Development of a catalytic enantioselective synthesis of the guanacastepene and heptemerone tricyclic core

For nearly two decades, synthetic chemists have been fascinated by the structural complexity and synthetic challenges afforded by the guanacastepene and heptemerone diterpenoids. Numerous synthetic approaches to these compounds have been reported, but to date the application of enantioselective catalysis to this problem has not been realized. Herein we report an enantioselective synthesis of an advanced intermediate corresponding to the tricyclic core common to the guanacastepenes and heptemerones. Highlights of this work include sequential Pd-catalyzed decarboxylative allylic alkylation reactions to generate the two all carbon quaternary stereocenters, the use of ring-closing metathesis to close the A ring in the presence of a distal allyl sidechain, and a regio- and diastereoselective oxidation of a trienol ether to introduce oxygenation on the A ring

Frequency Locked Microtoroid Optical Resonators as a Non-Invasive Tumor Biopsy Alternative

Whispering gallery mode optical resonators offer an unusual coupling of rapid response time and ultra-sensitive biological and chemical detection. We have improved the signal to noise ratio of microtoroid optical resonators ∼1000-fold over standard techniques by using laser frequency locking and have applied this to assay tumor progression in mice by sensing the low concentrations of exosomes, shed by tumor cells, in serum samples collected from the animals. Serum samples from normal or experimental mice cause no shift in the resonance wavelength of the microtoroids; however, after using antibodies toward specific tumor markers to sensitize the toroid surface, we detected changes in the resonance frequency of the microtoroid when exposed to the serum of tumor-implanted mice. Serum from control (tumor-free) mice caused no shift. The wavelength shifts observed were 600 times the noise and drift of the sensor, even for a million fold dilution of the serum sample. Analysis of the shifts showed unitary steps of ∼ 0.5 fm, suggesting that the assay may be sensitive enough to detect individual binding events, offering a means to analyze the size of the biomolecules that are binding to the resonator. If validated, this approach offers a non-invasive tumor “biopsy,” exploiting the circulation of blood to collect a sample of tumor surfaces without the need to find or access the tumors

Synthesis of enantioenriched γ-quaternary cycloheptenones using a combined allylic alkylation/Stork–Danheiser approach: preparation of mono-, bi-, and tricyclic systems

A general method for the synthesis of β-substituted and unsubstituted cycloheptenones bearing enantioenriched all-carbon γ-quaternary stereocenters is reported. Hydride or organometallic addition to a seven-membered ring vinylogous ester followed by finely tuned quenching parameters achieves elimination to the corresponding cycloheptenone. The resulting enones are elaborated to bi- and tricyclic compounds with potential for the preparation of non-natural analogs and whose structures are embedded in a number of cycloheptanoid natural products

Ring-Contraction Strategy for the Practical, Scalable, Catalytic Asymmetric Synthesis of Versatile γ-Quaternary Acylcyclopentenes

Contraction action! A simple protocol for the catalytic asymmetric synthesis of highly functionalized γ-quaternary acylcyclopentenes (see schematic) in up to 91 % overall yield and 92 % ee has been developed. The reaction sequence employs a palladium-catalyzed enantioselective alkylation reaction and exploits the unusual stability of β-hydroxy cycloheptanones to achieve a general and robust method for performing two-carbon ring contractions

Computer-Enhanced Visual Learning Method to Teach Endoscopic Correction of Vesicoureteral Reflux: An Invitation to Residency Training Programs to Utilize the CEVL Method

Herein we describe a standardized approach to teach endoscopic injection therapy to repair vesicoureteral reflux utilizing the CEVL method, an internet-accessed platform. The content was developed through collaboration of the authors' clinical and computer expertises. This application provides personnel training, examination, and procedure skill documentation through the use of online text with narration, pictures, and video. There is also included feedback and remediation of skill performance and teaching “games.” We propose that such standardized teaching and procedure performance will ultimate in improved surgical results. The electronic nature of communication in this journal is ideal to rapidly disseminate this information and to develop a structure for collaborative research

Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones

The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF_3)_3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee’s up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee

A Community in Bloom: An affordable housing needs assessment of West Bloomington

Purpose of Report This report was written in response to a request from Habitat for Humanity of McLean County. The report expands upon and updates an affordable homeownership needs assessment for the Bloomington-Normal community – with an emphasis on West Bloomington – that was created in 2004. Because the housing market and economic conditions of the area have changed drastically in the last 6 years, an updated report is necessary. Data Sources and Methodology This report uses a combination of primary and, mainly, secondary data sources. Interviews were conducted with representatives of, among others, Bloomington Housing Authority, the Economic Development Council (EDC) of Bloomington-Normal Area, Mid Central Community Action, Prairie State Legal Services, and the West Bloomington Revitalization Project. A variety of data were gathered from secondary sources, such as the U.S. Department of Housing and Urban Development (HUD), the U.S. Census, the City of Bloomington, the U.S. Bureau of Labor Statistics, Mid Central Community Action, the National Association of Realtors, and the National Low Income Housing Coalition (NLIHC)

Palladium-catalyzed asymmetric alkylation in the synthesis of cyclopentanoid and cycloheptanoid core structures bearing all-carbon quaternary stereocenters

General catalytic asymmetric routes toward cyclopentanoid and cycloheptanoid core structures embedded in numerous natural products have been developed. The central stereoselective transformation in our divergent strategies is the enantioselective decarboxylative alkylation of seven-membered β-ketoesters to form α-quaternary vinylogous esters. Recognition of the unusual reactivity of β-hydroxyketones resulting from the addition of hydride or organometallic reagents enabled divergent access to y-quaternary acylcyclopentenes through a ring contraction pathway or y-quaternary cycloheptenones through a carbonyl transposition pathway. Synthetic applications of these compounds were explored through the preparation of mono-, bi-, and tricyclic derivatives that can serve as valuable intermediates for the total synthesis of complex natural products. This work complements our previous work with cyclohexanoid systems

A pragmatic harm reduction approach to manage a large outbreak of wound botulism in people who inject drugs, Scotland 2015

Abstract Background People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date. Methods A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection. Results Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected. Conclusions The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID