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

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

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

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

Identification of crucial residues for the antibacterial activity of the proline-rich peptide, pyrrhocoricin

Members of the proline-rich antibacterial peptide family, pyrrhocoricin, apidaecin and drosocin appear to kill responsive bacterial species by binding to the multihelical lid region of the bacterial DnaK protein. Pyrrhocoricin, the most potent among these peptides, is nontoxic to healthy mice, and can protect these animals from bacterial challenge. A structure-antibacterial activity study of pyrrhocoricin against Escherichia coli and Agrobacterium tumefaciens identified the N-terminal half, residues 2-10, the region responsible for inhibition of the ATPase activity, as the fragment that contains the active segment. While fluorescein-labeled versions of the native peptides entered E. coli cells, deletion of the C-terminal half of pyrrhocoricin significantly reduced the peptide's ability to enter bacterial or mammalian cells. These findings highlighted pyrrhocoricin's suitability for combating intracellular pathogens and raised the possibility that the proline-rich antibacterial peptides can deliver drug leads into mammalian cells. By observing strong relationships between the binding to a synthetic fragment of the target protein and antibacterial activities of pyrrhocoricin analogs modified at strategic positions, we further verified that DnaK was the bacterial target macromolecule. In addition, the antimicrobial activity spectrum of native pyrrhocoricin against 11 bacterial and fungal strains and the binding of labeled pyrrhocoricin to synthetic DnaK D-E helix fragments of the appropriate species could be correlated. Mutational analysis on a synthetic E. coli DnaK fragment identified a possible binding surface for pyrrhocoricin