A Multiplexing Activity-Based Protein-Profiling Platform for Dissection of a Native Bacterial Xyloglucan-Degrading System.

Bacteria and yeasts grow on biomass polysaccharides by expressing and excreting a complex array of glycoside hydrolase (GH) enzymes. Identification and annotation of such GH pools, which are valuable commodities for sustainable energy and chemistries, by conventional means (genomics, proteomics) are complicated, as primary sequence or secondary structure alignment with known active enzymes is not always predictive for new ones. Here we report a "low-tech", easy-to-use, and sensitive multiplexing activity-based protein-profiling platform to characterize the xyloglucan-degrading GH system excreted by the soil saprophyte, , when grown on xyloglucan.

Synthesis of biolabile thioalkyl-protected phosphates from an easily accessible phosphotriester precursor.

Robust methods for the synthesis of mixed phosphotriesters are essential to accelerate the development of novel phosphate-containing bioactive molecules. To enable efficient cellular uptake, phosphate groups are commonly masked with biolabile protecting groups, such as -acyl-2-thioethyl (SATE) esters, that are removed once the molecule is inside the cell. Typically, bis-SATE-protected phosphates are synthesised through phosphoramidite chemistry.

Synthesis, conformational analysis and glycosidase inhibition of bicyclic nojirimycin C-glycosides based on an octahydrofuro[3,2-b]pyridine motif.

A set of bicyclic iminosugar C-glycosides, based on an octahydrofuro[3,2-b]pyridine motif, has been synthesized from a C-allyl iminosugar exploiting a debenzylative iodocycloetherification and an iodine nucleophilic displacement as the key steps. The halogen allowed the introduction of a range of aglycon moieties of different sizes bearing several functionalities such as alcohol, amine, amide and triazole. In these carbohydrate mimics the fused THF ring forces the piperidine to adopt a flattened C conformation according to NMR and DFT calculations studies.

Synthesis and glycosidase inhibition of conformationally locked DNJ and DMJ derivatives exploiting a 2-oxo-C-allyl iminosugar.

A series of analogs of the iminosugars 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (DMJ), in which an extra five or six-membered ring has been fused to the C1-C2 bond have been prepared. The synthetic strategy exploits a key 2-keto-C-allyl iminosugar, easily accessible from gluconolactam, which upon Grignard addition and RCM furnishes a bicyclic scaffold that can be further hydroxylated at the C[double bond, length as m-dash]C bond. This strategy furnished DNJ mimics with the piperidine ring locked in a C conformation with all substituents in axial orientation when fused to a six-membered ring.

Site-Selective Debenzylation of C-Allyl Iminosugars Enables Their Stereocontroled Structure Diversification at the C-2 Position.

A C-2 regioselective debenzylative cycloetherification/reductive elimination sequence applied to perbenzylated C-allyl iminosugars is described. This NIS/TMSOTf-triggered deprotection was successfully applied to five-, six-, and seven-membered C-allyl iminosugars including 1,2 cis and 1,2 trans stereoisomers. It allows rapid introduction of structural diversity at the key C-2 position in a stereoselective manner exploiting the anchimeric assistance of the intracyclic N-benzyl group, giving access to the 2-acetamido and 2-fluoro d-gluco configured C-allyl iminosugars and to the epimeric d-manno derivative.