Diverse Applications of Biomass-Derived 5-Hydroxymethylfurfural and Derivatives as Renewable Starting Materials.

This Review summarizes recent efforts to capitalize on 5-hydroxymethylfurfural (HMF) and related furans as emerging building blocks for the synthesis of fine chemicals and materials, with a focus on advanced applications within medicinal and polymer chemistry, as well as nanomaterials. As with all chemical industries, these fields have historically relied heavily on petroleum-derived starting materials, an unsustainable and polluting feedstock. Encouragingly, the emergent chemical versatility of biomass-derived furans has been shown to facilitate derivatization towards valuable targets. Continued work on the synthetic manipulation of HMF, and related derivatives, for access to a wide range of target compounds and materials is crucial for further development. Increasingly, biomass-derived furans are being utilized for a wide range of chemical applications, the continuation of which is paramount to accelerate the paradigm shift towards a sustainable chemical industry.

Synthesis of 2,5-Diaryl Nonsymmetric Furans C6-Platform Chemicals via Catalytic Conversion of Biomass and the Formal Synthesis of Dantrolene.

Biomass-derived commodity chemical 5-hydroxymethyl furfural is an underutilized C6-platform chemical derived from cellulose that is ideal to prepare next-generation value-added products. We have developed an efficient synthetic strategy to access 2,5-diaryl nonsymmetric furans from 5-hydroxymethyl furfural utilizing decarboxylative cross-couplings. A key finding was that the presence of the hydroxymethyl handle enhances the yields of the palladium-catalyzed decarboxylative cross-coupling reaction. The method provides access to a broad-range nonsymmetric 2,5-diaryl furans where each arene can be systematically introduced as required. Additionally, this green synthetic strategy was employed for a formal synthesis of the muscle relaxant Dantrolene in excellent yields.

A High-Throughput Glycosyltransferase Inhibition Assay for Identifying Molecules Targeting Fucosylation in Cancer Cell-Surface Modification.

In cancers, increased fucosylation (attachment of fucose sugar residues) on cell-surface glycans, resulting from the abnormal upregulation of the expression of specific fucosyltransferase enzymes (FUTs), is one of the most important types of glycan modifications associated with malignancy. Fucosylated glycans on cell surfaces are involved in a multitude of cellular interactions and signal regulation in normal biological processes, as well as in disease. For example, sialyl LewisX is a fucosylated cell-surface glycan that is abnormally abundant in some cancers where it has been implicated in facilitating metastasis, allowing circulating tumor cells to bind to the epithelial tissue within blood vessels and invade into secondary sites by taking advantage of glycan-mediated interactions. To identify inhibitors of FUT enzymes as potential cancer therapeutics, we have developed a novel high-throughput assay that makes use of a fluorogenically labeled oligosaccharide as a probe of fucosylation. This probe, which consists of a 4-methylumbelliferyl glycoside, is recognized and hydrolyzed by specific glycoside hydrolase enzymes to release fluorescent 4-methylumbelliferone, yet when the probe is fucosylated prior to treatment with the glycoside hydrolases, hydrolysis does not occur and no fluorescent signal is produced. We have demonstrated that this assay can be used to measure the inhibition of FUT enzymes by small molecules, because blocking fucosylation will allow glycosidase-catalyzed hydrolysis of the labeled oligosaccharide to produce a fluorescent signal. Employing this assay, we have screened a focused library of small molecules for inhibitors of a human FUT enzyme involved in the synthesis of sialyl LewisX and demonstrated that our approach can be used to identify potent FUT inhibitors from compound libraries in microtiter plate format.