Synthetic, Computational, and Experimental Studies of a Class 3 Atropisomeric α-Naphthyl Tropone.

Atropisomerism is a stereochemical phenomenon that results from high configurational stability of chiral axes and is an important structural element in many functional molecules. Thus, understanding how different structural features can influence the stability of chiral axes can be an important consideration for molecular design. Recent studies have demonstrated that certain tropone-based chiral axes are significantly more stable than those of related benzenoids, likely a result of their relatively smaller external bond angles.

Patterns of systemic problems in Ghana's poultry value chain: A group model building approach.

Ghana's poultry sector faces different interrelated systemic challenges, often diagnosed in isolation, leading to interventions that neglect unintended consequences across the value chain. Consequently, a holistic prognosis of the impact of these systemic problems that considers the different facets of the poultry industry is required. This paper aims to examine the system archetypes emerging from the inherent industry-level and farm-level problems in Ghana's poultry sector.

Studies on the Configurational Stability of Tropolone-Ketone-, Ester-, and Aldehyde-Based Chiral Axes.

Recent studies have revealed that tropolone-amide aryl C-C(O) rotational barriers are dramatically higher than those of analogous benzamide-based systems, and as a result, they have an increased likelihood of displaying high configurational stability. Studies on other tropolone-based chiral axes are important to assess the generality of this phenomenon. Herein, we describe a series of studies on the rotational barriers of tropolone-ketone, tropolone-ester, and tropolone-aldehyde chiral axes.

Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis.

Objective: In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC 0-8h ). We characterized the pharmacogenetics of these interactions.

Metal coordinating inhibitors of Rift Valley fever virus replication.

Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales, whose replication depends on the enzymatic activity of the viral L protein.

Divergent synthesis of a thiolate-based α-hydroxytropolone library with a dynamic bioactivity profile.

Here we describe a rapid and divergent synthetic route toward structurally novel αHTs functionalized with either one or two thioether or sulfonyl appendages. Evaluation of this library against hepatitis B and herpes simplex virus, as well as the pathogenic fungus , and a human hepatoblastoma (HepDES19) revealed complementary biological profiles and new lead compounds with sub-micromolar activity against each pathogen.

KHF, a mild and selective desilylating agent for phenol -butyldimethylsilyl (TBDMS) ethers.

TBDMS (-BuMeSi, -butyldimethylsilyl) ethers of a variety of phenols have been deprotected with KHF in MeOH, at room temperature. Carboxylic ester and labile phenolic acetate were unaffected under these conditions. In competition reactions between TBDMS ethers of a phenol and two primary benzylic alcohols, the phenolic ether underwent cleavage whereas the alcohol ethers remained intact.

Efficacy and cytotoxicity in cell culture of novel α-hydroxytropolone inhibitors of hepatitis B virus ribonuclease H.

Chronic Hepatitis B virus (HBV) infection is a major worldwide public health problem. Current direct-acting anti-HBV drugs target the HBV DNA polymerase activity, but the equally essential viral ribonuclease H (RNaseH) activity is unexploited as a drug target. Previously, we reported that α-hydroxytropolone compounds can inhibit the HBV RNaseH and block viral replication.