We herein described the design, synthesis and application of two recyclable benzyl-type fluorous tags with double fluorous chains. The benzyl-type fluorous tags were prepared in 3 steps from a commercially available fluorous alcohol. The glycosylation of the benzyl-type tags with imidate donors proceeded smoothly to provide the corresponding fluorous-tagged carbohydrates in good to excellent yields, which were readily purified by fluorous solid-phase extraction (FSPE). Efficient removal of the tags from tag-tethered carbohydrates were conducted under the common catalytic hydrogenation condition and the initial benzyl-type fluorous tags could be regenerated via a 2-step simple procedure in 69%–93% yields. The utility of the new benzyl-fluorous tag was demonstrated via the FSPE-assisted synthesis of oligosaccharides Gb3.Download high-res image (130KB)Download full-size imageTwo recyclable benzyl-type fluorous tags with double fluorous chains were designed, synthesized and applied to the synthesis of oligosaccharide Gb3.

G-quadruplex formation at the end of telomeres is one of the effective pathways for inhibiting the growth of cancer cells induced by up-regulation of telomerase. The lack of effective G-quadruplex-binding ligands has strongly limited the discovery of telomerase-targeted cancer drugs. To address these limitations, the development of a high-throughput screening technique is urgent and meaningful for the discovery of potent telomerase inhibitors from the large chemical libraries of candidates. Here, we present a fast and cost-effective method to realize high-throughout screening of G-quadruplex-binding ligands based on G-quadruplex formation induced fluorescence quenching. Carboxyfluorescein-labeled hairpin DNA (F-hpDNA) was designed as a molecular recognition probe. In the presence of G-quadruplex ligands, the conformation of the F-hpDNA switched from hairpin into G-quadruplex, leading to a significant decrease in the fluorescence of F-hpDNA due to photo-induced electron transfer (PIET) between fluorophore and G-quartet. So, ligands were selected by using the G-quadruplex as a natural fluorescence quencher, which means the DNA probe is just single-labeled. A variety of ligands can be simultaneously screened within several minutes. To verify the formation of G-quadruplex, circular dichroism (CD) analysis has been performed to study ligand-induced conformation change. Moreover, the fluorescence microscopy image and MTT cell proliferation assay all demonstrated that the selected ligand has the potential to inhibit the growth of cancer cells. For the first time, a high-throughout method based on PIET was established to quickly, cost-effectively and reliably identify G-quadruplex ligands, which is of great theoretical and practical importance for the discovery of telomerase-targeted anticancer drugs.

We have developed an easy and practical method for the synthesis of α,β-unsaturated oximes and nitriles from readily available propargylic alcohols with hydroxylamine hydrochloride (NH2OH·HCl) under metal-free conditions. By using or not using p-toluenesulfonyl chloride (p-TsCl) as the dehydrating promoter, the desired nitriles or oximes could be obtained, respectively via a three-step one-pot or two-step one-pot process in moderate to excellent yields with good functional group compatibility.