Indole-3-acetonitrile-4-methoxy-2-C-β-D-glucopyranoside (1), a novel C-glycoside from Isatis indigotica with important cytotoxic activity, has been prepared in ten steps from ethynyl-β-C-glycoside 3 and 2-iodo-3-nitrophenyl acetate 6. Key steps in the synthesis include a Sonogashira coupling and a CuI-mediated indole formation. NMR spectrocopic data for synthetic 1 differs from that reported for the natural product. A revised structure for the natural product, containing an alternate carbohydrate substituent, is proposed.

Golden aryne? Gold aryne complexes are inferred as transition states in dual gold‐catalyzed cyclizations of cis‐enediynes (see scheme; DCE=1,2‐dichloroethane). They are better described as ortho‐aurophenyl cations, which react with weak nucleophiles and undergo facile intramolecular insertions into C(sp3)H bonds. Indanes, fused heteroarenes, and phenol derivatives are readily prepared using this method.

The number of substituted pyridine pyridinophanes found in the literature is limited due to challenges associated with 12-membered macrocycle and modified pyridine synthesis. Most notably, the electrophilic character at the 4-position of pyridine in pyridinophanes presents a unique challenge for introducing electrophilic chemical groups. Likewise, of the few reported, most substituted pyridine pyridinophanes in the literature are limited to electron-donating functionalities. Herein, new synthetic strategies for four new macrocycles bearing the electron-withdrawing groups CN, Cl, NO 2 , and CF 3 are introduced. Potentiometric titrations were used to determine the protonation constants of the new pyridinophanes. Further, the influence of such modifications on the chemical behavior is predicted by comparing the potentiometric results to previously reported systems. X-ray diffraction analysis of the 4-Cl substituted species and its Cu(II) complex are also described to demonstrate the metal binding nature of these ligands. DFT analysis is used to support the experimental findings through energy calculations and ESP maps. These new molecules serve as a foundation to access a range of new pyridinophane small molecules and applications in future work.

Syntheses of the C-glycosyl flavone natural products aspalathin and nothofagin have been accomplished in eight steps from tribenzyl glucal, tribenzyl phloroglucinol, and either 4-benzyloxy phenylacetylene or 3,4-dibenzyloxy phenylacetylene. The key step of the syntheses involves a highly stereoselective Lewis-acid promoted coupling of 1,2-di-O-acyl-3,4,6-tribenzylglucose with tribenzyl phloroglucinol, which gives rise to the corresponding β-C-aryl glycoside in 30-65% yields.Naturally occurring C-aryl glycosides exhibit a range of interesting biological properties. CGlycosyl flavonoids, in particular, have been shown to possess antiviral, cytotoxic, and DNA binding activities. 1 The natural product aspalathin, isolated from the leaves of aspalathus linearis and used in the manufacture of rooibos tea, 2 displays potent antioxidant and radical scavenging activity, 3 and has recently been found to inhibit proliferation and infiltration of liver cancer cells. 4 The structurally related flavonoid nothofagin, typically coisolated with aspalathin, 2 also displays antioxidant properties, but to a lesser extent than aspalathin. Both of these compounds can be considered as direct precursors of a variety of other biologically interesting C-aryl flavonoid natural products, such as orientin/isoorientin, 5 vitexin/isovitexin, 5 and aspalalinin 6 (Figure 1). In view of their impressive biological profile, we decided to undertake total syntheses of both aspalathin and nothofagin.Structurally, both natural products consist of a glucopyranosyl unit carbon-linked to a dihydrochalcone moiety, with β-stereochemistry observed at the anomeric carbon atom. 2 We envisioned that the crucial linkage between the carbohydrate and aromatic subunits could be fashioned by a Lewis-acid promoted Friedel-Crafts-type glycosylation reaction; this process is well-precedented in the literature when highly electron-rich aromatics are employed as nucleophiles, 7,8 and thus this method seemed a logical starting point for our investigations.Addition of TESOTf (1 equiv) to a solution of tribenzylphloroglucinol (2a, 9a 2 equiv) and 2,3,4,6-tetra-O-benzyl glucose-1-O-acetate 9b (1) in CH 2 Cl 2 at 0°C resulted in a clean conversion to the corresponding C-aryl glycoside as a ~3:1 mixture of β:α diastereomers in 89% yield (3a and 3b , Scheme 1). Indeed, Schmidt also previously obtained 3:1 diastereoselectivity in the ZnCl 2 -promoted coupling of 2,3,4,6-tetrabenzyl glucose-1-O-* thomas.minehan@csun.edu . Supporting Information Available Detailed experimental procedures, spectroscopic data, and 1 H and 13 C NMR spectra for compounds in Table 1 and Schemes 1-4. This material is available free of charge on the Internet at http://pubs.acs.org. 10 However, attempted coupling of 2,4,6-trisbenzyloxy acetophenone (2b ,9c 2 equiv) and 1 in the presence of TESOTf (1-5 equivalents) gave only trace quantities (<5%) of the desired C-aryl glycoside product, and unreacted starting materials were recovered in high yield. NIH Public AccessTo circumvent the low diaster...

Abstract:The anti-peroxyl radical quality of two aqueous rooibos infusions and solutions of their most abundant glycosylated polyphenols was evaluated using pyrogallol red and fluorescein-based oxygen radical absorbance ratios. It was observed that the artificial infusions, prepared using only the most abundant polyphenols present in rooibos and at concentrations similar to those found in the natural infusions, showed greater antioxidant OPEN ACCESSMolecules 2013, 18 11265 quality than the latter infusions, reaching values close to those reported for tea infusions. Additionally, the antimicrobial activity of the natural and artificial infusions was assessed against three species of bacteria: Gram (+) Staphylococcus epidermidis and Staphylococcus aureus and Gram (−) Escherichia coli. When compared to the natural infusions the artificial beverages did not demonstrate any bacterostatic/cidal activity, suggesting that the antibacterial activity of rooibos is related to compounds other than the glycosylated polyphenols employed in our study.