Site-Selective C–O Bond Editing of Unprotected Saccharides

Abstract

Glucose and its polyhydroxy saccharide analogs are complex molecules that serve as essential structural components in biomacromolecules, natural products, medicines, and agrochemicals. Within the expansive realm of saccharides, a significant area of research revolves around chemically transforming naturally abundant saccharide units to intricate or uncommon molecules such as oligosaccharides or rare sugars. However, partly due to the presence of multiple hydroxyl groups with similar reactivities and the structural complexities arising from stereochemistry, the transformation of unprotected sugars to the desired target molecules remains challenging. One such formidable challenge lies in the efficient and selective activation and modification of the C−O bonds in saccharides. In this study, we disclose a modular 2-fold "tagging−editing" strategy that allows for direct and selective editing of C−O bonds of saccharides, enabling rapid preparation of valuable molecules such as rare sugars and drug derivatives. The first step, referred to as "tagging", involves catalytic site-selective installation of a photoredox active carboxylic ester group to a specific hydroxyl unit of an unprotected sugar. The second step, namely, "editing", features a C−O bond cleavage to form a carbon radical intermediate that undergoes further transformations such as C−H and C−C bond formations. Our strategy constitutes the most effective and shortest route in direct transformation and modification of medicines and other molecules bearing unprotected sugars.

Direct Formation of Amide-Linked C-Glycosyl Amino Acids and Peptides via Photoredox/Nickel Dual Catalysis

“…On the basis of the known research ,, and our radical trapping experiments (see Supporting Information), we proposed a plausible mechanism (Figure ). Photoexcitation of the organic photocatalyst 4CzIPN ( E 1/2 (4CzIPN*/4CzIPN •– ) = +1.43 V vs SCE in CH 3 CN) enables the single-electron oxidation of dihydropyridine substrates 2 .…”

Total Synthesis of Nona-decasaccharide Motif from Ganoderma sinense Polysaccharide Enabled by Modular and One-Pot Stereoselective Glycosylation Strategy

“…Chemical synthesis provides a reliable means of solving this accessibility issue. Nonetheless, because of stereoselectivity and regioselectivity issues , during glycans assembly, glycans synthesis remains tedious and time-consuming. While the milestone synthesis of 92-mer arabinogalactan and 101-mer mannose-capped lipoarabinomannan from Mycobacterium tuberculosis , 100-mer and 151-mer mannans, 128-mer O-antigen from Bacteroides vulgatus , 140-mer arabinogalactan from Panax notoginseng , and 1080-mer arabinan has been achieved in recent years, efficient synthesis of long, branched, and complex glycans containing many 1,2- cis -glycosidic linkages over 10-mer remains a challenging task …”

Stereoselective Construction of Multifunctional C-Glycosides Enabled by Nickel-Catalyzed Tandem Borylation/Glycosylation

“…For instance, the Molander group pioneered a dual Ni/photoredox-catalyzed radical cross-coupling of dihydropyridyl sugar motifs to access nonclassical C4- or C5-substituted saccharides . Ngai and Liu disclosed novel metal-catalyzed 1,2-radical migratory reactions to build C2-functionalized 2-deoxy sugars. , Very recently, the Chi group exploited an elegant “tagging-editing” strategy that converts photoredox-active glycosyl esters into C3- or C6-functionalized deoxygenated sugars …”