Octagon-Embedded Carbohelicene as a Chiral Motif for Circularly Polarized Luminescence Emission of Saddle-Helix Nanographenes.

We report a new family of hexa-peri-hexabenzocoronene (HBC)-based helical nanographenes incorporating π-extended carbo[5]helicenes bearing an octagonal carbocycle. This family represents a new kind of highly distorted saddle-helix hybrid nanographenes. For the first time, the eight-membered ring becomes a constituent of both a carbo[5]helicene and a HBC and thus, the negative curvature is responsible for twisting both units. This novel chiral motif, namely, oct-[5]helicene results in the largest torsion angle recorded so far for a carbo[5]helicene (θ=79.5°), as it has been suggested by DFT-calculations and confirmed by X-ray crystallography. Consequently, the barriers of isomerization become exceptionally high for a [5]helicene unsubstituted in the fjord region since neither racemization nor decomposition were observed at 200 °C for 1 or 3 during 5 h. Therefore, racemic resolutions allowed subsequent chiroptical studies showing the ECD and CPL responses of this novel family of chiral nanographenes.

Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection.

Although certain microbial lipids are toxins, the structural features important for cytotoxicity remain unknown. Increased functional understanding is essential for developing therapeutics against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented, cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of GBS disease, studies towards understanding granadaene's toxic activity are hindered by its instability and insolubility in purified form. Here, we report the synthesis and screening of lipid derivatives inspired by granadaene, which reveal features central to toxin function, namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic synthetic analog confers the production of antibodies that inhibit granadaene-mediated hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural and functional insight into granadaene and a strategy to mitigate GBS infection, which will be relevant to other toxic lipids encoded by human pathogens.

Direct determination of phenolic secoiridoids in olive oil by ultra-high performance liquid chromatography-triple quadruple mass spectrometry analysis.

In recent years, a large number of biological properties and an important role in the organoleptic characteristics of olive oil have been attributed to phenolic secoiridoids, such as oleacein, oleocanthal, oleuropein aglycone and ligstroside aglycone. Consequently, quantifying them is of great interest for the olive oil sector. Currently, there is no consensus in which analytical method must be use to accurately determine these compounds in olive oil, mainly owing to the lack of reference standards for calibration. In this work, analytical standards of phenolic secoiridoids have been used to develop a quantitative and rapid analytical method by UHPLC-MS/MS, in which sample extraction is not carried out. Simple dilutions of the sample with dry tetrahydrofuran and dry acetonitrile were performed before analysing them. It is worth noting that under these conditions the generation of artefacts such as acetals and hemiacetals of the aldehydic forms is highly reduced. The detection and quantification was performed with a Xevo TQS tandem quadrupole mass spectrometer. The method was validated at four concentration levels and finally applied to six samples of extra virgin olive oil.

Quantification of oleacein and oleuropein aglycone in olive oil using deuterated surrogates by normal-phase ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

An analytical method for the analysis of relevant secoiridoid-based components in olive oil, oleacein and oleuropein aglycone, is described using for the first time deuterated surrogates. 0.2 g of sample was necessary to perform the analysis using liquid-liquid extraction and ultrasound-assisted extraction with a mixture of methanol/water (4:1, v/v). To avoid the formation of by-products, normal-phase ultra high performance liquid chromatography was chosen for the chromatographic separation. The selected mobile phase was a gradient mixture of tetrahydrofurane and hexane, and an ACE Excel 3 CN-ES column as stationary phase. The detection and quantification was performed with a SYNAPT G2-Si mass spectrometer. The calibration curves for oleacein and oleuropein aglycone were linear and quadratic, respectively. The validation was done at three levels of concentration. Relative errors from 0.1 to 10.5% and relative standard deviations lower than 9% were obtained. The method was applied to study different samples of olive oil.

Aggregation-induced emission of [3]cumulenes functionalized with heptagon-containing polyphenylenes.

Turning on the fluorescence of [3]cumulenes: we report the luminescence at room temperature upon aggregation of [3]cumulenes functionalized with propeller-like heptagon-containing polyphenylenes. These endgroups turn on the emission of a [3]cumulene by steric protection and restriction of their intramolecular rotations in the aggregates.

Antiproliferative Activity of Natural Taiwaniaquinoids and Related Compounds.

The in vitro antiproliferative activities of some taiwaniaquinoids and related compounds with functionalized A, B, or C rings against human breast (MCF-7), colon (T-84), and lung (A-549) tumor cell lines were assayed. The most potent compounds, 16, 27, and 36, were more effective than the naturally occurring taiwaniaquinones A (4) and F (5) in all three cell lines. The structure-activity relationship study of these new taiwaniaquinoids highlighted the correlation between the bromo substituent and the antiproliferative activity, especially in MCF-7 cells. These findings indicate that some of the taiwaniaquinoids might be useful as cytostatic agents against breast, colon, and lung cancer cell lines.

Stereoselective transformations of (+)-abietic acid into (+)-vitedoin B and (+)-negundoin A.

The first synthesis of spirolactone (+)-vitedoin B (14 steps, 8.0% global yield) and spiro enol ether (+)-negundoin A (19 steps, 3.7% global yield), via a nor-labdane acetoxy ester, has been achieved starting from commercial (+)-abietic acid.

The first synthesis of (-)-isoambreinolide, (+)-vitexifolin D and (+)-vitedoin B.

A very efficient method for synthesizing spirolactones is reported. Treatment of δ,ε-unsaturated carboxylic acids with iodine and triphenylphosphine under mild conditions leads to the corresponding spiro γ-lactones in high yield and with complete stereoselectivity. Utilizing this, the first synthesis of the terpene spirolactones (-)-isoambreinolide, (+)-vitexifolin D and (+)-vitedoin B has been achieved.

I2-PPh3 mediated spiroannulation of unsaturated ß-dicarbonyl compounds. The first synthesis of (±)-negundoin A.

An efficient and stereoselective spiroannulation of unsaturated enols is reported. Unsaturated ß-dicarbonyl compounds undergo cyclization by reaction with catalytic I2-PPh3, affording the corresponding spiro enol ether derivatives, with complete regio- and stereoselectivity, under mild conditions. Utilizing this new methodology, the first total synthesis of the anti-inflammatory diterpene negundoin A and a naturally occurring trypanocidal aldehyde is reported.

NIS-PPh3: a selective reagent for the spiroannulation of o-allyl phenols. Total synthesis of corallidictyal D.

Treatment of o-allyl phenols with catalytic NIS-PPh3 affords the corresponding spirodihydrobenzofuran derivatives in high yield with high regio- and total stereoselectivity under mild conditions. These results were utilized to achieve the first total synthesis of the protein kinase C inhibitor corallidictyal D starting from α-ionone.

General access to taiwaniaquinoids based on a hypothetical abietane C7-C8 cleavage biogenetic pathway.

A new strategy for synthesizing taiwaniaquinoids, a group of terpenoids with an unusual rearranged 5(6→7) or 6-nor-5(6→7)abeo-abietane skeleton, which exhibit promising biological activities, is reported. The procedure, based on the cleavage of the C7-C8 double bond of abietane diterpenes, is the only one yet reported for synthesizing C(20) taiwaniaquinoids bearing a carbon function on the cyclopentane B ring; it is also applicable to the synthesis of the wide variety of existing taiwaniaquinoids. Utilizing this, (-)-taiwaniaquinone A, F, G, and H, (-)-taiwaniaquinol B, and (-)-dichroanone have been synthesized from (+)-abietic acid. The versatility of this strategy allows us to propose the abietane C7-C8 cleavage as a possible biosynthetic pathway to this type of rearranged diterpenes; this proposal seems to be supported by phytochemical evidence.

Enantioselective total synthesis of cytotoxic taiwaniaquinones A and F.

The first synthesis of cytotoxic (-)-taiwaniaquinone A and (-)-taiwaniaquinone F has been achieved through the intramolecular aldol condensation of a ketoaldehyde and the oxidative cleavage of an isopropylidene ketal.

Childhood immunization rates in Louisiana: trends from 1995-2004.

Immunization is an invaluable tool in preventing the morbidity and mortality associated with many infectious diseases. The CDC currently recommends that children obtain immunizations against 11 diseases. We examined immunization rates in Louisiana children aged 19-35 months from 1995-2003 and compared these rates with the rates in neighboring states and the national coverage rate. Coverage rates were affected by the number of vaccinations in a series and the year of life at which the vaccines are received. We also found discrepancies in coverage rates of immunizations that should be given simultaneously. While Louisiana coverage rates have improved after a dip in 2001, we suggest steps to help physicians further improve coverage rates.

A review of varicella vaccine and Louisiana vaccination requirements.

In order to decrease the burden of disease from varicella and increase varicella vaccination rates nationally, all states were advised by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention in May 1999 to institute vaccination requirements or documented evidence of natural infection for all children entering elementary school and daycare facilities. Beginning September 1, 2003, Louisiana law requires varicella vaccination or a history of varicella disease prior to entry to school and daycare. In light of these new state requirements, this article discusses the epidemiology of varicella and addresses a number of concerns about the varicella vaccine. The four main issues addressed via a literature review are (1) the perception of varicella as a benign childhood disease, (2) concerns about vaccine efficacy and safety, (3) concerns about waning immunity, and (4) concerns about shifting burden of disease. The article also reviews varicella vaccination recommendations and encourages vaccination of all children in accordance with new state requirements.