Design and Synthesis of Exocyclic Cyclitol Aziridines as Potential Mechanism-Based Glycosidase Inactivators

Cyclophellitol aziridines have found wide application as mechanism-based, covalent, and irreversible inhibitors of retaining glycosidases. These compounds, like their parent compound, cyclophellitol (a natural product retaining β-glucosidase inactivator), make use of the mechanism of action of retaining glycosidases, which process their substrate through the formation of a transient covalent intermediate. In contrast, inverting glycosidases, the other main family of glycosyl hydrolases, do not employ such a covalent intermediate, and, as a consequence, useful scaffolds for mechanism-based inhibitor design have yet to be discovered. In this work, we explore chemistries that allow for the construction of cyclitol aziridines with the aziridine electrophile attached in an exocyclic fashion, more distal from the anomeric carbon – thus putatively closer to an inverting glycosidase active site nucleophile. The developed chemistries have allowed for the synthesis of a focused library of differently N-substituted, α-and β-glucopyranose configured cyclitol aziridines for future evaluation as inhibitors or inactivators of α-and β-glucosidases alike.     

Selective Oxidative Dehydrogenation of Ethane and Propane over Copper-Containing Mordenite: Insights into Reaction Mechanism and Product Protection

Copper(II)-containing mordenite (CuMOR) is capable of activation of C−H bonds in C₁-C₃ alkanes, albeit there are remarkable differences between the functionalization of ethane and propane compared to methane. The reaction of ethane and propane with CuMOR results in the formation of ethylene and propylene, while the reaction of methane predominantly yields methanol and dimethyl ether. By combining in situ FTIR and MAS NMR spectroscopies as well as time-resolved Cu K-edge X-ray absorption spectroscopy, the reaction mechanism was derived, which differs significantly for each alkane. The formation of ethylene and propylene proceeds via oxidative dehydrogenation of the corresponding alkanes with selectivity above 95 % for ethane and above 85 % for propane. The formation of stable π-complexes of olefins with Cu^I sites, formed upon reduction of Cu^II-oxo species, protects olefins from further oxidation and/or oligomerization. This is different from methane, the activation of which proceeds via oxidative hydroxylation leading to the formation of surface methoxy species bonded to the zeolite framework. Our findings constitute one of the major steps in the direct conversion of alkanes to important commodities and open a novel research direction aiming at the selective synthesis of olefins.     

Mechanistic Characterisation and Engineering of Sesterviolene Synthase from Streptomyces violens

The sesterviolene synthase from Streptomyces violens was identified and represents the second known sesterterpene synthase from bacteria. Isotopic labelling experiments in conjunction with DFT calculations were performed that provided detailed insight into its complex cyclisation mechanism. Enzyme engineering through site-directed mutagenesis gave access to a high-yielding enzyme variant that provided six additional minor products and the main product in sufficient quantities to study its chemistry.     

Gas separation membranes from tailor-made polymers

The development of tailor-made polymers as new gas separation membrane materials has lead to membranes allowing both higher selectivities as well as higher permeabilities. The increased productivity of these new membrane materials is explained in terms of a higher free volume available for gas transport.