A Formal Total Synthesis of (+)-Methyl Trachyloban-18-oate and (+)-Methyl 16-Oxo-17-norkauran-18-oate: Regio- and Diastereoselective Preparation of Methyl (13S)-13-Hydroxyisoatisiren-18-oate from (−)-Abietic Acid

A novel preparation of methyl (13S)-13-hydroxyisoatisiren-18-oate ( 4 ), a key-intermediate in a synthesis of (+)-methyl trachyloban-18-oate ((+)- 1 ), from (?)-abietic acid, is described. Since (?)- 1 has been previously converted into (?)-methyl 16-oxo-17-norkauran-18-oate ((?)- 16 ), our preparation of 4 constitutes also a formal total synthesis, from (?)-abietic acid, of (+)- 16 . Key steps in this approach were the allene photoaddition to podocarp-8(14)-en-13-one ( 5 ) and the conversion of the endo-toluene-4-sulfonate 11 into the exo-benzoate 12b .     

Water-soluble gold nanoparticles protected by fluorinated amphiphilic thiolates

The preparation and the properties of gold nanoparticles (Au NPs) protected by perfluorinated amphiphiles are described. The thiols were devised to form a perfluorinated region close to the gold surface and to have a hydrophilic portion in contact with the bulk solvent to impart solubility in water. The monolayer protected clusters were prepared, in an homogeneous phase using sodium thiolates because of the low nucleophilicity of the alpha-perfluorinated thiols, and fully characterized with (1)H, (19)F NMR spectrometry, IR and UV-vis absorption spectroscopies, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). Au NPs with core diameters ranging from 1.6 to 2.9 nm, depending on the reaction conditions, were obtained. Water-soluble NPs (MPC-F8-PEGs) were obtained with the thiol HS-F8-PEG ending with a short poly(ethylene glycol) unit (PEG-OMe 550), whereas thiols with shorter PEG chains give rise to NPs insoluble in water. MPC-F8-PEGs undergo an exchange reaction with amphiphilic alkyl thiols. ESR investigations, using a hydrophobic radical probe, indicate that the MPC-F8-PEG monolayer shows a greater hydrophobicity compared to the analogous hydrogenated monolayer.     

Marine derived polysaccharides for biomedical applications: chemical modification approaches

Polysaccharide-based biomaterials are an emerging class in several biomedical fields such as tissue regeneration, particularly for cartilage, drug delivery devices and gelentrapment systems for the immobilization of cells. Important properties of the polysaccharides include controllable biological activity, biodegradability, and their ability to form hydrogels. Most of the polysaccharides used derive from natural sources; particularly, alginate and chitin, two polysaccharides which have an extensive history of use in medicine, pharmacy and basic sciences, and can be easily extracted from marine plants (algae kelp) and crab shells, respectively. The recent rediscovery of poly-saccharidebased materials is also attributable to new synthetic routes for their chemical modification, with the aim of promoting new biological activities and/or to modify the final properties of the biomaterials for specific purposes. These synthetic strategies also involve the combination of polysaccharides with other polymers. A review of the more recent research in the field of chemical modification of alginate, chitin and its derivative chitosan is presented. Moreover, we report as case studies the results of our recent work concerning various different approaches and applications of polysaccharide-based biomaterials, such as the realization of novel composites based on calcium sulphate blended with alginate and with a chemically modified chitosan, the synthesis of novel alginate-poly(ethylene glycol) copolymers and the development of a family of materials based on alginate and acrylic polymers of potential interest as drug delivery systems.     

Reactions of indoles with nitrogen dioxide and nitrous acid in an aprotic solvent

The reaction of 2-phenyl- and 1-methyl-2-phenylindole with nitrogen dioxide or with nitrous acid (NaNO2-CH3COOH) in benzene leads mainly to the formation of the isonitroso and 3-nitroso indole derivatives, respectively. When reacted with nitrous acid, 1-methyl-2-phenylindole gives also the corresponding azo-bis-indole in good yields. The reaction of indole with nitrogen dioxide leads to 2-(indol-3-yl)-3H-indol-3-one as the main product together with small amounts of 2-(indol-3-yl)-3H-indol-3-oxime; whereas the major product obtained when the same indole is reacted with nitrous acid is represented by 2-(indol-3-yl)-3H-indol-3-oxime. The reaction of 3-alkyl substituted indoles with nitrogen dioxide is rather complex and results in the formation of different nitro indoles, whereas nitrosation is observed when nitrous acid is used. Crystal structures of 2-(indol-3-yl)-3H-indol-3-one and of 4-nitro-N-acetyltryptamine have been determined by X-ray analysis.     

Applications of chiral C3-symmetric molecules

Throughout history symmetry and chirality have inspired artists and scientists alike. Given that rotational axes are the only elements of symmetry compatible with chirality, it is not surprising that C2- and C3-symmetrical molecules have attracted considerable attention. In recent years, the aesthetic appeal of C2-symmetrical molecules has been translated into many widely-used applications some of which are of commercial importance by its exploitation in the area of asymmetric catalysis. In contrast, exploitation of the arguably greater aesthetic appeal of C3-symmetric molecules is still in its infancy. This review, which surveys the applications of chiral C3-symmetrical molecules in the areas of asymmetric catalysis, molecular recognition and nanoarchitecture, has been designed with a view to identifying some of the most promising areas of application of these very beautiful molecules.     

Oligothiophene catenanes and knots. Part II. Mono and dications. A theoretical study

Mono- and dications of catenanes and knots containing 16, 22, and 28 thiophene units have been studied at the BHandHLYP/3-21G* level of theory. The polaron localization and relaxation energies of monoionized molecules increase with dihedral angle between thiophene fragments, being higher for catenanes and knots compared to linear oligomers. Monoionization of catenanes results in the polaron localization at one macrocycle leaving another one intact. In all diionized oligomers, polaron pairs were found to be more stable than corresponding bipolarons. The energy difference between bipolaron and polaron pairs increases with the number of repeating units in oligomers for all studied molecular architectures. Singlet polaron pairs are more stable than triplet ones. The energy difference between triplet and singlet states does not exceed 7-8 kcal/mol and decreases with the number of thiophene units in oligomers. Two different singlet minima were found for diionized catenanes. In the first one (the most stable), each macrocycle loses one electron, and in the other one, the polaron pairs are located at one macrocycle, leaving another intact. The energy difference between two minima decreases with the number of repeating units in catenanes.     

Isolation of three new naturally occurring compounds from the culture of Micromonospora sp. P1068

Bioassay guided isolation of an antibacterial extract prepared from the fermentation broth of a Micromonospora sp. P1068 led to the isolation of eight compounds identified as (3R) 3,4',7-trihydroxy-isoflavanone (1), 3-hydroxydehydrodaidzein, daidzein (2), 3-methyl-1H-indole-2-carboxylic acid (3), 1H-indole-3-carboxaldehyde (4), 3-(p-hydroxyphenyl)-N-methylpropionamide, N-methylphloretamide (5), phenyl acetic acid (6), 2-hydroxy phenyl acetic acid (7) and 4-hydroxy-5-methoxy-benzoic acid (8). Compounds 1 and 5 were found to be novel chemical entities while 3 was isolated from a natural source for the first time. All compounds were evaluated for their antimicrobial activities against a panel of clinically significant microorganisms. Compound 4 was active against Staphylococcus aureus (MIC, 32 microg/ml), Enterococcus faecium (MIC, 32 microg/ml) and Escherichia coli (MIC, 64 microg/ml).     

High-density lipoproteins contribute to the alpha-1-globulin zone in capillary electrophoresis of human serum proteins

Alpha-1-antitrypsin (AAT) and alpha-1-acid glycoprotein (AAG) are reported to be the main proteins contributing to the alpha-1-globulin capillary zone electrophoresis (CZE) zone, but the sum (AAT + AAG) showed lower than the alpha-1-globulin. We investigated the role of high-density lipoprotein (HDL), an additional protein migrating in the alpha-1-globulin zone, as a possible cause for such a gap. In a set of 98 sera we measured the alpha-1-globulin with a dedicated clinical capillary electrophoresis system, and AAT, AAG and apolipoprotein A-1 (ApoA) by immunonephelometry. The alpha-1-globulin were consistently higher than the sum (AAT + AAG), by (mean value +/- standard deviation) 1.70 +/- 0.88 g/L in 49 sera with low ApoA, and by 3.59 +/- 0.75 g/L in 49 sera with high ApoA. Corresponding figures in the comparison alpha-1-globulin/(AAT + AAG + ApoA) were reduced to 1.08 +/- 0.77 g/L and 1.67 +/- 0.70 g/L. It is concluded that HDL significantly contribute to the CZE alpha-1-globulin zone, but do not completely explain the differences between the electrophoretic and the immunochemical measurements. However, CZE alpha-1-globulin measurements give information about increases of the two major acute phase proteins comparable to specific protein measurements.     

Fungistatic activity of Zanthoxylum rhoifolium Lam. bark extracts against fungal plant pathogens and investigation on mechanism of action in Botrytis cinerea

Plant-derived compounds are emerging as an alternative choice to synthetic fungicides. Chloroform–methanol extract, obtained from the bark of Zanthoxylum rhoifolium, a member of Rutaceae, showed a fungistatic effect on Botrytis cinerea, Sclerotinia sclerotiorum, Alternaria alternata, Colletotrichum gloeosporioides and Clonostachys rosea, when added to the growth medium at different concentrations. A fraction obtained by gel separation and containing the alkaloid O-Methylcapaurine showed significant fungistatic effect against B. cinerea and S. sclerotiorum, two of the most destructive phytopathogenic fungi. The underlying mechanism of such an inhibition was further investigated in B. cinerea, a fungus highly prone to develop fungicide resistance, by analysing the expression levels of a set of genes (BcatrB, P450, CYP51 and TOR). O-Methylcapaurine inhibited the expression of all the analysed genes. In particular, the expression of BcatrB gene, encoding a membrane drug transporter involved in the resistance to a wide range of xenobiotic compounds, was strongly inhibited (91%).