Stereocontrol and other mechanistic aspects of chemical glycosylation.
Development of new reagents, protecting groups, and building blocks
The application of partially protected building blocks is fundamental to carbohydrate chemistry. Poor accessibility to building blocks hampers the development of all synthetic methods and researchers experience significant setbacks because they must continue to remake building blocks. There are no universal building blocks, protecting groups, reagents, or methods for the synthesis of glycans. My lab has been working on developing new protecting groups and advanced synthetic intermediates that will provide streamlined access to regioselectively protected building blocks. Many of these projects involve undergraduate trainees who become co-authors on articles and presentations. In recent years, we have also initiated a program dedicated to the development of new catalysts and protocols for catalytic activation and modification of carbohydrates.
Escopy, Y. Singh, K. J. Stine, and A. V. Demchenko. A Streamlined regenerative glycosylation reaction: direct, acid-free activation of thioglycosides. Chem. Eur. J., 2021, 27, 354-361 (Hot Paper)
PMID: 32804435 (2R01-12, U01-26)
A. Geringer, M. P. Mannino, M. D. Bandara, and A. V. Demchenko. Picoloyl protecting group in synthesis: focus on a highly chemoselective catalytic removal. Org. Biomol. Chem., 2020, 18, 4863-4871
PMID: 32608450 (3NSF-15, 2R01-7)
C. Alex, S. Visansirikul, Y. Zhang, J. P. Yasomanee, J. Codee, and A. V. Demchenko. Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno derivatives as versatile building blocks. Carbohydr. Res., 2020, 488, 107900;
PMID: 31901454 (3NSF-10, U01-21)
Stereocontrolled glycosylation: reactions and mechanism
Many complex sugars have an oligomeric sequence wherein monosaccharides are linked via O-glycosidic linkages. This linkage is obtained by a glycosylation reaction which, despite significant progress, remains challenging due to the requirement to achieve complete stereocontrol and to suppress side reactions. To address these challenges, my lab introduced the thioimidate glycosylation approach, discovered the O-2/O-5 cooperative effect in glycosylation, and invented an ether-type participating group. My team developed many methods for 1,2-cis glycosylation including bromine-activated glycosidation of thioglycosides, H-bond mediated aglycone delivery, and a metal-coordination approach to controlling stereoselectivity. More recently, my lab invented a concept of the regenerative glycosylation reaction, developed glycosyl donors with switchable stereoselectivity, and showed how traditional Koenigs-Knorr glycosylations can be enhanced by cooperative acid catalysis.
H. B. Steber, Y. Singh, and A. V. Demchenko. Bismuth(III) triflate as a novel and efficient activator for glycosyl halides. Org. Biomol. Chem., 2021, 19, 3220-3233
PMID: 33885577 (2R01-15, 3NSF-23)
C. Alex, S. Visansirikul, and A. V. Demchenko. A versatile approach to the synthesis of glycans containing mannuronic acid residues. Org. Biomol. Chem., 2021, 19, 2731-2743
PMID: 33687051 (3NSF-22)
S. Escopy, Y. Singh, and A. V. Demchenko. Palladium(II)-assisted activation of thioglycosides. Org. Biomol. Chem., 2021, 19, 2044-2054
PMID: 33599667 (2R01-14, 3NSF-21)
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