI: 10.1055/a-2149-4586) demonstrated the behavior of glycosyl radicals towards photo-bromination, which is dependent on the anomeric configuration for the synthesis of α- and β-configured per-O-benzoylated mannopyranosyl fluorides. The methodology reveals the fluorine-directing effect by striking differences in the stereoselectivity observed for the free-radical reductions of the isolated 5-C-bromo sugars.

The Kandasamy group (DOI: 10.1055/a-2179-8669) devised a stereocontrolled high-yielding synthesis of 2-deoxy-α-aryl-C-glycosides through 1,4-conjugate addition of arylboronic acids to the glycal enones derived from d-glucal, d-galactal, and d-rhamnal using PdOAc₂ in the presence of trifluoroacetic acid and 1,10-phenanthroline. Furthermore, the Mandal group (DOI: 10.1055/a-2186-7116) reported a highly stereoselective α-C-glycosylation method of a variety of glycals coupled with allyltrimethylsilane or trimethylsilylphenylacetylene via simultaneous borane activation of the glycal donor using tris(pentafluorophenyl)borane to access high yields of the respective 2,3-unsaturated allyl- and alkynyl-C-glycosides with excellent α-selectivity.

Hussain group (DOI: 10.1055/a-2126-0815) reported a site-selective thioglycosylation of pseudo glycals for access to diverse 1-deoxy-C-2 thioaryl glycosides under Lewis acid catalysis. The substrate scope and the late-stage modifications of several drug candidates are demonstrated. The Panchadhayee­ group (DOI: 10.1055/a-2218-7604) devised a high-yield, short, and efficient protocol for the O-isopropylidene protection of diverse carbohydrates at room temperature by using a sulfonated graphene-promoted mild, recyclable, and sustainable acid catalyst. Furthermore, the use of sustainable catalytic methods for O-glycosylation may provide an effective tool for traditional protocols involving stoichiometric promoters and classical donors. Considering an important facet of glycosylation, Kumar and group (DOI: 10.1055/a-2193-4615) described an efficient FeCl₃-promoted O-glycosylation method through the activation of benchtop stable bifunctional phenylpropiolate glycoside (PPG) donors. The desired O-glycosides were obtained in high yields along with the regeneration of easily separable phenylpropiolic acid and the d-mannose and l-rhamnose-based PPG donors afforded the O-glycosides with remarkable α-anomeric selectivity.

It is difficult to isolate the structurally defined desired oligosaccharides from the natural sources and thus their chemical synthesis by utilizing selective (regio- and stereo-) and high-yield glycosylation steps is very challenging. Misra­ group (DOI: 10.1055/s-0042-1751460) nicely used a convergent [5+3] block glycosylation strategy to develop a high yield of the octasaccharide repeating unit of the K55 capsular polysaccharide of Acinetobacter baumannii BAL_204 strain. Further, the authors (DOI: 10.1055/s-0040-1720095) developed a rapid route for the high-yield synthesis of the hexasaccharide repeating unit corresponding to the capsular polysaccharide of Streptococcus pneumoniae type 7A using [3+2+1] block synthetic strategies. The same group (DOI: 10.1055/s-0042-1751517) also used a stereo- and regioselective [4+2] block glycosylation strategy for the simple synthesis of the hexasaccharide repeating unit of the O-specific polysaccharide of the Providencia alcalifaciens O9:H8 strain.

The development of effective vaccines against APEC O1 is essential due to antibiotic resistance and the potential for severe symptoms in both chickens and humans. To this end, the Takahashi group (DOI: 10.1055/a-2152-0255) successfully developed pentasaccharide repeating units of the O1B and O1C antigens focusing on the O1A, O1B, and O1C antigen structures derived from E. coli O1 lipopolysaccharide (LPS). The O1A-pentasaccharide structure was found to be a promising glycotope candidate for APEC O1.

Interestingly, Zhimeng group (DOI: 10.1055/a-2093-3528) reported a bispecific ARM strategy targeting CD44 and nanobody 7D12 or peptide GE11 targeting EGFR, constructed for cancer immunotherapy. The result verified the dual-targeting ability of CD44 and EGFR of developed complexes and the rhamnose on HACD could recruit anti-Rha antibodies to mediate cytotoxicity against the targeted tumor cells.

The Singh group (DOI: 10.1055/s-0042-1751505) reported an rapid and scalable tool for the diastereoselective synthesis of biologically relevant carbohydrate-containing pyrano[3,2-c]quinolones from Perlin aldehydes and 4-hydroxyquinolones under mild one-pot reaction conditions. The Ram Sagar group (DOI: 10.1055/a-2157-9100) incorporated hybridization of the bioactive heterocyclic scaffolds with biocompatible carbohydrates and developed a high yield of a novel class of potent anticancer glycohybrid imidazo-pyrazoles and imidazo-1,2,3-triazoles in optically pure form via K₂CO₃ mediated coupling of the carbohydrate-derived α-iodo-2,3-dihydro-4H-pyran-4-ones separately with aminopyrazoles and aminotriazoles. The same group (DOI: 10.1055/a-2181-9709) further considered the structure of bioactive aryl glycosides and quinones and explored the synthesis of natural product-inspired naphthoquinone-fused glycohybrids with their improved binding affinity and specificity towards cancer-related protein targets. The enhanced interactions between the resulting glycohybrids and target proteins were also validated by computational docking simulations. Finally, the Tiwari group (DOI: 10.1055/a-2157-9001) exemplified the use of glycosyl 1,2,3-triazole-based pyridinamide as biocompatible ligands for the efficient coupling of N-substituted 2-halobenzamides and active methylene compounds via intermolecular C–C cross-coupling followed by intramolecular cyclization under Cu(I)-catalyzed tandem route to give high yields of biologically relevant dihydrophenanthridinediones and isoquinolinones.

In summary, the collection of excellent reviews and original articles featured in this special issue, by well-known experts in the field, highlights the advances in the growing field of synthetic carbohydrate chemistry. On behalf of Thieme Publishing and myself, I would like to express my sincere gratitude to all the contributing authors, who are eminent scientists actively involved in various aspects of carbohydrate chemistry, for accepting our invitation. We would also like to express our special thanks to all the peer-reviewers for their constructive comments and suggestions, which are necessary to maintain the high standard of the manuscripts. We hope that the articles published in this special issue will be of great interest to the readers and researchers. The outlook for future research on this topic is very promising and this special issue may provide exceptional opportunities to explore an innovative idea for the growing fields of glycoscience useful in academia and industry. Finally, I would like to express my deep sense of appreciation to professor Mark Lautens, Editor-in-Chief, and the entire editorial team associated with Thieme especially Dr. Rohit Bhatia for their timely support in publishing this topic with the high standard of publication maintained in bringing out this special issue on ‘Emerging Trends in Glycoscience’ with ‘SYNTHESIS’.

Prof. Vinod K. Tiwari, PhD

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Publication History

Article published online:
27 February 2024

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