The first "In Water" imidazolecarbonylation of amine is described. A one pot reaction of carbonylimidazolide in water with a nucleophile provides an efficient and general method for the preparation of urea, carbamates and thiocarbamates. Use of an anhydrous solvent and an inert atmosphere could be avoided. Product precipitate out from the reaction mixture and can be obtained in high purity by filtration, resulting in a simple and scalable method.
The first total synthesis of isofregenedadiol, a bicyclic diterpene isolated from H. Viscosum, is reported starting from a D-(-)-pantolactone chiral pool. A one-pot quadruple reaction sequence comprising an enyne ring-closing metathesis/cross-metathesis/Diels-Alder/aromatization for the construction of a target skeleton is the highlight of the present synthesis.
An engineered cyanovirin‐N homologue that exhibits specificity for high mannose N‐glycans has been constructed to aid type I α 1,2‐mannosidase inhibitor discovery and development. Engineering the lectins C‐terminus permitted facile functionalization with fluorophores via a sortase and click strategy. The resulting lectin constructs exhibit specificity for cells presenting high mannose N‐glycans. Importantly, these lectin constructs can also be applied to specifically assess changes in cell surface glycosylation induced by type I mannosidase inhibitors. Testing the utility of these lectin constructs led to the discovery of type I mannosidase inhibitors with nanomolar potency. Cumulatively, these findings reveal the specificity and utility of the functionalized cyanovirin‐N homologue constructs, and highlight their potential in analytical contexts that require high mannose‐specific lectins.
An efficient and convenient method for the synthesis of sugar-lactam conjugates is reported starting from readily available sugar azides using the Aubé reaction. Cyclic azido alcohols are used in the Aubé reaction for the first time in a carbohydrate setting. The resulting glycoconjugates could be further used to increase the chemical diversity on the sugar backbone, and may find potential applications as glycomimetics, peptidomimetics, in glycotargeting and in CNS drug delivery.
Cancer-associated alterations to glycosylation have been shown to aid cancer development and progression. An increased abundance of high mannose N-glycans has been observed in several cancers. Here, we describe the preparation of lectin drug conjugates (LDCs) that permit toxin delivery to cancer cells presenting high mannose N-glycans. Additionally, we demon-strate that cancer cells presenting low levels of high mannose N-glycans can be rendered sensitive to the LDCs by cotreatment with a type I mannosidase inhibitor. Our findings establish that an increased abundance of high mannose Nglycans in the glycocalyx of cancer cells can be leveraged to enable toxin delivery.
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