Convergence of products from Povarov and von Miller reactions: approaches to helquinoline

Yttrium triflate or triflic acid catalysed Povarov reaction of methyl anthranilate with ethyl vinyl ether, both as aldehyde surrogate and as alkene, gave the desired 2-methyl-4-ethoxytetrahydroquinoline diastereoisomers as the major products along with four component coupling von Miller adducts. A proton NMR-study, using yttrium triflate as catalyst, revealed that the cis-diastereoisomers were the initial major products in both the Povarov and von Miller reactions but that these isomerised to the trans-diastereoisomers under the reaction conditions. Two distinct pathways for forming von Miller adducts were uncovered with the initial Povarov products being converted to von Miller adducts under the reaction conditions. Replacement of the 4-ethoxy with a 4-methoxy group under acidic conditions gave predominantly the trans-diastereoisomer, which was subsequently converted to a cis/trans mixture of the tetrahydroquinoline antibiotic helquinoline. It was also possible to convert the von Miller products to Povarov products under acidic conditions

Aza-annulation of enaminones with itaconic anhydride:kinetic preference for exocyclic enamide products

Enaminones react with itaconic anhydride in methylene chloride at room temperature to give exocyclic enamides sis the major products. These can be readily equilibrated to the thermodynamically more stable endocyclic enamides. In substrates where the exocyclic isomer could not be formed only intractable materials were produced from this reaction. An intermediate in this two step process was detected and identified by proton and C-13 NMR spectroscopy. In two cases chiral enaminones were employed and the relative stereochemistry at the new chiral centre in the product was established by a crystal structure of compound 27.

A techno-economic evaluation of changing from conventional vehicles to range extended electric vehicles

Transportation accounts for 22% of greenhouse gas emissions in the UK, and increases to 25% in Northern Ireland. Surface transport carbon dioxide emissions, consisting of road and rail, are dominated by cars. Demand for mobility is rising rapidly and vehicle numbers are expected to more than double by 2050. Car manufacturers are working towards reducing their carbon footprint through improving fuel efficiency and controlling exhaust emissions. Fuel efficiency is now a key consideration of consumers purchasing a new vehicle. While measures have been taken to help to reduce pollutants, in the future, alternative technologies will have to be used in the transportation industry to achieve sustainability. There are currently many alternatives to the market leader, the internal combustion engine. These alternatives include hydrogen fuel cell vehicles and electric vehicles, a term which is widely used to cover battery electric vehicles, plug-in hybrid electric vehicles and extended-range electric vehicles. This study draws direct comparisons measuring the differing performance in terms of fuel consumption, carbon emissions and range of a typical family saloon car using different fuel types. These comparisons will then be analysed to see what effect switching from a conventionally fuelled vehicle to a range extended electric vehicle would have not only on the end user, but also the UK government.

Three motAB stator gene products in Bdellovibrio bacteriovorus contribute to motility of a single flagellum during predatory and prey-independent growth

The predatory bacterium Bdellovibrio bacteriovorus uses flagellar motility to locate regions rich in Gram-negative prey bacteria, colliding and attaching to prey and then ceasing flagellar motility. Prey are then invaded to form a "bdelloplast" in a type IV pilus-dependent process, and prey contents are digested, allowing Bdellovibrio growth and septation. After septation, Bdellovibrio flagellar motility resumes inside the prey bdelloplast prior to its lysis and escape of Bdellovibrio progeny. Bdellovibrio can also grow slowly outside prey as long flagellate host-independent (HI) cells, cultured on peptone-rich media. The B. bacteriovorus HD100 genome encodes three pairs of MotAB flagellar motor proteins, each of which could potentially form an inner membrane ion channel, interact with the FliG flagellar rotor ring, and produce flagellar rotation. In 2004, Flannagan and coworkers (R. S. Flannagan, M. A. Valvano, and S. F. Koval, Microbiology 150:649-656, 2004) used antisense RNA and green fluorescent protein (GFP) expression to downregulate a single Bdellovibrio motA gene and reported slowed release from the bdelloplast and altered motility of the progeny. Here we inactivated each pair of motAB genes and found that each pair contributes to motility, both predatorily, inside the bdelloplast and during HI growth; however, each pair was dispensable, and deletion of no pair abolished motility totally. Driving-ion studies with phenamil, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and different pH and sodium conditions indicated that all Mot pairs are proton driven, although the sequence similarities of each Mot pair suggests that some may originate from halophilic species. Thus, Bdellovibrio is a "dedicated motorist," retaining and expressing three pairs of mot genes.

On the halogenation of N(1),N(2)-di-t-Boc-5-hydroxy-piperazic acid esters and the conformational preferences of their 5-halo-piperazic acid products. The importance of A1,3 rotameric-strain in determining N(2)-acyl piperazic acid ring conformation

In this Letter, an unambiguous synthetic strategy is reported for the preparation of enantiomerically purecis-5-halo-piperazic acid derivatives in single diastereoisomer form. Contrary to the recent report by Shin and co-workers (Chem. Lett. 2001, 1172), in which it is claimed that the Ph₃P and N-chlorosuccinimide (NCS)-mediated chlorination of (3R,5S)-trans-N(1),N(2)-di-t-Boc-5-hydroxy-piperazic acid derivative 1proceeds with retention of configuration at C(5) to give 2, we now show that this and related Ph₃P-mediated halogenations all occur with S_N2 inversion at the alcohol center, as is customary for such reactions. Specifically, we demonstrate that the (3R,5S)-trans-5-Cl-piperazic acid derivative 2 claimed by Shin and co-workers (Chem. Lett. 2001, 1172) is in actual fact the chlorinated (3S,5R)-enantiomer 6, which must have been prepared from the cis-(3S,5S)-alcohol 3, a molecule whose synthesis is not formally described in the Shin paper. We further show here that the cis-(3R,5R)-5-Cl-Piz 13 claimed by Shin and co-workers inChem. Lett. 2001, 1172, is also (3S,5R)-trans-5-Cl-Piz 6. Authentic 13 has now been synthesized by us, for the very first time, here. Since Lindsley and Kennedy have recently utilized the now invalid Shin and co-workers’ retentive Ph₃P/NCS chlorination procedure on 1 in their synthetic approach to piperazimycin A (Tetrahedron Lett. 2010, 51, 2493), it follows that their claimed 5-Cl-Piz-containing dipeptide 25 probably has the alternate structure 26, where the 5-Cl-Piz residue has a 3,5-cis-configuration. The aforementioned stereochemical misassignments appear to have come from a mix-up of starting materials by Shin and co-workers (Chem. Lett. 2001, 1172), and an under-appreciation of the various steric and conformational effects that operate in N(2)-acylated piperazic acid systems, most especially rotameric A^1,3-strain. The latter has now been unambiguously delineated and defined here under the banner of the A^1,3-rotamer effect.

Efficacy of instant hand sanitizers against foodborne pathogens compared to hand washing with soap and water in food preparation settings: a systematic review

Hands can be a vector for transmitting pathogenic microorganisms to foodstuffs and drinks, and to the mouths of susceptible hosts. Hand washing is the primary barrier to prevent transmission of enteric pathogens via cross contamination from infected persons. Conventional hand washing involves the use of warm water, soap and friction to remove dirt and microorganisms. Over recent years there has been an increasing availability of hand sanitizing products for use when water and soap are unavailable. The aim of this systematic review was to collate scientific information on the efficacy of hand sanitizers compared to hand washing with soap and water for the removal of foodborne pathogens from the hands of food handlers. An extensive literature search was carried out using three electronic databases - Web of Science, Scopus and PubMed. Twenty-eight scientific publications were ultimately included in the review. Analysis of the literature showed various limitations in the scientific information due to the absence of a standardized protocol to evaluate efficacy of hand products, and variation in experimental conditions applied in different studies. Despite the existence of conflicting results, scientific evidence seems to support the historical scepticism about the use of water-less hand sanitizers in food preparation settings. Water and soap appear to achieve greater removal of soil and microorganisms than water-less products from hands. None of the hand sanitizers tested in the literature seemed to achieve complete inactivation or removal of all foodborne pathogens tested, and the presence of food debris significantly affected inactivation rates of hand products.

Patient safety and beyond: what should we expect from microneedle arrays in the transdermal delivery arena?

Research based upon microneedle (MN) arrays has intensified recently. While the initial focus was on biomolecules, the field has expanded to include delivery of conventional small-molecule drugs whose water solubility currently precludes transdermal administration. Much success has been achieved, with peptides, proteins, vaccines, antibodies and even particulates delivered by MN in therapeutic/prophylactic doses. Recent innovations have focused on enhanced formulation design, scalable manufacture and extension of exploitation to minimally invasive patient monitoring, ocular delivery and enhanced administration of cosmeceuticals. Only two MN-based drug/vaccine delivery products are currently marketed, partially due to limitations with older MN designs based upon silicon and metal. Even the more promising polymeric MN have raised a number of regulatory and manufacturability queries that the field must address. MN arrays have tremendous potential to yield real benefits for patients and industry and, through diligence, innovation and collaboration, this will begin to be realised over the next 3-5 years.

Increasing Fruit and Vegetable Intake Has No Dose-Response Effect on Conventional Cardiovascular Risk Factors in Overweight Adults at High Risk of Developing Cardiovascular Disease

BACKGROUND: Improving diet and lifestyle is important for prevention of cardiovascular disease (CVD). Observational evidence suggests that increasing fruit and vegetable (FV) consumption may lower CVD risk, largely through modulation of established risk factors, but intervention data are required to fully elucidate the mechanisms by which FVs exert benefits on vascular health.

OBJECTIVE: The aim of this study was to examine the dose-response effect of FV intake on cardiovascular risk factors in adults at high CVD risk.

METHODS: This was a randomized controlled parallel group study involving overweight adults (BMI: >27 and ≤35 kg/m(2)) with a habitually low FV intake (≤160 g/d) and a high total risk of developing CVD (estimated ≥20% over 10 y). After a 4-wk run-in period where FV intake was limited to <2 portions/d (<160 g/d), 92 eligible participants were randomly assigned to 1 of 3 groups: to consume either 2, 4, or 7 portions (equivalent to 160 g, 320 g, or 560 g, respectively) of FVs daily for 12 consecutive weeks. Fasting venous blood samples were collected at baseline (week 4) and post-intervention (week 16) for analysis of lipid fractions and high-sensitivity C-reactive protein (hsCRP) concentrations. Compliance with the FV intervention was determined with use of self-reported FV intake and biomarkers of micronutrient status. Ambulatory blood pressure and body composition were also measured pre- and post-intervention.

RESULTS: A total of 89 participants completed the study and body composition remained stable throughout the intervention period. Despite good compliance with the intervention, no significant difference was found between the FV groups for change in measures of ambulatory blood pressure, plasma lipids, or hsCRP concentrations.

CONCLUSIONS: There was no evidence of a dose-response effect of FV intake on conventional CVD risk factors measured in overweight adults at high CVD risk. This trial was registered at clinicaltrials.gov as NCT00874341.

In Situ Gelling Ophthalmic Drug Delivery System: An Overview and Its Applications.

Ophthalmic drug delivery system is very interesting and challenging due to the normal physiologically factor of eyes which reduces the bioavailability of ocular products. The development of a new ophthalmic dosage forms with the existing drugs to improve efficacy and bioavailability including better patients' compliance and convenience has become trend in the most pharmaceutical industries. The present review encompasses various conventional and novel ocular drug delivery systems, methods of preparation, characterization, recent researches carried out. Furthermore, the information on various commercially available in situ gel preparations and the existing patents of in situ drug delivery systems i.e. in situ gel formation of pectin, in situ gel for therapeutic use, medical uses of in situ formed gels and in situ gelling systems as sustained delivery for front of eye also covered in this review.

PESSTO: Survey description and products from the first data release by the Public ESO Spectroscopic Survey of Transient Objects

Context. The Public European Southern Observatory Spectroscopic Survey of Transient Objects (PESSTO) began as a public spectroscopic survey in April 2012. PESSTO classifies transients from publicly available sources and wide-field surveys, and selects science targets for detailed spectroscopic and photometric follow-up. PESSTO runs for nine months of the year, January - April and August - December inclusive, and typically has allocations of 10 nights per month. 

Aims. We describe the data reduction strategy and data products that are publicly available through the ESO archive as the Spectroscopic Survey data release 1 (SSDR1). 

Methods. PESSTO uses the New Technology Telescope with the instruments EFOSC2 and SOFI to provide optical and NIR spectroscopy and imaging. We target supernovae and optical transients brighter than 20.5^m for classification. Science targets are selected for follow-up based on the PESSTO science goal of extending knowledge of the extremes of the supernova population. We use standard EFOSC2 set-ups providing spectra with resolutions of 13-18 Å between 3345-9995 Å. A subset of the brighter science targets are selected for SOFI spectroscopy with the blue and red grisms (0.935-2.53 μm and resolutions 23-33 Å) and imaging with broadband JHK<inf>s</inf> filters. 

Results. This first data release (SSDR1) contains flux calibrated spectra from the first year (April 2012-2013). A total of 221 confirmed supernovae were classified, and we released calibrated optical spectra and classifications publicly within 24 h of the data being taken (via WISeREP). The data in SSDR1 replace those released spectra. They have more reliable and quantifiable flux calibrations, correction for telluric absorption, and are made available in standard ESO Phase 3 formats. We estimate the absolute accuracy of the flux calibrations for EFOSC2 across the whole survey in SSDR1 to be typically ∼15%, although a number of spectra will have less reliable absolute flux calibration because of weather and slit losses. Acquisition images for each spectrum are available which, in principle, can allow the user to refine the absolute flux calibration. The standard NIR reduction process does not produce high accuracy absolute spectrophotometry but synthetic photometry with accompanying JHK<inf>s</inf> imaging can improve this. Whenever possible, reduced SOFI images are provided to allow this. 

Conclusions. Future data releases will focus on improving the automated flux calibration of the data products. The rapid turnaround between discovery and classification and access to reliable pipeline processed data products has allowed early science papers in the first few months of the survey.

Process for the preparation of water-soluble cellulose hydrolysis products.

The title process comprises admixing cellulose with an ionic liq. capable of solvating or dissolving at least some of the cellulose, the ionic liq. being a compd. comprised solely of cations and anions (e.g., 1-ethyl-3-methylimidazolium sulfate) and which exists in a liq. state at a temp. at or below 150°, and in which the anions are selected from sulfate, hydrogen sulfate and nitrate; and treating the resulting solvate or soln. with an acid in the presence of water, the acid having a pKa in water of less than 2 at 25°. [on SciFinder(R)]