Real-time monitoring of solid-phase peptide synthesis using a variable bed flow reactor

On-resin aggregation and incomplete amide bond formation are major challenges for solid-phase peptide synthesis that are difficult to be monitored in real-time. Incorporation of a pressure-based variable bed flow reactor into an automated solid-phase peptide synthesizer permitted real-time monitoring of resin swelling to determine amino acid coupling efficiency and on-resin aggregation

Parametric Analysis of Donor Activation for Glycosylation Reactions

The chemical synthesis of complex oligosaccharides relies on efficient and highly reproducible glycosylation reactions. The outcome of a glycosylation is contingent upon several environmental factors, such as temperature, acidity, the presence of residual moisture, as well as the steric, electronic, and conformational aspects of the reactants. Each glycosylation proceeds rapidly and with a high yield within a rather narrow temperature range. For better control over glycosylations and to ensure fast and reliable reactions, a systematic analysis of 18 glycosyl donors revealed the effect of reagent concentration, water content, protecting groups, and structure of the glycosyl donors on the activation temperature. With these insights, we parametrize the first step of the glycosylation reaction to be executed reliably and efficiently

Enabling Technologies in Carbohydrate Chemistry: Automated Glycan Assembly, Flow Chemistry and Data Science

The synthesis of defined oligosaccharides is a complex task. Several enabling technologies have been introduced in the last two decades to facilitate synthetic access to these valuable biomolecules. In this concept, we describe the technological solutions that have advanced glycochemistry using automated glycan assembly, flow chemistry and data science as examples. We highlight how the synergies between these different technologies can further advance the field, with progress toward the realization of a self‐driving lab for glycan synthesis

Phosphates as Assisting Groups in Glycan Synthesis

In nature, phosphates are added to and cleaved from molecules to direct biological pathways. The concept was adapted to overcome limitations in the chemical synthesis of complex oligosaccharides. Phosphates were chemically placed on synthetic glycans to ensure site-specific enzymatic elongation by sialylation. In addition, the deliberate placement of phosphates helped to solubilize and isolate aggregating glycans. Upon traceless removal of the phosphates by enzymatic treatment with alkaline phosphatase, the native glycan structure was revealed, and the assembly of glycan nanostructures was triggered

VaporSPOT: Parallel Synthesis of Oligosaccharides on Membranes

Automated chemical synthesis has revolutionized synthetic access to biopolymers in terms of simplicity and speed. While automated oligosaccharide synthesis has become faster and more versatile, the parallel synthesis of oligosaccharides is not yet possible. Here, a chemical vapor glycosylation strategy (VaporSPOT) is described that enables the simultaneous synthesis of oligosaccharides on a cellulose membrane solid support. Different linkers allow for flexible and straightforward cleavage, purification, and characterization of the target oligosaccharides. This method is the basis for the development of parallel automated glycan synthesis platforms

Drying colloidal systems: laboratory models for a wide range of applications

The drying of complex fluids provides a powerful insight into phenomena that take place on time and length scales not normally accessible. An important feature of complex fluids, colloidal dispersions and polymer solutions is their high sensitivity to weak external actions. Thus, the drying of complex fluids involves a large number of physical and chemical processes. The scope of this review is the capacity to tune such systems to reproduce and explore specific properties in a physics laboratory. A wide variety of systems are presented, ranging from functional coatings, food science, cosmetology, medical diagnostics and forensics to geophysics and art

On resin synthesis of sulfated oligosaccharides

Sulfated glycans are involved in many biological processes, making well-defined sulfated oligosaccharides highly sought molecular probes. These compounds are a considerable synthetic challenge, with each oligosaccharide target requiring specific synthetic protocols and extensive purifications steps. Here, we describe a general on resin approach that simplifies the synthesis of sulfated glycans. The oligosaccharide backbone, obtained by Automated Glycan Assembly (AGA), is subjected to regioselective sulfation and hydrolysis of protecting groups. The protocol is compatible with several monosaccharides and allows for multi-sulfation of linear and branched glycans. Seven diverse, biologically relevant sulfated glycans were prepared in good to excellent overall yield

Visible-Light-Mediated Oxidative Debenzylation Enables the Use of Benzyl Ethers as Temporary Protecting Groups

The cleavage of benzyl ethers by catalytic hydrogenolysis or Birch reduction suffers from poor functional group compatibility and limits their use as a protecting group. The visible-light-mediated debenzylation disclosed here renders benzyl ethers temporary protective groups, enabling new orthogonal protection strategies. Using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a stoichiometric or catalytic photooxidant, benzyl ethers can be cleaved in the presence of azides, alkenes, and alkynes. The reaction time can be reduced from hours to minutes in continuous flow