Cyclophellitol and cyclophellitol aziridine are potent and irreversible inhibitors of retaining β‐glucosidases. They preferentially adopt a 4H3 half‐chair conformation, thereby mimicking the... Show moreCyclophellitol and cyclophellitol aziridine are potent and irreversible inhibitors of retaining β‐glucosidases. They preferentially adopt a 4H3 half‐chair conformation, thereby mimicking the substrate‐transition‐state conformation characteristic of retaining β‐glucosidases. As a consequence, both compounds bind tightly to the enzyme active site, and attack of the catalytic nucleophile onto the epoxide/aziridine results in enzyme deactivation. Replacement of the epoxide oxygen in cyclophellitol by a (substituted) carbon yielded carba‐cyclophellitols, a conceptually new class of inhibitors of retaining β‐glucosidases, as we demonstrated in a recent communication. In this paper, in‐depth synthetic studies of this class of compounds are described, and the preparation of a comprehensive set of structurally and configurationally new carba‐cyclophellitols is presented. Show less
Carbohydrates or sugars, the most diverse class of biopolymers, are involved in many different biological processes. To be able to study these processes, well defined sugar structures are required.... Show moreCarbohydrates or sugars, the most diverse class of biopolymers, are involved in many different biological processes. To be able to study these processes, well defined sugar structures are required. The synthesis of these sugar structures is at this moment far from ideal and therefore requires fundamental research, in particular towards the glycosylation reaction. In this reaction a positively charged oxocarbenium ion can be considered as the product forming intermediate, the cation is however commonly reasoned to lead to non-selective reactions and product mixtures. Chemical calculations on the oxocarbenium ion combined with model glycosylations proved the contrary, namely that these oxocarbenium ions are in fact selective. With these results, insight into the glycosylation mechanism is improved. The orientation of specific substituents on the sugar ring proved to have a profound influence on the stability of the oxocarbenium ion and thereby on the stereochemical outcome of glycosylations. Show less
