Olefin strain energy as a predictor of isolability

Data collection contains:Determination of the olefin stratin energy ranges corresponding to isolable, observable and unstable alkenes with contemporary forcefields - Bridgehead alkenes used to determine the olefin strain energy ranges corresponding to isolable, observable, and unstable  alkenes;Forcefield energies of alkenes S1-S25 and alkanes S1H2-S25H2;Olefin strain energies of alkenes S1-S25;Olefin strain energies of alkenes S1-S25 computed with different forcefields;Olefin strain energies of alkenes S1-S19 computed with different force fields, plotted against MM1 OS energy;Olefin strain energy calculations for natural products -Forcefield energies or bridgehead alkene natural products or putative bridgehead alkene natural products, and the  corresponding alkanes;Olefin strain energies of bridgehead alkene natural products or putative alkene natural products;OPLS_2005 Optimized geometries;Density Functional Theory (DFT) calculations -DFT calculations on NP's giving a measure of the amount of strain energy not captured by the forcefield;B3LYP-D3 optimized geometries and associated energies;A small set of alkenes for rapid estimation of OS cutoffs for other forcefield

The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-D-glucuronides to L-iduronides are dependent on the anomeric substituent: syntheses and DFT calculations

One of the shortest synthetic routes to L-iduronic acid derivatives is via free radical reduction of the C-5 bromide of the corresponding protected D-glucuronic acid derivative. The epimerization of such C-5 bromides to the L-ido derivatives via reaction with tributyltin hydride was investigated. It was found that the stereoselectivity of the reaction was dependent on the anomeric substituent. If the substituent was fluoride the L-ido product was obtained exclusively in 65-72% yield whereas the O-methyl or O-acetyl derivatives led to isomeric mixtures of both the L-ido and D-gluco products in different ratios depending on the reaction conditions. DFT calculations were performed to determine the stereoelectronic factors that favour formation of the L-ido isomer from the fluoride and suggest the selectivity is due to a transition state gauche effect and an Sn-F interaction

Rearrangement-free hydroxylation of methylcubanes by a cytochrome P450: the case for dynamical coupling of C-H abstraction and rebound

The highly strained cubylmethyl radical undergoes one of the fastest radical rearrangements known (reported k = 2.9 × 1010 s-1 at 25 °C) through scission of two bonds of the cube. The rearrangement has previously been used as a mechanistic probe to detect radical-based pathways in enzyme-catalyzed C-H oxidations. This paper reports the discovery of highly selective cytochrome P450-catalyzed methylcubane oxidations which notionally proceed via cubylmethyl radical intermediates yet are remarkably free of rearrangement. The bacterial cytochrome P450 CYP101B1 from Novosphingobium aromaticivorans DSM 12444 is found to hydroxylate the methyl group of a range of methylcubane substrates containing a regio-directing carbonyl functionality at C-4. Unlike other reported P450-catalyzed methylcubane oxidations, the designed methylcubanes are hydroxylated with high efficiency and selectivity, giving cubylmethanols in yields of up to 93%. The lack of cubane core ring-opening implies that the cubylmethyl radicals formed during these CYP101B1-catalyzed hydroxylations must have very short lifetimes, of just a few picoseconds, which are too short for them to manifest the side reactivity characteristic of a fully equilibrated P450 intermediate. We propose that the apparent ultrafast radical rebound can be explained by a mechanism in which C-H abstraction and C-O bond formation are merged into a dynamically coupled process, effectively bypassing a discrete radical intermediate. Related dynamical phenomena can be proposed to predict how P450s may achieve various other modes of reactivity by controlling the formation and fate of radical intermediates. In principle, dynamical ideas and two-state reactivity are each individually able to explain apparent ultrashort radical lifetimes in P450 catalysis, but they are best considered together.Md. Raihan Sarkar, Sevan D. Houston, G. Paul Savage, Craig M. Williams, Elizabeth H. Krenske, Stephen G. Bell and James J. De Vos

Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort

STUDY FUNDING The data were collected by a Research into Ageing programme grant; research continues as part of the Age UK–funded Disconnected Mind project. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1), with funding from the BBSRC and Medical Research Council. Imaging and image analysis was performed at the Brain Research Imaging Centre (sbirc.ed.ac.uk/), Edinburgh, supported by the Scottish Funding Council SINAPSE Collaboration. Derivation of mean cortical thickness measures was funded by the Scottish Funding Council’s Postdoctoral and Early Career Researchers Exchange Fund awarded by SINAPSE to David Alexander Dickie. L.C.A.C. acknowledges funding from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) division.Peer reviewedPublisher PD

1,4‐Dithiane‐2,5‐diol: An Attractive Platform for the Synthesis of Sulfur Containing Functionalized Heterocycles

This microreview highlights the utility of 1,4? dithiane?2,5?diol 1 as a source for the in situ generation of 2?mercaptoacetaldehyde 2, a versatile two?carbon synthon featuring both electrophilic and nucleophilic reaction centers widely utilized as an attractive platform for the preparation of sulfur?containing molecules. We discussed the involved chemistry, mainly focusing on its applications to the construction of sulfur?containing heterocyclic compounds including the thiophene and 1,3?thiazole families and other different sulfur?nitrogen and sulfur?oxygen heterocycles which continue to be a pillar of organic synthesis as a result of their broad application in organic and medicinal chemistry

Aromatic interactions in asymmetric catalysis: control of enantioselectivity in Diels-Alder reactions catalysed by camphor-derived hydrazides

Density functional theory calculations (M06-2X//B3LYP) have been performed to determine the factors responsible for enantioselectivity in Diels-Alder reactions catalysed by two series of camphor-derived amines. Hydrazides 2 and sulfonylhydrazides 3 catalyze the reaction of cyclopentadiene with cinnamaldehyde to give the same enantiomer of cycloadduct. The calculations reveal that the two classes of catalysts control enantioselectivity by opposite mechanisms. Hydrazides 2 favour addition to the bottom face of a trans iminium cation, while sulfonylhydrazides 3 favour addition to the top face of a cis iminium ion. In the transition state for cycloadditions catalysed by 2, a stabilising CH-π interaction between the diene and a benzyl substituent α to the iminium nitrogen accelerates the reaction and enhances the enantioselectivity. The facial selectivity can be reinforced by appending onto the benzyl side-arm an α-methyl group that sterically hinders addition to the top face

Synthesis, characterization and complexation studies of a cage ligand bearing a tris(bipyridyl)iron(II) capping group

Reaction between 5-(4-amino-2-thiabutyl)-5-methyl-3,7-dithianonane-1,9-diamine (N3S3) and 5-methyl-2,2-bipyridine-5-carbaldehyde and subsequent reduction of the resulting imine with sodium borohydride results in a potentially ditopic ligand (L). Treatment of L with one equivalent of an iron(II) salt led to the monoprotonated complex [Fe(HL)], isolated as the hexafluorophosphate salt. The presence of characteristic bands for the tris(bipyridyl)iron(II) chromophore in the UV/vis spectrum indicated that the iron(II) atom is coordinated octahedrally by the three bipyridyl (bipy) groups. The [Fe(bipy)] moiety encloses a cavity composed of the N3S3 portion of the ditopic ligand. The mononuclear and monomeric nature of the complex [Fe(HL)] has been established also by accurate mass analysis. [Fe(HL)] displays reduced stability to base compared with the complex [Fe(bipy)]. In aqueous solution [Fe(HL)] exhibits irreversible electrochemical behaviour with an oxidation wave ca. 60 mV to more positive potential than [Fe(bipy)]. Investigations of the interaction of [Fe(L)] with copper(II), iron(II), and mercury(II) using mass spectroscopic and potentiometric methods suggested that where complexation occurred, fewer than six of the N3S3 cavity donors were involved. The high affinity of the complex [Fe(L)] for protons is one reason suggested to contribute to the reluctance to coordinate a second metal ion