Synthesis of fused cyclic systems containing medium-sized rings through tandem ROM-RCM of norbornene derivatives embedded in a carbohydrate template

A general approach for the synthesis of fused cyclic systems containing medium-sized rings (7-9) has been developed. The key steps involve a diastereoface-selective Diels-Alder reaction of the dienophiles 4a-d attached to a furanosugar with cyclopentadiene and ring opening (ROM)-ring closing metathesis (RCM) of the resulting norbornene derivatives 10a-d and 11a-d. Diels-Alder reaction of the dienophiles 4a-d with cyclopentadiene in the absence of a catalyst produced 10a-d as the major product arising through addition of the diene to the unhindered Si-face. The most interesting and new aspect of the Diels-Alder reaction of these dienophiles is the accessibility of the Re-face that was blocked by the alkenyl chains under Lewis acid catalysis producing the diastereoisomers 11a-d exclusively. The reversal of facial selectivity from an uncatalyzed reaction to a catalyzed one is unprecedented. The observed stereochemical dichotomy is attributed to rotation of the enone moiety along the or bond linking the sugar moiety during formation of the chelate 13. This makes the Re-face of the enone moiety in 4a-d unhindered. Diels-Alder reaction of the carbocyclic analogue 15 under Lewis acid catalysis produced a 1: 1 mixture of the adducts 16 and 17 confirming the participation of sugar ring oxygen in chelate formation. Finally ROM-RCM of 10a-d and 11a-d with Grubbs' catalyst afforded the cis-syn-cis and cis-anti-cis bicyclo-annulated sugars 21a-d and 23a-d, respectively, containing 7-9 membered rings.

Occurrence of ribbons of cyclic water pentamers in a metallo-organic framework formed by spontaneous fixation of CO2

In the reaction of equimolar amounts of copper(II) acetate with 2,2'-dipyridylamine (DPA) in aqueous tetrahydrofuran, in presence of KOH, aerial CO2 is spontaneously fixed to the carbonate anion yielding [Cu(DPA)(CO3)] . 3H(2)O (1). X-ray crystallography shows the presence of zigzag ribbons of cyclic water pentamers in the channels of a chain-like metallo-organic framework. The water ribbons are stabilised by hydrogen bonds to the metallo-organic backbone. Each (H2O)(5) pentamer is approximately planar.

Designs for an adaptive tuned vibration absorber with variable shape stiffness element

An adaptive tuned vibration absorber (ATVA) with a smart variable stiffness element is capable of retuning itself in response to a time-varying excitation frequency., enabling effective vibration control over a range of frequencies. This paper discusses novel methods of achieving variable stiffness in an ATVA by changing shape, as inspired by biological paradigms. It is shown that considerable variation in the tuned frequency can be achieved by actuating a shape change, provided that this is within the limits of the actuator. A feasible design for such an ATVA is one in which the device offers low resistance to the required shape change actuation while not being restricted to low values of the effective stiffness of the vibration absorber. Three such original designs are identified: (i) A pinned-pinned arch beam with fixed profile of slight curvature and variable preload through an adjustable natural curvature; (ii) a vibration absorber with a stiffness element formed from parallel curved beams of adjustable curvature vibrating longitudinally; (iii) a vibration absorber with a variable geometry linkage as stiffness element. The experimental results from demonstrators based on two of these designs show good correlation with the theory.

Finite element aided design evolution of composite leaf spring

This paper shows the process of the virtual production development of the mechanical connection between the top leaf of a dual composite leaf spring system to a shackle using finite element methods. The commercial FEA package MSC/MARC has been used for the analysis. In the original design the joint was based on a closed eye-end. Full scale testing results showed that this configuration achieved the vertical proof load of 150 kN and 1 million cycles of fatigue load. However, a problem with delamination occurred at the interface between the fibres going around the eye and the main leaf body. To overcome this problem, a second design was tried using transverse bandages of woven glass fibre reinforced tape to wrap the section that is prone to delaminate. In this case, the maximum interlaminar shear stress was reduced by a certain amount but it was still higher than the material’s shear strength. Based on the fact that, even with delamination, the top leaf spring still sustained the maximum static and fatigue loads required, the third design was proposed with an open eye-end, eliminating altogether the interface where the maximum shear stress occurs. The maximum shear stress predicted by FEA is reduced significantly and a safety factor of around 2 has been obtained. Thus, a successful and safe design has been achieved.

Effect of dietary phytate and microbial phytase on mineral and trace element bioavailability- a literature review

Phytic acid (PA) is the main phosphorus storage compound in cereals, legumes and oil seeds. In human populations where phytate-rich cereals such as wheat, maize and rice are a staple food, phytate may lead to mineral and trace element deficiency. Zinc appears to be the trace element whose bioavailability is most influenced by PA. Furthermore, several studies in humans as well as in monogastric animals clearly indicate an inhibition of non-haem iron absorption at marginal iron supply due to phytic acid. In fact PA seems to be, at least partly, responsible for the low absorption efficiency and high incidence of iron deficiency anaemia evident in most developing countries, where largely vegetarian diets are consumed Microbial phytases have provided a realistic means of improving mineral availability from traditionally high-phytate diets. In fact it has been consistently shown that Aspergillus phytases significantly enhance the absorption of calcium, magnesium and zinc in pigs and rats. Furthermore there are a few studies in humans indicating an improvement of iron bioavailability due to microbial phytase.

Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation

Dietary flavonoids, including the citrus flavanone hesperetin, may have stimulatory, effects on cytoprotective intracellular signalling pathways. In primary mouse cortical neurone cultures, but not SH-SY5Y human neuroblastoma cells or human primary dermal fibroblasts (Promocells), hesperetin (100-300 nM, 15 min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18 h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300 nM hesperetin partially reversed staurosporine-induced cell death in primary neurones. Our data show that hesperetin is a neuroprotective compound at concentrations where antioxidant effects are unlikely to predominate. The effects of hesperetin are cell-type dependent and, unlike the flavanol (-)epicatechin, neuroprotection in vitro is not associated with enhanced CREB phosphorylation or CRE-mediated gene expression. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Dietary flavonoid (-)epicatechin stimulates phosphatidylinositol 3-kinase-dependent anti-oxidant response element activity and up-regulates glutathione in cortical astrocytes

Flavonoids are plant-derived polyphenolic compounds with neuroprotective properties. Recent work suggests that, in addition to acting as hydrogen donors, they activate protective signalling pathways. The anti-oxidant response element (ARE) promotes the expression of protective proteins including those required for glutathione synthesis (xCT cystine antiporter, gamma-glutamylcysteine synthetase and glutathione synthase). The use of a luciferase reporter (ARE-luc) assay showed that the dietary flavan-3-ol (-)epicatechin activates this pathway in primary cortical astrocytes but not neurones. We also examined the distribution of NF-E2-related factor-2 (Nrf2), a key transcription factor in ARE-mediated gene expression. We found, using immunocytochemistry, that Nrf2 accumulated in the nuclei of astrocytes following exposure to tert-butylhydroquinone (100 mu M) and (-)epicatechin (100 nM). (-)Epicatechin signalling via Nrf2 was inhibited by wortmannin implicating a phosphatidylinositol 3-kinase-dependent pathway. Finally, (-)epicatechin increased glutathione levels in astrocytes consistent with an up-regulation of ARE-mediated gene expression. Together, this suggests that flavonoids may be cytoprotective by increasing anti-oxidant gene expression.

Asymmetric phase-transfer-catalyzed synthesis of five-membered cyclic gamma-Amino acid precursors

The first example of an intramolecular enantioselective Michael addition of nitronates onto conjugated systems utilizing a chiral phase-transfer catalyst is described. A range of five-membered gamma-nitro esters with up to three stereocentres have been prepared and the relative and absolute configurations proven by chemical and crystallographic methods. The products are rapidly obtained and are precursors to five-membered cyclic gamma-amino acids.

A β-amino acid modified heptapeptide containing a designed recognition element disrupts fibrillization of the amyloid β-peptide

We study the complex formation of a peptide betaAbetaAKLVFF, previously developed by our group, with Abeta(1–42) in aqueous solution. Circular dichroism spectroscopy is used to probe the interactions between betaAbetaAKLVFF and Abeta(1–42), and to study the secondary structure of the species in solution. Thioflavin T fluorescence spectroscopy shows that the population of fibers is higher in betaAbetaAKLVFF/Abeta(1–42) mixtures compared to pure Abeta(1–42) solutions. TEM and cryo-TEM demonstrate that co-incubation of betaAbetaAKLVFF with Abeta(1–42) causes the formation of extended dense networks of branched fibrils, very different from the straight fibrils observed for Abeta(1–42) alone. Neurotoxicity assays show that although betaAbetaAKLVFF alters the fibrillization of Abeta(1–42), it does not decrease the neurotoxicity, which suggests that toxic oligomeric Abeta(1–42) species are still present in the betaAbetaAKLVFF/Abeta(1–42) mixtures. Our results show that our designed peptide binds to Abeta(1–42) and changes the amyloid fibril morphology. This is shown to not necessarily translate into reduced toxicity.

Probing the effect of allylic substitution on cyclic ammonium ylid rearrangements

The [2,3]-sigmatropic rearrangement of tetrahydropyridine-derived ammonium ylids is a valuable method for the preparation of substituted pyrrolidine carboxylates. The presence of an allylic substituent does not intrinsically reduce the yield of rearrangements, and the diastereoselectivity of rearrangement is related to the structure of the diazo reactant. The method represents a very rapid means of accessing complex pyrrolidines, as shown by preparation of a precursor to the core of lactacystin.

Asymmetric synthesis of cyclic β-amino acids and cyclic amines via sequential diastereoselective conjugate addition and ring closing metathesis

Diastereoselective conjugate addition of lithium (S)-N-allyl-N-alpha-methylbenzylamide to a range of alpha,beta-unsaturated esters followed by ring closing metathesis is used to afford efficiently a range of substituted cyclic beta-amino esters in high d.e. Alternatively, conjugate addition to alpha,beta-unsaturated Weinreb amides, functional group conversion and ring closing metathesis affords cyclic amines in high d.e. The further application of this methodology to the synthesis of a range of carbocyclic beta-amino esters via conjugate addition, enolate alkylation and ring closing metathesis is also described. Application of this methodology affords, after deprotection, (S)-homoproline, (S)-homopipecolic acid, (S)-coniine and (1S,2S)-trans-pentacin.

An Exponentially Convergent Nonpolynomial Finite Element Method for Time-Harmonic Scattering from Polygons

In recent years nonpolynomial finite element methods have received increasing attention for the efficient solution of wave problems. As with their close cousin the method of particular solutions, high efficiency comes from using solutions to the Helmholtz equation as basis functions. We present and analyze such a method for the scattering of two-dimensional scalar waves from a polygonal domain that achieves exponential convergence purely by increasing the number of basis functions in each element. Key ingredients are the use of basis functions that capture the singularities at corners and the representation of the scattered field towards infinity by a combination of fundamental solutions. The solution is obtained by minimizing a least-squares functional, which we discretize in such a way that a matrix least-squares problem is obtained. We give computable exponential bounds on the rate of convergence of the least-squares functional that are in very good agreement with the observed numerical convergence. Challenging numerical examples, including a nonconvex polygon with several corner singularities, and a cavity domain, are solved to around 10 digits of accuracy with a few seconds of CPU time. The examples are implemented concisely with MPSpack, a MATLAB toolbox for wave computations with nonpolynomial basis functions, developed by the authors. A code example is included.