Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

Two complementary iodoarene-catalyzed methods for the preparation of 2-oxazolines are presented. The first involves the cyclization of N-propargylamides and the second involves the cyclization of β-amidoketones. These are proposed to proceed through different mechanisms and have different substrate scopes

Dual oxidation/bromination of alkylbenzenes

In the presence of sodium bromide and Oxone, a range of alkylbenzene derivatives are brominated and/or oxidized with up to four C-H bonds being functionalized

Preparation and Synthetic Utility of Stable 1,3-Enynyl- and 1,3-Dienyl(aryl)iodonium Salts

The facile synthesis of stable enynyl- and dienyl(aryl)iodonium salts is achieved from terminal enynes. An X-ray crystal structure of an example of the latter is presented. These compounds are shown to be useful in a range of transformations

Computational study on the iodobenzene-catalyzed oxidative cyclization of a δ-alkynyl β-ketoester

The iodobenzene-catalyzed oxidative cyclization of a δ-alkynyl β-ketoester has been investigated by density functional theory (DFT) calculations at the CPCM(acetonitrile)/B3LYP/6-311++G(d,p)//B3LYP/SDD(I) levels. Three different mechanisms were considered for this process, and of the three, activation of the alkyne by a hypervalent iodine species followed by cyclization was found to be the most likely pathway based upon our computational results

Iodoarene-Catalyzed Cyclizations of Unsaturated Amides

The cyclization of N-alkenylamides catalyzed by iodoarenes under oxidative conditions is presented. Five-, six-, and seven-membered rings with a range of substitutions can be prepared by this route. Preliminary data from the use of chiral iodoarenes as precatalysts show that enantiocontrol is feasible

Studies on the Pd-Catalyzed Dimerization of Silacyclobutanes

Dimerization of silacyclobutanes has been achieved under palladium catalysis at room temperature. A previous report described the requirement for high temperature and a stoichiometric amount of palladium complex to effect this process

Venture funding for science-based African health innovation

<p>Abstract</p> <p>Background</p> <p>While venture funding has been applied to biotechnology and health in high-income countries, it is still nascent in these fields in developing countries, and particularly in Africa. Yet the need for implementing innovative solutions to health challenges is greatest in Africa, with its enormous burden of communicable disease. Issues such as risk, investment opportunities, return on investment requirements, and quantifying health impact are critical in assessing venture capital’s potential for supporting health innovation. This paper uses lessons learned from five venture capital firms from Kenya, South Africa, China, India, and the US to suggest design principles for African health venture funds.</p> <p>Discussion</p> <p>The case study method was used to explore relevant funds, and lessons for the African context. The health venture funds in this study included publicly-owned organizations, corporations, social enterprises, and subsidiaries of foreign venture firms. The size and type of investments varied widely. The primary investor in four funds was the International Finance Corporation. Three of the funds aimed primarily for financial returns, one aimed primarily for social and health returns, and one had mixed aims. Lessons learned include the importance of measuring and supporting both social and financial returns; the need to engage both upstream capital such as government risk-funding and downstream capital from the private sector; and the existence of many challenges including difficulty of raising capital, low human resource capacity, regulatory barriers, and risky business environments. Based on these lessons, design principles for appropriate venture funding are suggested.</p> <p>Summary</p> <p>Based on the cases studied and relevant experiences elsewhere, there is a case for venture funding as one support mechanism for science-based African health innovation, with opportunities for risk-tolerant investors to make financial as well as social returns. Such funds should be structured to overcome the challenges identified, be sustainable in the long run, attract for-profit private sector funds, and have measurable and significant health impact. If this is done, the proposed venture approach may have complementary benefits to existing initiatives and encourage local scientific and economic development while tapping new sources of funding.</p

Hidden in the Middle : Culture, Value and Reward in Bioinformatics

Bioinformatics - the so-called shotgun marriage between biology and computer science - is an interdiscipline. Despite interdisciplinarity being seen as a virtue, for having the capacity to solve complex problems and foster innovation, it has the potential to place projects and people in anomalous categories. For example, valorised 'outputs' in academia are often defined and rewarded by discipline. Bioinformatics, as an interdisciplinary bricolage, incorporates experts from various disciplinary cultures with their own distinct ways of working. Perceived problems of interdisciplinarity include difficulties of making explicit knowledge that is practical, theoretical, or cognitive. But successful interdisciplinary research also depends on an understanding of disciplinary cultures and value systems, often only tacitly understood by members of the communities in question. In bioinformatics, the 'parent' disciplines have different value systems; for example, what is considered worthwhile research by computer scientists can be thought of as trivial by biologists, and vice versa. This paper concentrates on the problems of reward and recognition described by scientists working in academic bioinformatics in the United Kingdom. We highlight problems that are a consequence of its cross-cultural make-up, recognising that the mismatches in knowledge in this borderland take place not just at the level of the practical, theoretical, or epistemological, but also at the cultural level too. The trend in big, interdisciplinary science is towards multiple authors on a single paper; in bioinformatics this has created hybrid or fractional scientists who find they are being positioned not just in-between established disciplines but also in-between as middle authors or, worse still, left off papers altogether

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe