Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids

Abstract A unified strategy for enantioselective total synthesis of all stereoisomers of the [2+2] family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either meso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a meso precursor or controlling diastereoselectivity in elaborating C2-symmetric intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+)- or (-)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine

Synthesis and Photoluminescence Properties of Porous Silicon Nanowire Arrays

Herein, we prepare vertical and single crystalline porous silicon nanowires (SiNWs) via a two-step metal-assisted electroless etching method. The porosity of the nanowires is restricted by etchant concentration, etching time and doping lever of the silicon wafer. The diffusion of silver ions could lead to the nucleation of silver nanoparticles on the nanowires and open new etching ways. Like porous silicon (PS), these porous nanowires also show excellent photoluminescence (PL) properties. The PL intensity increases with porosity, with an enhancement of about 100 times observed in our condition experiments. A “red-shift” of the PL peak is also found. Further studies prove that the PL spectrum should be decomposed into two elementary PL bands. The peak at 850 nm is the emission of the localized excitation in the nanoporous structure, while the 750-nm peak should be attributed to the surface-oxidized nanostructure. It could be confirmed from the Fourier transform infrared spectroscopy analyses. These porous SiNW arrays may be useful as the nanoscale optoelectronic devices

Nanofabrication with Pulsed Lasers

An overview of pulsed laser-assisted methods for nanofabrication, which are currently developed in our Institute (LP3), is presented. The methods compass a variety of possibilities for material nanostructuring offered by laser–matter interactions and imply either the nanostructuring of the laser-illuminated surface itself, as in cases of direct laser ablation or laser plasma-assisted treatment of semiconductors to form light-absorbing and light-emitting nano-architectures, as well as periodic nanoarrays, or laser-assisted production of nanoclusters and their controlled growth in gaseous or liquid medium to form nanostructured films or colloidal nanoparticles. Nanomaterials synthesized by laser-assisted methods have a variety of unique properties, not reproducible by any other route, and are of importance for photovoltaics, optoelectronics, biological sensing, imaging and therapeutics

Growth Strategies of Tropical Tree Species: Disentangling Light and Size Effects

An understanding of the drivers of tree growth at the species level is required to predict likely changes of carbon stocks and biodiversity when environmental conditions change. Especially in species-rich tropical forests, it is largely unknown how species differ in their response of growth to resource availability and individual size. We use a hierarchical Bayesian approach to quantify the impact of light availability and tree diameter on growth of 274 woody species in a 50-ha long-term forest census plot in Barro Colorado Island, Panama. Light reaching each individual tree was estimated from yearly vertical censuses of canopy density. The hierarchical Bayesian approach allowed accounting for different sources of error, such as negative growth observations, and including rare species correctly weighted by their abundance. All species grew faster at higher light. Exponents of a power function relating growth to light were mostly between 0 and 1. This indicates that nearly all species exhibit a decelerating increase of growth with light. In contrast, estimated growth rates at standardized conditions (5 cm dbh, 5% light) varied over a 9-fold range and reflect strong growth-strategy differentiation between the species. As a consequence, growth rankings of the species at low (2%) and high light (20%) were highly correlated. Rare species tended to grow faster and showed a greater sensitivity to light than abundant species. Overall, tree size was less important for growth than light and about half the species were predicted to grow faster in diameter when bigger or smaller, respectively. Together light availability and tree diameter only explained on average 12% of the variation in growth rates. Thus, other factors such as soil characteristics, herbivory, or pathogens may contribute considerably to shaping tree growth in the tropics

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%-15% yield from array CGH alone.Action Medical Research (SP4640); the Birth Defect Foundation (RG45448); the Cambridge National Institute for Health Research Biomedical Research Centre (RG64219); the NIHR Rare Diseases BioResource (RBAG163); Wellcome Trust award WT091310; The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases (member of the Telethon Network of Genetic Biobanks (project no. GTB12001); the Genetic Origins of Congenital Heart Disease Study (GO-CHD)- funded by British Heart Foundation (BHF)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/humu.2290

Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids

Abstract A unified strategy for enantioselective total synthesis of all stereoisomers of the [2+2] family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either meso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a meso precursor or controlling diastereoselectivity in elaborating C2-symmetric intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+)- or (-)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine