Solvent and Temperature Effects in π-Route Cyclization

endo-Bicyclo[3.3.1]non-6-ene-3-carboxylic acid (1) was prepared and the solvent and temperature effects on the n-route cyclization were studied. The stereochemistry of the products strongly depends on the reaction temperature and the solvent used. The interpretation of the mechanism and product distribution based on experimental data is supported by theoretical investigation

Photochemistry of p-(5-Substituted-2-furyl)-o-divinylbenzenes; Substituent Effects on the Reaction Course

Irradiation of 2-[2-(2-vinylphenyl)ethenyl]furan (la) and 5-methyl- 2-[2-(2-vinylphenyl)ethenyl]furan (lb) gave 9,10-đihydro-4,9-me- thano-4ff-benzo[4,5]cyclohepta[l,2-6]furan (2a) and 9,10-dihydro- 2-methyl-4,9-methano-4H-benzo[4,5]cyclohepta[l,2-b]furan (2b), respectively, in a very good yield in addition to traces of 5. Contrary to these results, the 5-substituted furan derivatives 1 (c: R = CN; d: R = P-C6H4CH3, e: R = OCH3) gave mainly, upon irradiation under the same conditions, isomerization about the double bond, high-molecular-weight products, small amount of phenanthrenes 5 and only traces of bicyclic structure 2

Uptake of the antifungal cationic peptide Histatin 5 by Candida albicans Ssa2p requires binding to non-conventional sites within the ATPase domain

Candida albicans Hsp70 Ssa1/2 proteins have been identified as cell wall binding partners for the antifungal cationic peptide Histatin 5 (Hst 5) in vivo. C. albicans Ssa2p plays a major role in binding and translocation of Hst 5 into fungal cells, as demonstrated by defective peptide uptake and killing in C. albicans SSA2 null mutants. Candidal Hsp70 proteins are classical chaperone proteins with two discrete functional domains consisting of peptide binding and ATP binding regions. Pull-down assays with full-length and truncated Ssa2 proteins found that the ATPase domain was required for Hst 5 binding. Further mapping of Ssa2p by limited digestion and peptide array analyses identified two discrete Hst 5-binding epitopes within the ATPase region. Expression of Ssa2p in C. albicans cells carrying mutations in the first epitope identified by thermolysin digestion (Ssa2128−132A3) significantly reduced intracellular transport and fungicidal activity of Hst 5, confirming its importance as a binding site for Hst 5 function in vivo. Since this Hst 5 binding site lies within the Ssa2p ATPase domain near the ATP-binding cleft, it is possible that ATP modulates Hst 5 binding to Ssa2p. Indeed, gel filtration assays demonstrated that although nucleotides are not required for Hst 5 binding, their presence improved binding affinity by 10-fold. Thus, C. albicans Ssa2p binds Hst 5 at a surface-localized epitope in a subunit of the ATPase domain; and this region is required for intracellular translocation and killing functions of Hst 5

The Potential of Antimicrobial Peptides as Biocides

Antimicrobial peptides constitute a diverse class of naturally occurring antimicrobial molecules which have activity against a wide range of pathogenic microorganisms. Antimicrobial peptides are exciting leads in the development of novel biocidal agents at a time when classical antibiotics are under intense pressure from emerging resistance, and the global industry in antibiotic research and development stagnates. This review will examine the potential of antimicrobial peptides, both natural and synthetic, as novel biocidal agents in the battle against multi-drug resistant pathogen infections

Unprecedented Epimerization of an Azithromycin Analogue: Synthesis, Structure and Biological Activity of 2′-Dehydroxy-5″-Epi-Azithromycin

Certain macrolide antibiotics, azithromycin included, possess anti-inflammatory properties that are considered fundamental for their efficacy in the treatment of chronic inflammatory diseases, such as diffuse pan-bronchiolitis and cystic fibrosis. In this study, we disclose a novel azithromycin analog obtained via Barton–McCombie oxidation during which an unprecedented epimerization on the cladinose sugar occurs. Its structure was thoroughly investigated using NMR spectroscopy and compared to the natural epimer, revealing how the change in configuration of one single stereocenter (out of 16) profoundly diminished the antimicrobial activity through spatial manipulation of ribosome binding epitopes. At the same time, the anti-inflammatory properties of parent macrolide were retained, as demonstrated by inhibition of LPS- and cigarette-smoke-induced pulmonary inflammation. Not surprisingly, the compound has promising developable properties including good oral bioavailability and a half-life that supports once-daily dosing. This novel anti-inflammatory candidate has significant potential to fill the gap in existing anti-inflammatory agents and broaden treatment possibilities