Search

A comparative study has been made of the performance of differently substituted Ca-symmetric bis(aziridine) ligands in a variety of metal-mediated asymmetric reactions. The metals studied were osmi ...

During 1996, the Chester & Halton Community NHSTrust in the UK undertook a project to explore the means of contracting for cancer services in the community, which embraced a care profiles approach. In the project, care profiles were developed for community nurses and community palliative care nurses. It was considered that such focused, uni-professional care profiles would be applied using a ‘building block’ approach.The view was taken that cancer services in the community were essentially generic in nature, and no distinction needed to be made between different cancer sites. The focus of this paper is the process used to develop care profiles for patients suffering from malignant disease who are being nursed in the community. Care profiles are based on identified care aims, which include the assessment of need, the maintenance of an existing level of comfort in terminal illness, and palliative and bereavement care. The definitions of care aims were those developed in a national community minimum datasets project. At the close of the project, it was concluded by the clinicians involved that care profiles are both practical and straightforward to develop, and represent a valid and valuable means of commissioning services.

The chiral aziridino alcohols 1 -3 have been prepared either from amino acids (1a from serine; 1b - 1i and 3 from threonine; 2a - 2e from allo-threonine) or via asymmetric synthesis (1j, 1k, 1l and ...

Enantioselective Addition of Organolithium Reagents to Imines Mediated by C2-Symmetric Bis(aziridine) Ligands

A convergent enantioselective total synthesis of the neurotoxic spirocyclic alkaloid (−)-perhydrohistrionicotoxin (2) is described. A Lewis acid-mediated intramolecular imine ene-type reaction was used for the key spirocyclisation step (14 to 3, with 3 being obtained as a single diastereoisomer). Spirocyclisation precursor 14 was prepared from enantiomerically pure ketone 13, itself available via an efficient one-pot, three-component, coupling reaction involving chiral electrophiles 9 and 10. The stereogenic centres of 9 and 10 derive in turn from Sharpless kinetic resolution, which allowed access to both chiral electrophiles from a common racemic precursor, 8.

A high yielding solid-phase dimerisation of 2-naphthol by means of a ball-milling procedure is described. Present address: Nycomed Innovation AB, Ideon Malm⊘, S-20512, Malm⊘, Sweden.

The regioselectivity of nucleophilic ring opening of some 3,4-epoxy and 3,4-aziridino alcohols has been studied. The nucleophiles chosen were complex hydrides (LiAlH4, Red-Al and DIBAL) and Lipshutz- or Gilman-type organocuprate reagents. The C-4 substituent in the substrates was varied in order to study steric and electronic effects on the ring opening reactions. For alkyl substituents at C-4, most of the results can be explained on the basis of intramolecular delivery of the nucleophile to C-3 via a six-membered transition state, leading to 1,4-diols or 1,4-amino alcohol derivatives. In general, the epoxy alcohols gave poorer regioselectivity than the N-tosyl aziridino alcohols, for which selectivities of >95:5 were routinely obtained. The activating effect of a phenyl group at C-4 led to a switch in regiochemistry, with the 1,3-diol or 1,3-amino alcohol derivative as the major product.

A convergent enantioselective total synthesis of the natural product (-)-balanol (1) is described. In addition to benzophenone fragment 8, key intermediates are chiral bicyclic aziridine 3 and the corresponding epoxide 4, both of which undergo highly regio- and stereoselective nucleophilic ring-opening reactions, allowing control of the two stereogenic centres of the target molecule. The structure and reactivity of 3 and 4 have been investigated in some detail.

This paper describes the construction of three key intermediates 11, 15 and 23 for a projected total synthesis of the marine alkaloid zoanthamine. These building blocks, corresponding to the C-1-C-5, C-6-C-10, and C-11-C-24 fragments of the target molecu

In contrast to a recent report, continuum models give a fair description of the solvation of chloride and other small anions.

The chiral bis(aziridines) 4, 6 and 7 have been synthesized and evaluated as chelating ligands for a variety of asymmetric transformations mediated by metals. The processes studied were the asymmetric addition of osmium tetroxide to olefins, copper-catal

A study has been made of the regio-and Stereoselectivity of the ring opening reactions of the 3-aryl substituted aziridines 1 and 2. The regiochemical outcome is apparently decided by a balance of electronic activation at C-3 by the phenyl group and the chelating effects of C-1 oxygen functionality which can direct nucleophiles intramoleculary to C-2 or C-3. Good levels of regiocontrol for either C-3 or C-2 attack are obtained particularly for the reactions of aziridino alcohols 1a and 2a with hydride reagents, while methyl-transfer reagents such as LiMe 2 Cu and AlMe 3 tend to give exclusive C-3 attack with inversion (cuprate) or inversion plus retention (trialkylaluminum). Possible reaction mechanisms (inter-vs. intramolecular) are discussed.

Three different routes to the hexahydroazepine unit of the natural products balanol ( 1 ) and ophiocordin ( 2 ) are described. The common starting material is the chiral epoxy alcohol 3 which is converted to the balanol degradation product 10 (Scheme 1) or to suitably protected derivatives thereof: 15 (Scheme 2) and 19 (Scheme 3). A key step in the first route is the acid-catalysed ring-opening of bicyclic aziridine 8 which proceeds in good chemical yield (71% isolated) and with remarkable regioselectivity (98:2 in favour of the desired regioisomer).

Studies of Allylic Substitution Catalysed by a Palladium Complex of a C2-Symmetric Bis(aziridine): Preparation and NMR Spectroscopic Investigation of a Chiral n-Allyl Species

Particle physics aims to understand the universe around us. The Standard Model of particle physics describes the basic structure of matter and forces, to the extent we have been able to probe thus far. However, it leaves some big questions unanswered. Some are within the Standard Model itself, such as why there are so many fundamental particles and why they have different masses. In other cases, the Standard Model simply fails to explain some phenomena, such as the observed matter-antimatter asymmetry in the universe, the existence of dark matter and dark energy, and the mechanism that reconciles gravity with quantum mechanics. These gaps lead us to conclude that the universe must contain new and unexplored elements of Nature. Most of particle and nuclear physics is directed towards discovering and understanding these new laws of physics. These questions are best pursued with a variety of approaches, rather than with a single experiment or technique. Particle physics uses three basic approaches, often characterized as exploration along the cosmic, energy, and intensity frontiers. Each employs different tools and techniques, but they ultimately address the same fundamental questions. This allows a multi-pronged approach where attacking basic questions from different angles furthers knowledge and providesmore » deeper answers, so that the whole is more than a sum of the parts. A coherent picture or underlying theoretical model can more easily emerge, to be proven correct or not. The intensity frontier explores fundamental physics with intense sources and ultra-sensitive, sometimes massive detectors. It encompasses searches for extremely rare processes and for tiny deviations from Standard Model expectations. Intensity frontier experiments use precision measurements to probe quantum effects. They typically investigate very large energy scales, even higher than the kinematic reach of high energy particle accelerators. The science addresses basic questions, such as: Are there new sources of CP violation? Is there CP violation in the leptonic sector? Are neutrinos their own antiparticles? Do the forces unify? Is there a weakly coupled hidden sector that is related to dark matter? Do new symmetries exist at very high energy scales? To identify the most compelling science opportunities in this area, the workshop Fundamental Physics at the Intensity Frontier was held in December 2011, sponsored by the Office of High Energy Physics in the US Department of Energy Office of Science. Participants investigated the most promising experiments to exploit these opportunities and described the knowledge that can be gained from such a program. The workshop generated much interest in the community, as witnessed by the large and energetic participation by a broad spectrum of scientists. This document chronicles the activities of the workshop, with contributions by more than 450 authors. The workshop organized the intensity frontier science program along six topics that formed the basis for working groups: experiments that probe (i) heavy quarks, (ii) charged leptons, (iii) neutrinos, (iv) proton decay, (v) light, weakly interacting particles, and (vi) nucleons, nuclei, and atoms. The conveners for each working group included an experimenter and a theorist working in the field and an observer from the community at large. The working groups began their efforts well in advance of the workshop, holding regular meetings and soliciting written contributions. Specific avenues of exploration were identified by each working group. Experiments that study rare strange, charm, and bottom meson decays provide a broad program of measurements that are sensitive to new interactions. Charged leptons, particularly muons and taus, provide a precise probe for new physics because the Standard Model predictions for their properties are very accurate. Research at the intensity frontier can reveal CP violation in the lepton sector, and elucidate whether neutrinos are their own antiparticles. A very weakly coupled hidden-sector that may comprise the dark matter in the universe could be discovered. The search for proton decay can probe the unification of the forces with unprecedented reach and test sacrosanct symmetries to very high scales. Detecting an electric dipole moment for the neutron, or neutral atoms, could establish a clear signal for new physics, while limits on such a measurement would place severe constraints on many new theories. This workshop marked the first instance where discussion of these diverse programs was held under one roof. As a result, it was realized that this broad effort has many connections; a large degree of synergy exists between the different areas and they address similar questions. Results from one area were found to be pertinent to experiments in another domain.« less

An integration process was developed for the fabrication of rear passivated point contact solar cells achieving 19.36% conversion efficiency by using 156×156mm, pseudo square, p-type single crystalline silicon wafers. This is a significant improvement when compared to unpassivated, full area aluminum back surface field solar cells, which exhibit only 18.64% conversion efficiency on the same wafer type. The rear surface was passivated with a Al 2 O 3 layer and a SiN X capping layer. The thicknesses of individual films were optimized to obtain maximum minority carrier lifetimes. The rear surface contact pattern was created by laser ablation and the contact geometry was optimized to obtain voids free contact filling resulting in a uniform back surface field. Internal quantum efficiency and reflectance measurement show significant improvement in rear passivated cells in the infrared wavelength region in comparison to reference cells. The rear surface internal reflectivity for the passivated cell was 93% while that for the reference cell was only about 73%. The rear surface recombination velocity for the rear passivated cell was about 52 cm/s while that for the reference cell was about 300 cm/s. The efficiency gain in rear passivated cells over the reference cells is mainly due to improved short circuit current and open circuit voltage. However, rear passivated solar cells show lower fill factors due to increased series resistance.

This work reports on the integration process of rear point contact solar cells with reduced recombination and better light trapping than the conventional cells. Al 2 O 3 /SiN x passivation stacks were used to ensure the backside passivation and the effective lifetime of minority carrier is found to be >100 µs (estimated surface recombination velocity ∼50 cm/s) on solar p-type Cz wafers. The estimated fixed charge associated with the Al 2 O 3 is in the range of −5e12 C/cm2. Laser ablation of Al 2 O 3 /SiN x stack and aluminum alloying are studied in detail to understand the process window for clean ablation and back surface field. It is found that laser energy plays an important role cleanly ablating the Al 2 O 3 /SiN x passivation stack. The solar cell is fabricated using standard processes based on screen-printed aluminum paste onto laser ablated passivation layer consisting of Al 2 O 3 /SiN x . Aluminum alloying is dependent on the firing profile and amount of Al melted into Si. Back point contact cells show improvements in J sc by 1 mA/cm2 and V oc by 10 mV due to better response in infrared spectrum. The best conversion efficiency of back point contact solar cells fabricated with standard industrial emitter and backside passivation is 19.35%.

The readily available C2-symmetric bis(aziridines) 1 can act as ligands in a variety of asymmetric transformations mediated by transition metals. In the best cases, >95% ee can be obtained.

The preparation of enantiomerically pure compounds is one of the major areas of organic chemistry. Much emphasis is placed on the elaboration of naturally occurring starting materials and on the development of techniques for enantio-selective transformations of achiral substrates. In this field, chiral aziridines form an attractive class of compounds, since they are available in enantiomerically pure (or highly enriched) form by a variety of procedures and can be used for asymmetric synthesis in a number of different ways. The chemistry of aziridines is dominated by ring-opening reactions, the driving force for which is relief of ring strain. By suitable choice of sub-stituents on the carbon and nitrogen atoms, excellent stereo- and regiocontrol can be attained in ring-opening reactions with a wide variety of nucleophiles, including organometallic reagents; this makes chiral aziridines useful as substrates for the synthesis of important biologically active species including alkaloids, amino acids, and /Mactam antibiotics. Substrate-controlled diastereo-selective synthesis is also possible by use of aziridines as removable chiral auxiliaries, while metalation at a ring carbon atom allows aziridines to be used as chiral reagents for asymmetric synthesis. Chiral bisaziridines can act as ligands for transition metals, and applications in the challenging field of enantioselective catalysis can be envisioned. Today, the exclusion of three-membered carbo- and heterocycles from the arsenal of the organic chemist is inconceivable.

Die Herstellung enantiomerenreiner Verbindungen nimmt innerhalb der Organischen Chemie einen weiten Raum ein. Besonderes Augenmerk liegt dabei auf der Nutzung naturlich vorkommender Ausgangsmaterialien und auf der Entwicklung von Methoden zur enantioselektiven Umsetzung achiraler Substrate. Chirale Aziridine sind in diesem Zusammenhang eine attraktive Verbindungsklasse, da sie uber eine Vielzahl von Verfahren enantiomerenrein oder in hohen Enantiomerenuberschussen verfugbar sind und zudem auf verschiedenste Weise in der asymmetrischen Synthese genutzt werden konnen. Die Chemie der Aziridine wird durch ringoffnende Reaktionen bestimmt, deren Triebkraft in der Aufhebung von Ringspannung liegt. Durch geeignete Wahl der Substituenten an Stickstoff- und Kohlenstoffatomen gelingt es, in ringoffnenden Reaktionen mit unterschiedlichsten Nucleophilen einschlieslich metallorganischen Verbindungen exzellente Stereo- und Regiokontrolle zu erzielen. Dadurch werden chirale Aziridine zu wertvollen Substraten fur die Synthese wichtiger biologisch aktiver Vebindungen, z.B. Alkaloiden, Aminosauren und β-Lactam-Antibiotika, Diastereoselektive Synthesen unter Substratkontrolle sind moglich, wenn Aziridine als abspaltbare chirale Auxiliare eingesetzt werden. Nach Metallierung am Ringkohlenstoffatom konnen Aziridine auch als chirale Reagentien in der asymmetrischen Synthese benutzt werden. Da chirale Bisaziridine auch als Liganden fur Ubergangsmetalle wirken konnen, rukken Anwendungen in dem herausfordernden Gebiet der enantioselektiven Katalyse ins Blickfeld. Der Ausschlus dreigliedriger Carbo-und Heterocyclen aus dem Werkzeugkasten des organischen Chemikers erscheint heutzutage unvorstellbar[1].

A systematic study has been made of the utility of readily available C 2 -symmetric aziridines as auxiliaries for asymmetric alkylation and aldol rea

A synthetic approach to the marine alkaloid Zoanthamine is outlined. Starting with (-)- perilly alkohol, the C-11 to C-20 fragment 9b has been synthesized in 12 operations and > 30% overall yield. Model studies for a proposed intramolecular Diels-Alder strategy are also described.

A novel optical metrology technique has been developed to study textured silicon wafers used to manufacture solar cells. This high efficiency optical design to maximize the signal from surfaces with reflectivity well below 1% was developed. Pyramid dimensions were measured on as sawed p-type Czochralski wafers having a bulk resistivity of 1–5 Ohm-cm. These wafers were subjected to a single step texturization process by using a non-alcoholic chemical etching formulation. Results were compared with SEM imaging. Reflectivity tests and pyramid height measurements were used to study the efficiency of the texturing processes. In a related study [2] it was found that 20μm of material removal was required to attain minimum surface reflectivity. Further removal of material affected pyramid dimensions, but did not improve surface reflectivity.

Optical analysis is performed for mono-crystalline silicon wafers with and without the texture and with and without the POCl doping, the passivating anti-reflective nitride film on front surface, and the screen printed aluminum conductor on the back surface. Reflectance is measured in the wavelength range from 300 nm to 1200 nm. Modeling of the light reflectance, absorbance, and transmittance is done using ray-tracing technique for the regular and the random texture patterns. Good agreement of measured and modeled data is obtained for the sub — 1 micron wavelengths by using standard material optical properties. However, the infrared light above the 1 micron wavelength requires accounting for several mono-layers thick native oxide present on silicon surfaces and adjusting the optical properties of specific nitride and aluminum films used in the solar cell manufacturing. It is found that the random texture exhibits 15% to 20% better light capture than the regular texture. Theoretical analysis provides plausible explanation of this effect and suggests a way to further improve optical performance of the textured surfaces. The optical modeling methodology can be used to find the optimum combination of texture and passivating/contact films for different solar cell designs.

Sawed p-type Czochralski wafers with a bulk resistivity of 1–5ωcm were subjected to single step texturization process by using a non-alcoholic chemical etching formulation. The minimum amount of silicon removal required for achieving optimum solar cell efficiencies was estimated by measuring cell efficiency as a function of silicon loss. The surface damage layer of as cut wafers was found to be approximately 6μm deep as indicated by the minority carrier lifetime measurements. However for attaining minimum surface reflectivity it was required to remove at least 20μm of silicon from the initial wafer. Further removal of silicon offered no additional improvements in surface reflectivity or the solar cell efficiency.

When valuable delicate goods are shipped by truck, attention must be paid to vibrations that may cause damage. We present a case study of moving an extremely delicate 6230-kg superconducting magnet, immersed in liquid nitrogen, from Livermore, CA to Seattle, WA showing the steps of fatigue analysis of the load, a test move, and acceleration monitoring of the final move to ensure a successful damage-free transport. The ADMX collaboration gratefully acknowledges support by the state of Washington under budget number 74-0474 SULRMV and the U.S. Department of Energy and Office of High Energy Physics under contract numbers DE-AC52- 07NA27344 (Lawrence Livermore National Laboratory), and DE-FG02-97ER41029 (University of Florida). Additional support was provided by Lawrence Livermore National Laboratory under the LDRD program. This research was supported by the Director, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division, of the U.S. Department of Energy under Contract No. DE-AC03- 76SF00098 (JC). The ADMX collaboration gratefully acknowledges support by the state of Washington under budget number 74-0474 SULRMV and the U.S. Department of Energy and Office of High Energy Physics under contract numbers DE-AC52- 07NA27344 (Lawrence Livermore National Laboratory), and DE-FG02-97ER41029 (University of Florida). Additional support was provided by Lawrence Livermore National Laboratory under the LDRD program. This research was supported by the Director, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division, of the U.S. Department of Energy under Contract No. DE-AC03- 76SF00098 (JC).

Herein is described the synthesis of a novel class of peptidyl FVIIa inhibitors having a C-terminal benzyl ketone group. This class is designed to be potentially suitable as stabilization agents of liquid formulations of rFVIIa, which is a serine protease used for the treatment of hemophilia A and B inhibitor patients. A library of compounds was synthesized with different tripeptide sequences, N-terminals and d -amino acids in the P3 position. Cbz- d -Phe–Phe–Arg–bk (33) was found to be the best candidate with a potency of Ki = 8 μM and no substantial inhibition of related blood coagulation factors (thrombin and FXa). Computational studies revealed that 33 has a very stable binding conformation due to intramolecular hydrogen bonds, which cannot be formed with l -Phe in the P3 position. Nonpolar amino acids were found to be superior, probably due to a minimization of the cost of desolvation upon binding to FVIIa.

The regio- and stereoselective carbonylation of optically pure trans vinylaziridine 5 to trans 3-vinylazetidinone 6 is catalyzed by Pd(0). Compound 6 is then transformed to a known key intermediate for the total synthesis of the carbapenem antibiotic (+)-PS-5.

The non-racemic C2-symmetric azirdines7 and8, easily available from (+)- and (-)-tartaric acid, respectively, undergo rapid nucleophilic attack to yield products formally derived from the β-cation ofL- orD-aspartic acid.

The C2-symmetric aziridines 1 and 1′ (available from (+)- and (−)-tartaric acid, respectively) are excellent chiral auxiliaries for asymmetric alkylation and aldol reactions.

A novel and diastereoselective entry to the β-lactam nucleus of the carbapenems starting from L-glutamic acid is exemplified by the synthesis of the potential (+)-PS-5 intermediate 13 .

Nucleophilic ring-opening of trans and cis aziridino alcohols 1 ( 1′ ) and 2 ( 2′ ) by hydride- and by methyl-transfer reagents has been studied. In general, good to excellent C-2 selectivity was observed (the regioselectivity being better for the trans isomers) and the results can be interpreted in terms of directive effects exerted by the C-1 hydroxyl group. However, complete C-3 selectivity was observed in the reactions of 1 and 2 with AlMe 3 , indicating a complexation effect of the C-4 benzyloxy group in those cases.