Synthetic studies toward the brasilinolides: controlled assembly of a protected C1-C38 polyol based on fragment union by complex aldol reactions.

The brasilinolides are an architecturally complex family of 32-membered macrolides, characterised by potent immunosuppressant and antifungal properties, which represent challenging synthetic targets. By adopting a highly convergent strategy, a range of asymmetric aldol/reduction sequences and catalytic protocols were employed to assemble a series of increasingly elaborate fragments. The controlled preparation of suitable C1-C19 and C20-C38 acyclic fragments 5 and 6, containing seven and 12 stereocentres respectively, was first achieved. An adventurous C19-C20 fragment union was then explored to construct the entire carbon chain of the brasilinolides. This pivotal coupling step could be performed in a complex boron-mediated aldol reaction to install the required C19 hydroxyl stereocentre when alternative Mukaiyama-type aldol protocols proved unrewarding. A protected C1-C38 polyol 93 was subsequently prepared, setting the stage for future late-stage diversification toward the various brasilinolide congeners. Throughout this work, asymmetric boron-mediated aldol reactions of chiral ketones with aldehydes proved effective both for controlled fragment assembly and coupling with predictable stereoinduction from the enolate component.We thank the EPSRC (EP/F025734/1) and Syngenta for support, the Isaac Newton–Mays Wild Research Fellowship at Downing College (M.P.H.), the Herchel Smith Postdoctoral Fellowships Fund at Cambridge (C.J.C.) and the Deutsche Akademie der Naturforser Leopoldina (F.A.M.; BMBF-LPD 9901/8-148) for additional funding, and the EPSRC National Mass Spectrometry Centre (Swansea) for mass spectra.This is the final published version of the article. It was originally published in Organic & Biomolecular Chemistry (Paterson I, Housden MP, Cordier CJ, Burton PM, Mühlthau FA, Loiseleur O, Organic & Biomolecular Chemistry, 2015,13, 5716-5733 doi:10.1039/C5OB00498E). The final version is available at http://dx.doi.org/10.1039/C5OB00498

Parallel declines in species and genetic diversity driven by anthropogenic disturbance: a multispecies approach in a French Atlantic dune system.

Numerous studies assess the correlation between genetic and species diversities, but the processes underlying the observed patterns have only received limited attention. For instance, varying levels of habitat disturbance across a region may locally reduce both diversities due to extinctions, and increased genetic drift during population bottlenecks and founder events. We investigated the regional distribution of genetic and species diversities of a coastal sand dune plant community along 240 kilometers of coastline with the aim to test for a correlation between the two diversity levels. We further quantify and tease apart the respective contributions of natural and anthropogenic disturbance factors to the observed patterns. We detected significant positive correlation between both variables. We further revealed a negative impact of urbanization: Sites with a high amount of recreational infrastructure within 10 km coastline had significantly lowered genetic and species diversities. On the other hand, a measure of natural habitat disturbance had no effect. This study shows that parallel variation of genetic and species diversities across a region can be traced back to human landscape alteration, provides arguments for a more resolute dune protection, and may help to design priority conservation areas

Techniques de laboratoire

Contén: t. I. Chimie physique. Chimie biologique (930 p.) -- t. II. Chimie clinique (444 p.

Détermination de la solubilité du tétrahydrothiophène (THT) liquide dans les principaux constituants du gaz naturel (CH

Certains produits comme le tétrahydrothiophène (THT), dont l'odeur est perçue à faible teneur, sont injectés dans le gaz naturel en vue de son odorisation. Cette odorisation artificielle rend toute fuite éventuelle de gaz dans l'atmosphère immédiatement détectable. Les auteurs ont mesuré les compositions à l'équilibre des phases gaseuses des binaires THT-CH4, THT-N02 et THT-CO2 dans les conditions de transport et de distribution du gaz [ 1 < P (bar) < 60 and -30 < t(○C) < 50] . Dans ce but, un dispositif expérimental original basé sur un principe de saturation dynamique avec analyse chromatographique en ligne de la phase vapeur a été réalisé et mis au point. Des grandeurs thermodynamiques supplémentaires sont nécessaires pour atteindre les compositions molaires de la phase vapeur. Les auteurs ont mesuré les pressions de vapeur du THT et estimé les seconds coefficients du viriel. Ces estimations font intervenir les grandeurs critiques et facteurs acentriques qui ont été calculés par diverses corrélations

The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments.

Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. A C1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid