Article
Chemistry, Multidisciplinary
Zhen Wang, Ana Gimeno, Marta G. Lete, Herman S. Overkleeft, Gijsbert A. van der Marel, Fabrizio Chiodo, Jesus Jimenez-Barbero, Jeroen D. C. Codee
Summary: We report the first total synthesis of the Streptococcus pneumoniae serotype 1 (Sp1) oligosaccharide, which is a zwitterionic capsular polysaccharide carrying unstable O-acetyl esters. The synthesis was achieved by assembling trisaccharide building blocks in a highly stereoselective manner, up to the 9-mer level. The structure investigation revealed that the oligomers adopt a right-handed helical structure, with the acetyl esters exposed on the periphery and in close proximity of the neighboring AAT residues.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Catherine Alex, Alexei V. Demchenko
Summary: This paper describes a new method for the direct, highly stereoselective synthesis of glycans containing beta-linked D-mannosaminuronic acid (ManNAcA) residues, including the capsular polysaccharide of Staphylococcus aureus type 8. The method achieves stereocontrol and introduces a way to achieve complete alpha-ManNAcA stereoselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yuanyuan Bai, Xiaohong Yang, Hai Yu, Xi Chen
Summary: Innovation in process development is crucial for the industrial and laboratory production of organic compounds, such as HMOs, through biocatalysis. A substrate and process engineering strategy called MSOPME design allows for efficient synthesis of HMOs, including long-chain oligosaccharides, without the need for isolation of intermediate products. The method can be scaled up for large-scale synthesis and automation.
Article
Chemistry, Multidisciplinary
Xiaona Li, Cristina Di Carluccio, He Miao, Lvfeng Zhang, Jintao Shang, Antonio Molinaro, Peng Xu, Alba Silipo, Biao Yu, You Yang
Summary: We report a promoter-controlled cycloglycosylation approach for the synthesis of cyclic α-(1→6)-linked mannosides up to a length of 32 units. The method relies on the role of a gold(I) complex in the proper preorganization of the ultra-large cyclic transition state. NMR experiments and a computational study revealed that the cyclic 2-mer, 4-mer, 8-mer, 16-mer, and 32-mer mannosides adopted different conformational states and shapes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Sooyeon Moon, Sourav Chatterjee, Peter H. Seeberger, Kerry Gilmore
Summary: By quantifying the steric and electronic contributions of all chemical reagents and solvents through quantum mechanical calculations, a random forest algorithm was trained to accurately predict the stereoselective outcome of glycosylations. The model accurately predicts stereoselectivities for unseen nucleophiles, electrophiles, acid catalyst, and solvents across a wide temperature range, and was experimentally validated on a microreactor platform. This model helps identify novel ways to control glycosylation stereoselectivity and accurately predicts previously unknown means of stereocontrol.
Article
Chemistry, Multidisciplinary
Chaoyu Hu, Shengjie Wu, Fei He, Deqin Cai, Zhuojia Xu, Wenjing Ma, Yating Liu, Bangguo Wei, Tiehai Li, Kan Ding
Summary: Bioactive polysaccharides are potential target molecules for drug development, but the synthesis of branched complex polysaccharides with well-defined structures is challenging. In this study, a highly branched heptadecasaccharide moiety of a native bioactive polysaccharide from Carthamus tinctorius L. was efficiently synthesized, and its biological activity in targeting galectin-3 and inhibiting pancreatic cancer cell growth was demonstrated.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Samira Escopy, Yashapal Singh, Keith J. Stine, Alexei V. Demchenko
Summary: As the 21st century unfolds with rapid changes, new challenges have arisen in research and development. This article introduces a solution phase batch synthesis method based on the HPLC platform, which enables sequential synthesis of multiple oligosaccharides and automates the process.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Ao Sun, Zipeng Li, Yuchao Wang, Shuai Meng, Xiao Zhang, Xiangbao Meng, Shuchun Li, Zhongtang Li, Zhongjun Li
Summary: This study presents an indirect method for the stereoselective synthesis of alpha-Kdo glycosides. The method utilizes a C3-p-tolylthio-substituted Kdo phosphite donor to achieve enhanced reactivity and complete alpha-stereocontrol. Various Kdo alpha-glycosides were successfully synthesized using this method. The orthogonality of the phosphite donor and thioglycoside donor was demonstrated through the one-pot synthesis of a trisaccharide. Furthermore, an efficient total synthesis route for a challenging 4,5-branched Kdo trisaccharide was highlighted. The high reactivity of the approach was further demonstrated by the synthesis of a highly crowded 4,5,7,8-branched Kdo pentasaccharide.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Bijoyananda Mishra, Sujit Manmode, Gulab Walke, Saptashwa Chakraborty, Mahesh Neralkar, Srinivas Hotha
Summary: The chemical synthesis of complex oligosaccharides, especially those with hyper-branched structures and specific glycosidic bonds, is a challenging task due to factors such as reactivity of glycosyl donors and acceptors, and proper tuning of solvent/temperature/activator. In this study, a semi-conserved hyper-branched core tetrasaccharide motif was successfully synthesized from chloroviruses, involving a thorough study of various factors to achieve a stereoselective galactopyranosidic linkage.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Mariya Novakova, Anupama Das, Catherine Alex, Alexei V. V. Demchenko
Summary: This study presents a streamlined synthesis of a rare sugar D-altrosamine and investigates the glycosylation of different glycosyl acceptors using differentially protected altrosamine donors. High facial stereoselectivity is achieved through the H-bond-mediated aglycone delivery (HAD) pathway with 3-O-picoloyl donors and reactive glycosyl acceptors. In contrast, glycosidations with altrosamine donors equipped with the 3-O-benzoyl group show poor stereoselectivity.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Organic
Ganesh Shrestha, Matteo Panza, Yashapal Singh, Keith J. Stine, Alexei V. Demchenko
Summary: In this study, the activation process of N-alkylated SInR derivatives was investigated by NMR, leading to the discovery of different activation pathways for SIn and SInR derivatives. The orthogonality between SInR leaving groups and thioglycosides, as well as the selective activation of thioimidates over SInR glycosides, were also examined.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yasmeen Bakhatan, Israel Alshanski, Chieh-Kai Chan, Wei-Chih Lo, Po-Wei Lu, Pin-Hsuan Liao, Cheng-Chung Wang, Mattan Hurevich
Summary: Solid-phase synthesis is the main method for preparing biological oligomers. Accelerated solid-phase synthesis is crucial for chemical biology but is not easy for oligosaccharide synthesis. High shear stirring is a new approach to accelerate solid-phase synthesis by improving mixing efficiency. In this study, we used high shear mixing to perform diffusion-dependent glycosylation and completed full glycosylation cycles in minutes.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Food Science & Technology
Meijun Zeng, Ning Li, Theresa Astmann, Jee-Hwan Oh, Jan-Peter van Pijkeren, Xuejun Pan
Summary: A facile chemical process was developed to synthesize glucose-based short-chain oligosaccharides (GlcOS) as potential prebiotics. The GlcOS were successfully synthesized with a high yield of 83% using concentrated sulfuric acid (60-92%) as the reaction medium. In vitro fermentation experiments showed that the synthesized GlcOS could serve as a carbon source for bacterial growth, and their promotion effect was comparable to three commercial prebiotic IMOs.
FOOD RESEARCH INTERNATIONAL
(2023)
Article
Chemistry, Organic
Siyu Li, Yujuan Wang, Lei Zhong, Siyu Wang, Zhengli Liu, Yuanwei Dai, Yun He, Zhang Feng
Summary: In this study, we disclosed an efficient method for the stereospecific synthesis of 1-thioglycosides via a boron-promoted reductive deoxygenation coupling reaction from readily accessible sulfonyl chlorides and glycosyl bromides. Our protocol features mild conditions, excellent functional group tolerance, and stereoselectivity. The translational potential of this metal-free approach is demonstrated by the late-stage glycodiversification of natural products and drug molecules.
Article
Chemistry, Applied
Zuzana Meszaros, Lucie Petraskova, Natalia Kulik, Helena Pelantova, Pavla Bojarova, Vladimir Kren, Kristyna Slamova
Summary: Fungal beta-N-acetylhexosaminidases are important tools for the synthesis of natural and modified oligosaccharides and glycoconjugates. In this study, the enzyme from Aspergillus oryzae was engineered to shift its reaction from hydrolysis to transglycosylation. Nine mutant variants of the enzyme were designed and tested, and one variant (V306W/Y445N AoHex) showed superior transglycosidase activity with a transglycosylation-to-hydrolysis ratio greater than 110, which is unique among similar mutants.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Ganesh Shrestha, Gustavo A. Kashiwagi, Keith J. Stine, Alexei Demchenko
Summary: The article presented an improved synthesis method for a common 3-OH glycosyl acceptor, utilizing Koto's selective benzylation protocol followed by acylation-purification-deacylation sequence. Despite involvingadditional manipulations, this approach offers consistent results and is superior to other indirect strategies. In addition to obtaining 3-OH acceptor, a minor quantity of 4-OH acceptor was also obtained.
CARBOHYDRATE RESEARCH
(2022)
Review
Chemistry, Multidisciplinary
Samira Escopy, Alexei Demchenko
Summary: This review highlights recent methods for thioglycoside activation that rely on transition metal catalysis. The requirement for toxic and/or large access of activators needed for common glycosylations with thioglycosides is a notable drawback, driving the goal of finding non-toxic reagents in synthetic studies.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Catherine Alex, Alexei V. Demchenko
Summary: This paper describes a new method for the direct, highly stereoselective synthesis of glycans containing beta-linked D-mannosaminuronic acid (ManNAcA) residues, including the capsular polysaccharide of Staphylococcus aureus type 8. The method achieves stereocontrol and introduces a way to achieve complete alpha-ManNAcA stereoselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Immunology
Michael P. Mannino, Gerald W. Hart
Summary: The addition of N-acetyl glucosamine to serine/threonine residues, known as O-GlcNAcylation, plays a crucial role in cellular processes and its dysregulation is associated with various diseases. O-GlcNAc interacts with other post-translational modifications, affecting gene expression, protein localization, and stability. This review discusses the roles of O-GlcNAc and its impact on the immune system.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Samira Escopy, Yashapal Singh, Keith J. Stine, Alexei V. Demchenko
Summary: As the 21st century unfolds with rapid changes, new challenges have arisen in research and development. This article introduces a solution phase batch synthesis method based on the HPLC platform, which enables sequential synthesis of multiple oligosaccharides and automates the process.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Ganesh Shrestha, Matteo Panza, Yashapal Singh, Keith J. Stine, Alexei V. Demchenko
Summary: In this study, the activation process of N-alkylated SInR derivatives was investigated by NMR, leading to the discovery of different activation pathways for SIn and SInR derivatives. The orthogonality between SInR leaving groups and thioglycosides, as well as the selective activation of thioimidates over SInR glycosides, were also examined.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Olivia Slater, Kapur B. Dhami, Ganesh Shrestha, Maria Kontoyianni, Michael R. Nichols, Alexei V. Demchenko
Summary: This study reports the development of a new Lipid-A analogue lacking a disaccharide core but still exhibiting potent antagonistic activity against LPS-induced inflammation. Computational, synthetic, and biological studies revealed new structural determinants of these simplified analogues.
ACS INFECTIOUS DISEASES
(2022)
Review
Chemistry, Multidisciplinary
Yashapal Singh, Scott A. Geringer, Alexei V. Demchenko
Summary: Advances in synthetic carbohydrate chemistry have improved access to common glycans, but challenges remain. Glycosyl halides play a crucial role in glycosylation.
Article
Chemistry, Organic
Scott A. Geringer, Gustavo A. Kashiwagi, Alexei V. Demchenko
Summary: The reverse orthogonal strategy, using orthogonal protecting groups that can be removed during glycosylation, offers a new approach to simplify glycan assembly. New combinations of orthogonal leaving and protecting groups have been discovered, improving the efficiency of this strategy.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Materials Science, Multidisciplinary
Palak Sondhi, Dhanbir Lingden, Jay K. K. Bhattarai, Alexei V. V. Demchenko, Keith J. J. Stine
Summary: Nanoporous gold (np-Au) has unique properties that make it attractive for therapeutic applications, including high surface area-to-volume ratio, tunable shape and size, ability to interact with organic molecules including drugs, and biocompatibility. The photothermal effect of np-Au nanostructures can be utilized for controlled drug release and local heating for cancer cell destruction. Despite its enormous potential, research on the therapeutical use of np-Au is still in its early stages.
Article
Chemistry, Multidisciplinary
Ashley Dent, Samira Escopy, Alexei V. Demchenko
Summary: This study presents a novel method for activating thioglycosides without using a glycosyl halide intermediate. It utilizes a combination of a silver salt, an acid additive, and molecular iodine. The enhanced stereocontrol is achieved through the H-bond mediated aglycone delivery (HAD) method, and the extended trisaccharide synthesis is achieved via a series of deprotection and glycosylation steps.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Nicholas Forsythe, Leah Liu, Gustavo A. Kashiwagi, Alexei V. Demchenko
Summary: A novel method for activating thioglycosides and thioimidates using benzyl trichloroacetimidate in the presence of catalytic triflic acid is reported. Excellent yields were achieved with reactive substrates, but the efficiency of reactions with unreactive glycosyl donors and/or acceptors was modest.
CARBOHYDRATE RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Yashapal Singh, Samira Escopy, Melanie Shadrick, Mithila D. Bandara, Keith J. Stine, Alexei V. Demchenko
Summary: Human milk oligosaccharides (HMO) are an active area of research in glycoscience and nutrition due to their involvement in infant development and potential disease prevention. This study reports the chemical synthesis of two core hexasaccharides found in human milk, pLNH and pLNnH, using a 3+3 convergent coupling strategy.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Nicholas P. Forsythe, Emma R. Mize, Gustavo A. Kashiwagi, Alexei V. Demchenko
Summary: This study reports a streamlined synthetic approach for the production of superarmed glycosyl donors with various leaving groups, and showcases the applicability of this method in the direct formation of disaccharides.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Multidisciplinary
Alessio Romerio, Ana Rita Franco, Melanie Shadrick, Mohammed Monsoor Shaik, Valentina Artusa, Alice Italia, Federico Lami, Alexei V. Demchenko, Francesco Peri
Summary: This study developed a series of structurally simplified synthetic TLR4 agonists as vaccine adjuvants by mimicking the lipid A portion of LPS. Introducing a monosaccharide unit in C6 can improve the target affinity of the new molecules, which showed higher activity and selectivity in vitro.
