To probe the reaction mechanism, underlying the rearrangementofoft-used trichloroacetimidate glycosyl donors into the correspondinganomeric trichloroacetamides, we have used a combination of C-13-... Show moreTo probe the reaction mechanism, underlying the rearrangementofoft-used trichloroacetimidate glycosyl donors into the correspondinganomeric trichloroacetamides, we have used a combination of C-13- and N-15-labeled glycosyl trichloroacetimidate donorsin a series of crossover experiments. These unambiguously show thattrichloroacetamides are formed via an intermolecular aglycon transfermechanism. This insight enables the design of more effective glycosylationprotocols, preventing the formation of dead-end side products. Show less
Madern, J.M.; Voorneveld, J.; Rack, J.G.M.; Kistemaker, H.A.V.; Ahel, I.; Marel, G.A. van der; ... ; Filippov, D.V. 2023
Adenosine diphosphate (ADP) ribosylation is an importantpost-translationalmodification (PTM) that plays a role in a wide variety of cellularprocesses. To study the enzymes responsible for the... Show moreAdenosine diphosphate (ADP) ribosylation is an importantpost-translationalmodification (PTM) that plays a role in a wide variety of cellularprocesses. To study the enzymes responsible for the establishment,recognition, and removal of this PTM, stable analogues are invaluabletools. We describe the design and synthesis of a 4-thioribosyl APRrpeptide that has been assembled by solid phase synthesis. The key4-thioribosyl serine building block was obtained in a stereoselectiveglycosylation reaction using an alkynylbenzoate 4-thioribosyl donor. Show less
Herein, we describe a novel methodology for the regio-and stereoselectiveconvergent synthesis of 2-amino-2-deoxy-dithioglycosides via one-potrelay glycosylation of 3-O-acetyl-2-nitroglucal donors... Show moreHerein, we describe a novel methodology for the regio-and stereoselectiveconvergent synthesis of 2-amino-2-deoxy-dithioglycosides via one-potrelay glycosylation of 3-O-acetyl-2-nitroglucal donors.This unique organo-catalysis relay glycosylation features excellentsite- and stereoselectivity, good to excellent yields, mild reactionconditions, and broad substrate scope. 2-Amino-2-deoxy-glucosides/mannosidesbearing 1,3-dithio-linkages were efficiently obtained from 3-O-acetyl-2-nitroglucal donors in both stepwise and one-potglycosylation protocols. The dithiolated O-antigen of E. coli serogroup 64 was successfully synthesizedusing this newly developed method. Show less
Minnee, H.; Rack, J.G.M.; Marel, G.A. van der; Overkleeft, H.S.; Codee, J.D.C.; Ahel, I.; Filippov, D.V. 2022
A convergent synthesis provided nearly perfect tau-ADP-ribosylated histidine isosteres (His*-tau-ADPr) via a copper(I)-catalyzed cycloaddition between an azido-ADP-ribosyl analogue and an... Show moreA convergent synthesis provided nearly perfect tau-ADP-ribosylated histidine isosteres (His*-tau-ADPr) via a copper(I)-catalyzed cycloaddition between an azido-ADP-ribosyl analogue and an oligopeptide carrying a propargyl glycine. Both alpha- and beta-configured azido-ADP-ribosyl analogues have been synthesized. The former required participation of the C-2 ester functionality during glycosylation, while the latter was obtained in high stereoselectivity from an imidate donor with a nonparticipating para-methoxy benzyl ether. Four His*-tau-ADPr peptides were screened against a library of human ADP-ribosyl hydrolases. Show less
Ofman, T.P.; Küllmer, F.; Marel, G.A. van der; Codée, J.D.C.; Overkleeft, H.S. 2021
Cyclophellitols are potent inhibitors of exo- and endoglycosidases. Efficient synthetic methodologies are needed to fully capitalize on this intriguing class of mechanism-based enzyme deactivators.... Show moreCyclophellitols are potent inhibitors of exo- and endoglycosidases. Efficient synthetic methodologies are needed to fully capitalize on this intriguing class of mechanism-based enzyme deactivators. We report the synthesis of an orthogonally protected cyclitol from d-glucal (19% yield over 12 steps) and its use in the synthesis of α-(1,3)-linked di- and trisaccharide dextran mimetics. These new glycomimetics may find use as Dextranase inhibitors, and the developed chemistries in widening the palette of glycoprocessing enzyme-targeting glycomimetics. Show less
The 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) group permits, via robust neighboring group participation (NGP) or long distance participation (LDP) effects, the stereocontrolled 1,2-trans, 1,2-.Show moreThe 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) group permits, via robust neighboring group participation (NGP) or long distance participation (LDP) effects, the stereocontrolled 1,2-trans, 1,2-cis, as well as β-2,6-dideoxy glycosidic bond generation, while suppressing the undesired orthoester byproduct formation. The robust stereocontrol capability of the DMNPA is due to the dual-participation effect from both the ester functionality and the nitro group, verified by control reactions and DFT calculations and further corroborated by X-ray spectroscopy. Show less
Voorneveld, J.; Rack, J.G.M.; Ahel, I.; Overkleeft, H.S.; Marel, G.A. van der; Filippov, D.V. 2018
