The chemistry of ynol and thioynol ethers

Alkynyl ethers and alkynyl thioethers (‘ynol ethers’ and ‘thioynol ethers’) are appealing building-blocks in synthetic chemistry due to their ease of manipulation and predictable reactivity. Until recently however, their potential has remained underexploited due to difficulties in preparation and isolation. Although recent advances in synthetic chemistry have highlighted various applications for ynol ethers, the equivalent thioynol examples have been rather less exploited despite a unique and fascinating reactivity profile. Although superficially the chemistry of alkynyl ethers and their sulfide counterparts are similar, close examination of their chemistry reveals important differences which can be exploited by the synthetic chemist. This review will examine the preparation of both classes of compound and examine their reactivity to highlight their powerful synthetic applications. Particular focus will be made of thiynol ethers whose chemistry exhibits some fascinating differences compared to their oxygen counterparts and have immense untapped potential for synthetic chemistry

New Applications for Sulfur-Based Leaving Groups in Synthesis

This thesis describes the discovery and development of new routes towards substituted indoles and ynol ethers based on a sulfonate and sulfonamide leaving group, respectively. Both syntheses involve the use of these electron-withdrawing moieties as α-radical stabilising groups that can be utilised in a range of mild and facile bond-forming reactions to yield useful organic compounds. The first approach describes the synthesis of indoles utilising a water soluble, phosphorus-based chain carrier that generates a carbon-centred radical from an sp3 bromo sulfonate ester. This species can consequently undergo an intramolecular cyclisation with an aromatic ring, followed by loss of the sulfonate ester to yield a range of indoles in a chemoselective fashion. The second part of this thesis describes the synthesis of a range of ynol ethers via reaction of an aliphatic potassium alkoxide with an aromatic alkynyl sulfonamide. The mechanism of this process has been explored via a combination of synthetic chemistry and electron paramagnetic resonance spectroscopy (EPR) and the findings of these experiments will be discussed. The synthesis of tert-butyl ynol ethers in particular, allows for retro-ene decomposition to yield a ketene. This reactive intermediate can consequently undergo [2+2] cycloaddition with a ynol ether to yield tri-substituted cyclobutenones in excellent yield. Based on these findings, a new mode of reactivity for potassium alkoxides is suggested that involves these compounds ionising at room temperature under certain conditions to form either stabilised alkoxyl or trioxyl radical complexes that are observable via EPR, where the latter complex is known to decompose to alkoxyl radicals and molecular oxygen. The work presented in this thesis may have implications for other areas of science such as atmospheric chemistry and transition-metal free cross-coupling chemistry

Transition-metal-free synthesis of ynol ethers and thioynol ethers via displacement at sp centers: a revised mechanistic pathway

We present here valuable extensions to our previous work in preparing highly functionalized, heteroatom-substituted alkynes via displacement at an sp center. Our results show that a wide range of ynol ethers can be prepared by the same methodology and that the same protocol can be applied to the synthesis of synthetically useful thioynol ethers. We also present new observations that have led us to revise our original hypothesis in favor of a pathway involving radical intermediates

Observations on transition metal free biaryl coupling: potassium tert-butoxide alone promotes the reaction without diamine or phenanthroline catalysts

Biaryl coupling (often labelled 'C-H activation') of aromatic systems can be achieved by potassium tert-butoxide alone in the absence of any amine or bipyridine catalyst (1,10-phenanthroline or N,N'-dimethylethylenediamine being the most common), previously reported to be essential. Various mechanistic studies and observations are presented which suggest that when 1,10-phenanthroline is employed as the catalyst, the alkoxide is destroyed almost immediately

Metal-macrofauna interactions determine microbial community structure and function in copper contaminated sediments

Peer reviewedPublisher PD

Vertical distribution of fish larvae in the Canaries-African coastal transition zone, in summer

13 pages, 6 figures, 2 tables.-- Printed version published Jul 2006.This study reports the vertical distribution of fish larvae during the 1999 summer upwelling season in the Canaries-African Coastal Transition Zone (the Canaries-ACTZ). The transition between the African coastal upwelling and the typical subtropical offshore conditions is a region of intense mesoscale activity that supports a larval fish population dominated by African neritic species. During the study, the thermal stratification extended almost to the surface everywhere, and the surface mixed layer was typically shallow or non-existent. Upwelling occurred on the African shelf in a limited coastal sub-area of our sampling. The vertical distributions of the entire larval fish population, as well as of individual species, were independent of the seasonal thermocline. Fish larvae and mesozooplankton were concentrated at intermediate depths regardless of the thermocline position, probably because of its weak signature and spatial and temporal variability. Day/night vertical distributions suggest that some species did not perform diel vertical migration (DVM), whereas others showed either type I DVM or type II DVM. The opposing DVM patterns of different species compensate for each other resulting in no net DVM for the larval fish population as a whole.Fieldwork was carried out as part of the CANIGO project, funded by the EU, and of the "Pelagic (EU-CICYT 1FD97-1084)" project from the Spanish Ministry of Education and the European Union

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes

Health-related Quality of Life among hospitalized older people awaiting residential aged care

BACKGROUND: Health related quality of life (HRQoL) in very late life is not well understood. The aim of the present study was to assess HRQoL and health outcomes at four months follow-up in a group of older people awaiting transfer to residential aged care. METHODS: Secondary analysis of data from a randomized controlled trial conducted in three public hospitals in Adelaide. A total of 320 patients in hospital beds awaiting a residential aged care bed participated. Outcome measurements included HRQoL (Assessment of Quality of Life; AQoL), functional level (Modified Barthel Index), hospital readmission rates, survival, and place of residence at four months follow-up. RESULTS: In this frail group the median AQoL was poor at baseline (median 0.02; 95%CI -0.01 - 0.04) and at follow-up (0.05; 95%CI 0.03 - 0.06). On leaving hospital, more than one third of participants who were moving for the first time into nursing home care rated themselves in a state worse than death (AQoL < or = 0.0). Poor HRQoL at discharge from hospital (AQoL < or = 0.0) was a significant predictor of mortality (HR 1.7; 95%CI 1.2 - 2.7), but not hospital readmission nor place of residence at four months follow-up. Improved function was a predictor of improved HRQoL among the surviving cohort. CONCLUSION: People making the transition to residential aged care from hospital have very poor HRQoL, but small gains in function seem to be related to improvement. While functional gains are unlikely to change discharge destination in this frail group, they can contribute to improvements in HRQoL. These gains may be of great significance for individuals nearing the end of life and should be taken into account in resource allocation.Lynne C. Giles, Graeme Hawthorne and Maria Crott

Development and validation of a short version of the Partnership Self-Assessment Tool (PSAT) among professionals in Dutch disease-management partnerships

Background: The extent to which partnership synergy is created within quality improvement programmes in the Netherlands is unknown. In this article, we describe the psychometric testing of the Partnership Self-Assessment Tool (PSAT) among professionals in twenty-two disease-management partnerships participating in quality improvement projects focused on chronic care in the Netherlands. Our objectives are to validate the PSAT in the Netherlands and to reduce the number of items of the original PSAT while maintaining validity and reliability. Methods. The Dutch version of the PSAT was tested in twenty-two disease-management partnerships with 218 professionals. We tested the instrument by means of structural equation modelling, and examined its validity and reliability. Results: After eliminating 14 items, the confirmatory factor analyses revealed good indices of fit with the resulting 15-item PSAT-Short version (PSAT-S). Internal consistency as represented by Cronbach's alpha ranged from acceptable (0.75) for the 'efficiency' subscale to excellent for the 'leadership' subscale (0.87). Convergent validity was provided with high correlations of the partnership dimensions and partnership synergy (ranged from 0.512 to 0.609) and high correlations with chronic illness care (ranged from 0.447 to 0.329). Conclusion: The psychometric properties and convergent validity of the PSAT-S were satisfactory rendering it a valid and reliable instrument for assessing partnership syne

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world