Functionalized Templates for the Convergent Assembly of Polyethers: Synthesis of the HIJK Rings of Gymnocin A

Extension ladder: The successful application of epoxide-opening strategies towards the synthesis of ladder-type polyethers is contingent upon further elaboration of the product. By employing two different functionalized templates, a fragment of gymnocin A that bears four sites for subsequent fragment coupling has been prepared (see scheme; Bn=benzyl).National Institute of General Medical Sciences (U.S.) (GM72566)Wyeth Research (Fellowship

A Comparative Structural Study in Monolayers of GPI Fragments and Their Binary Mixtures

Glycosylphosphatidylinositols (GPIs), natural complex glycolipids essential for a range of biological functions, are poorly understood with regard to their interactions and arrangements in cellular membranes. To evaluate the role of the head group in the structure formation in 2D model membranes (monolayers formed at the soft air/liquid interface), we employed the highly surface sensitive grazing incidence X-ray diffraction technique to investigate three GPI-fragments bearing the same hydrophobic part but different head groups. Condensed monolayers of simple GPI fragments are defined only by ordered alkyl chains. The monolayers of more complex fragments are additionally characterized by highly ordered head groups. Due to the strong H-bond network formed by the head groups, GPI-fragment 3 both segregates and induces order into a model membrane phospholipid (POPC) that mimics the liquid-disordered phase of cell membranes. Here, we show that the strong van der Waals interactions between hydrophobic chains overcome the head group interactions and dominate the structure formation in mixtures of GPI-fragment 3 with lipids that form liquid-condensed phases. This behaviour can be linked to the GPIs affinity for the lipid rafts

The development of endo-selective epoxide-opening cascades in water

This tutorial review traces the development of endo-regioselective epoxide-opening reactions in water. Templated, water-promoted epoxide-opening cyclization reactions can offer rapid access to subunits of the ladder polyethers, a fascinating and complex family of natural products. This review may be of interest to those curious about the ladder polyethers and their hypothesized biogenesis, about organic reactions in water, and about the development and application of cascade reactions in organic synthesis

The effect of covert visual attention on pupil size during perceptual fading

Pupil size is modulated by various cognitive factors such as attention, working memory, mental imagery, and subjective perception. Previous studies examining cognitive effects on pupil size mainly focused on inducing or enhancing a subjective experience of brightness or darkness (for example by asking participants to attend to/memorize a bright or dark stimulus), and then showing that this affects pupil size. Surprisingly, the inverse has never been done; that is, it is still unknown what happens when a subjective experience of brightness or darkness is eliminated or strongly reduced even though bright or dark stimuli are physically present. Here, we aim to answer this question by using perceptual fading, a phenomenon where a visual stimulus gradually fades from visual awareness despite its continuous presentation. The study contains two blocks: Fading and Non-Fading. In the Fading block, participants were presented with black and white patches with a fuzzy outline that were presented at the same location throughout the block, thus inducing strong perceptual fading. In contrast, in the Non-Fading block, the patches switched sides on each trial, thus preventing perceptual fading. Participants covertly attended to one of the two patches, indicated by a cue, and reported the offset of one of a set of circles that are displayed on top. We hypothesized that pupil size will be modulated by covert visual attention in the Non-Fading block, but that this effect will not (or to a lesser extent) arise in the Fading block. We found that covert visual attention to bright/dark does modulate pupil size even during perceptual fading (Fading block), but to a lesser extent than when the perceptual experience of brightness/darkness is preserved (Non-Fading block). This implies that pupil size is always modulated by covert attention, but that the effect decreases as subjective experience of brightness or darkness decreases. In broader terms, this suggests that cognitive modulations of pupil size reflect a mixture of high-level and lower-level visual processing

Methods in cognitive pupillometry:Design, preprocessing, and statistical analysis

Cognitive pupillometry is the measurement of pupil size to investigate cognitive processes such as attention, mental effort, working memory, and many others. Currently, there is no commonly agreed-upon methodology for conducting cognitive-pupillometry experiments, and approaches vary widely between research groups and even between different experiments from the same group. This lack of consensus makes it difficult to know which factors to consider when conducting a cognitive-pupillometry experiment. Here we provide a comprehensive, hands-on guide to methods in cognitive pupillometry, with a focus on trial-based experiments in which the measure of interest is the task-evoked pupil response to a stimulus. We cover all methodological aspects of cognitive pupillometry: experimental design, preprocessing of pupil-size data, and statistical techniques to deal with multiple comparisons when testing pupil-size data. In addition, we provide code and toolboxes (in Python) for preprocessing and statistical analysis, and we illustrate all aspects of the proposed workflow through an example experiment and example scripts.</p

Transition‐Metal‐Free Alkylation of N‐Heterocycles with Nitriles via Heteroarylphosphonium Intermediates

Heteroarylphosphonium salts are easily accessible, versatile intermediates in functionalization of N‐heterocycles. Direct C−C bond formation by net substitution of the phosphine has so far required transition metal catalysts, the use of strongly basic reagents or redox catalysis. Here we describe a C−C bond formation in direct reactions of benzothiazol‐2‐yl‐phosphonium and pyridin‐4‐yl‐phosphonium salts and nitrile anions which, together with the direct synthesis of phosphonium salts from benzothiazoles and pyridines, constitutes an efficient and simple two‐step protocol for C−H functionalization of these heterocycles under mild conditions

Synthesis of β‐Amino Acid Derivatives via Enantioselective Lewis Base Catalyzed N‐Allylation of Halogenated Amides with Morita‐Baylis‐Hillman Carbonates

Trifluoro‐ and trichloroacetamides serving as pronucleophiles undergo enantioselective Lewis base catalyzed N ‐allylation with Morita‐Baylis‐Hillman carbonates to produce enantioenriched β‐amino acid derivatives. The reactions proceed as a kinetic resolution to give the allylation products and the remaining carbonates in good yields and high enantioselectivity. The obtained products are amenable to diastereoselective derivatization to produce a library of spiro‐isoxazoline lactams

Latent Pronucleophiles in Lewis Base Catalysis: Enantioselective Allylation of Silyl Enol Ethers with Allylic Fluorides

Lewis base catalyzed allylations of C‐centered nucleophiles have been largely limited to the niche substrates with acidic C−H substituted for C−F bonds at the stabilized carbanionic carbon. Herein we report that the concept of latent pronucleophiles serves to overcome these limitations and allow for a variety of common stabilized C‐nucleophiles, when they are introduced as the corresponding silylated compounds, to undergo enantioselective allylations using allylic fluorides. The reactions of silyl enol ethers afford the allylation products in good yields and with high degree of regio/stereoselectivity as well as diastereoselectivity when cyclic silyl enol ethers are used. Further examples of silylated stabilized carbon nucleophiles that undergo efficient allylation speak in favor of the general applicability of this concept to C‐centered nucleophiles