Catalyst-Controlled Stereoselective Barton-Kellogg Olefination

Overcrowded alkenes are expeditiously prepared by the versatile Barton-Kellogg olefination and have remarkable applications as functional molecules endowed by their unique stereochemical features. The induced stereodynamics thereby enable the controlled motion of molecular switches and motors while the high configurational stability prevents undesired isomeric scrambling that would impact their essential molecular topology. Bistricyclic aromatic enes are prototypical overcrowded alkenes with outstanding stereochemical properties, but their stereocontrolled preparation is challenging and was thus far only feasible in stereospecific reactions and by the use of chiral auxiliaries. Here, we now report that direct catalyst control is achieved by means of a stereoselective Barton-Kellogg olefination with enantio- and diastereocontrol in the preparation of various bistricyclic aromatic enes. Using Rh2(S-PTAD)4 as catalyst, several diazo compounds were selectively coupled with a thioketone to give one of the four anti -folded overcrowded alkene stereoisomers upon reduction. Moreover, complete stereodivergence was reached by catalyst control in combination with distinct thiirane reductions, providing access to all four stereoisomers with an e.r. of up to 99:1. We envision that the catalyst controlled synthesis of overcrowded alkenes and the possibility for stereodivergence in the Barton-Kellogg olefination will provide a direct and effective route for a broad range of topologically unique overcrowded alkenes for functional molecules, catalysis, energy- and electron transfer, or bioactive compounds

Photocatalytic deracemisation of cobalt(III) complexes with fourfold stereogenicity

The deracemisation of fourfold stereogenic cobalt(III) diketonates with a chiral photocatalyst is described. With only 0.5 mol% menthyl Ru(bpy); 3; 2+; photocatalyst, an enantiomeric enrichment of up to 88 : 12 e.r. was obtained for the major meridional diastereomers. Moreover, a distribution of configurationally stable diastereomers distinct from the thermodynamic ratio was observed upon reaching the photostationary state

Catalyst Repurposing Sequential Catalysis by Harnessing Regenerated Prolinamide Organocatalysts as Transfer Hydrogenation Ligands

A catalyst repurposing strategy based on a sequential aldol addition and transfer hydrogenation giving access to enantiomerically enriched α-hydroxy-γ-butyrolactones is described. The combination of a stereoselective, organocatalytic step, followed by an efficient catalytic aldehyde reduction induces an ensuing lactonization to provide enantioenriched butyrolactones from readily available starting materials. By capitalizing from the capacity of prolineamides to act as both an organocatalyst and a transfer hydrogenation ligand, catalyst repurposing allowed the development of an operationally simple, economic, and efficient sequential catalysis approach

A study of the validity of the Keystone color vision cards as a screening device for color defectives

A study of the validity of the Keystone color vision cards as a screening device for color defective

First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

Insights from birthing experiences of fistula survivors in North-central Nigeria: Interplay of structural violence

Obstetric Fistula is an abnormal opening between the vagina and rectum resulting from prolonged and obstructed labour. Studies indicate that delays in accessing maternal care and home birth contribute to the development of fistula. Survivors are usually women of low socioeconomic status residing in rural locations. This study explores the birthing experiences of 15 fistula survivors through a narrative inquiry approach at a repair centre in North-central Nigeria. Using structural violence as a lens, it describes the role of social, political and health systems in the inequitable access to care for women. For women opting for home births, preference for home delivery was mainly due to lack of finances, poor health systems and cultural practices. Rural location inhibited access as, women seeking facility delivery faced transfer delays to referral centres when complications developed. Inequitable maternal health services in rural locations in Nigeria are inherently linked to access to health care; and these contribute to the increased incidences of fistulae. Structural intervention is a health policy priority to address poor health systems and achieve universal health coverage to address maternal health issues in Nigeria

The role of the disulfide bond in the interaction of islet amyloid polypeptide with membranes

Human islet amyloid polypeptide (hIAPP) forms amyloid fibrils in pancreatic islets of patients with type 2 diabetes mellitus. It has been suggested that the N-terminal part, which contains a conserved intramolecular disulfide bond between residues 2 and 7, interacts with membranes, ultimately leading to membrane damage and β-cell death. Here, we used variants of the hIAPP1–19 fragment and model membranes of phosphatidylcholine and phosphatidylserine (7:3, molar ratio) to examine the role of this disulfide in membrane interactions. We found that the disulfide bond has a minor effect on membrane insertion properties and peptide conformational behavior, as studied by monolayer techniques, 2H NMR, ThT-fluorescence, membrane leakage, and CD spectroscopy. The results suggest that the disulfide bond does not play a significant role in hIAPP–membrane interactions. Hence, the fact that this bond is conserved is most likely related exclusively to the biological activity of IAPP as a hormone

Point Mutations in Aβ Result in the Formation of Distinct Polymorphic Aggregates in the Presence of Lipid Bilayers

A hallmark of Alzheimer's disease (AD) is the rearrangement of the β-amyloid (Aβ) peptide to a non-native conformation that promotes the formation of toxic, nanoscale aggregates. Recent studies have pointed to the role of sample preparation in creating polymorphic fibrillar species. One of many potential pathways for Aβ toxicity may be modulation of lipid membrane function on cellular surfaces. There are several mutations clustered around the central hydrophobic core of Aβ near the α-secretase cleavage site (E22G Arctic mutation, E22K Italian mutation, D23N Iowa mutation, and A21G Flemish mutation). These point mutations are associated with hereditary diseases ranging from almost pure cerebral amyloid angiopathy (CAA) to typical Alzheimer's disease pathology with plaques and tangles. We investigated how these point mutations alter Aβ aggregation in the presence of supported lipid membranes comprised of total brain lipid extract. Brain lipid extract bilayers were used as a physiologically relevant model of a neuronal cell surface. Intact lipid bilayers were exposed to predominantly monomeric preparations of Wild Type or different mutant forms of Aβ, and atomic force microscopy was used to monitor aggregate formation and morphology as well as bilayer integrity over a 12 hour period. The goal of this study was to determine how point mutations in Aβ, which alter peptide charge and hydrophobic character, influence interactions between Aβ and the lipid surface. While fibril morphology did not appear to be significantly altered when mutants were prepped similarly and incubated under free solution conditions, aggregation in the lipid membranes resulted in a variety of polymorphic aggregates in a mutation dependent manner. The mutant peptides also had a variable ability to disrupt bilayer integrity