In this work, we investigate the potential of highly sulfated synthetic glycomimetics to act as inhibitors of viral binding/infection. Our results indicate that both long-chain glycopolymers and short-chain glycooligomers are capable of preventing viral infection. Notably, glycopolymers efficiently inhibit Human Papillomavirus (HPV16) infection in vitro and maintain their antiviral activity in vivo, while the glycooligomers exert their inhibitory function post attachment of viruses to cells. Moreover, when we tested the potential for broader activity against several other human pathogenic viruses, we observed broad-spectrum antiviral activity of these compounds beyond our initial assumptions. While the compounds tested displayed a range of antiviral efficacies, viruses with rather diverse glycan specificities such as Herpes Simplex Virus (HSV), Influenza A Virus (IAV), and Merkel Cell Polyomavirus (MCPyV) could be targeted. This opens new opportunities to develop broadly active glycomimetic inhibitors of viral entry and infection.

Previously, monodisperse and sequence-controlled oligo(amidoamine) scaffolds were synthesized based on the step-wise assembly of tailor-made building blocks on a solid support that allow for the multivalent presentation of sugar ligands. Here, we extend on this concept using a split-and-combine approach to gain access to a small library of linear and branched glycomacromolecules. Azide side chains were introduced in the scaffold by the use of a novel building block allowing for copper-mediated azide-alkyne cycloaddition (CuAAC) of readily available propargyl-functionalized glycans. In the first stage, after assembly of the linear scaffold on solid support, the batch was divided into two. One part of the resin-bound oligomers was end-capped and further used as backbone and the other part was functionalized with propargylated α-d-mannopyranoside in the sidechain, end capped with an alkyne functionality and finally cleaved from solid support to give the branching arm. In the second stage, the linear, glycosylated and alkynylated arms were then coupled to the end capped backbone via CuAAC. In this way, branched glycomacromolecules with two and three branches, respectively, have been synthesized carrying from two to six sugar residues per molecule. Both, linear arms and branched glycomacromolecules were then subjected to a lectin binding assay using surface plasmon resonance (SPR) and model lectin Concanavalin A (Con A) showing the effect of branching as well as valency on the binding kinetics.

Establishing one-pot, multi-step protocols combining different types of catalysts is one important goal for increasing efficiency in modern organic synthesis.Inparticular, the high potential of biocatalysts still needs to be harvested. Based on an in-depth mechanistic investigation of an ew organocatalytic protocol employing two catalysts {1,4diazabicyclo[2.2.2]octane (DABCO);b enzoic acid (BzOH)}, as equence was established providing starting materials for enzymatic refinement (ene reductase;alcohol dehydrogenase): Ag ram-scale access to av ariety of enantiopure key building blocks for natural product syntheses was enabled utilizing up to six catalytic steps within the same reaction vessel.

Die Etablierung von Eintopf-Mehrschritt-Protokollen, die verschiedene Arten von Katalysatoren kombinieren, ist ein wichtiges Ziel zur Steigerung der Effizienz in der modernen organischen Synthese.I nsbesondere das hohe Potenzial von Biokatalysatoren muss noch ausgeschçpft werden. Basierend auf einer eingehenden mechanistischen Untersuchung eines neuen organokatalytischen Protokolls unter Verwendung zweier Katalysatoren {1,4-Diazabicyclo[2.2.2]octan (DABCO);B enzoesäure (BzOH)} wurde eine Sequenz etabliert, die Ausgangsmaterialien fürd ie enzymatischeV eredelung (Enreduktase;A lkohol-Dehydrogenase) bereitstellt:I ndem bis zu sechs katalytische Schritte innerhalb desselben Reaktionsgefäßes genutzt wurden,konnte ein Zugang zu einer Vielzahl von enantiomerenreinen Schlüsselbausteinen fürd ie Naturstoffsynthese im Grammmaßstab ermçglicht werden.

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