The Total Synthesis of (–)-Scabrolide A

The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels–Alder reaction and an enone–olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5–6–7] linear carbocyclic core of the molecule and complete the total synthesis

Enantioselective Total Synthesis of Nigelladine A via Late-Stage C–H Oxidation Enabled by an Engineered P450 Enzyme

An enantioselective total synthesis of the norditerpenoid alkaloid nigelladine A is described. Strategically, the synthesis relies on a late-stage C–H oxidation of an advanced intermediate. While traditional chemical methods failed to deliver the desired outcome, an engineered cytochrome P450 enzyme was employed to effect a chemo- and regioselective allylic C–H oxidation in the presence of four oxidizable positions. The enzyme variant was readily identified from a focused library of three enzymes, allowing for completion of the synthesis without the need for extensive screening

The Total Synthesis of (–)-Scabrolide A

The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels–Alder reaction and an enone–olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5–6–7] linear carbocyclic core of the molecule and complete the total synthesis

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

Prevalence of Hepatitis B Virus (HBV) Infection Among Hmong Immigrants in the San Joaquin Valley

Chronic hepatitis B infection (HBV) is the major cause of primary liver cancer worldwide and Asians are disproportionately affected. The prevalence of HBV among most Asian American groups has been well documented, except in Hmong immigrants in the United States. The aim of this study was to determine the prevalence of HBV among Hmong immigrants in the San Joaquin Valley of California. A convenient sample of 534 Hmong age ≥18 years was recruited at various locations throughout Fresno County. Blood samples from study participants were collected and tested for hepatitis B surface antigen (HBsAg) by enzyme-immunoassay. Two hundred and eighty-nine females and 245 males of Hmong descent (mean age, 43.93) were screened. Eighty-nine (41 males and 48 females) were positive for HBsAg, which accounts for a prevalence of 16.7% (95% C.I. 13.5–19.9). The majorities of HBsAg positive patients were ≥40 years (64.2%), married (66.7%), born in Laos (87.3%), and had lived in the United States ≥20 years (62.5%). Only 37.5% of the participants reported having a primary care physician. Our study revealed that approximately one out of every six Hmong immigrants screened was infected with HBV. Based on our findings, more than one-third of these infected patients have no primary care physician to provide further treatment, surveillance for liver cancer, or vaccination of their families. This supports the Institute of Medicine’s recent recommendations to the Center for Disease Control to engage in a national Hepatitis B surveillance system

Development of an ex vivo porcine lung model for studying growth, virulence, and signaling of Pseudomonas aeruginosa

Research into chronic infection by bacterial pathogens, such as Pseudomonas aeruginosa, uses various in vitro and live host models. While these have increased our understanding of pathogen growth, virulence, and evolution, each model has certain limitations. In vitro models cannot recapitulate the complex spatial structure of host organs, while experiments on live hosts are limited in terms of sample size and infection duration for ethical reasons; live mammal models also require specialized facilities which are costly to run. To address this, we have developed an ex vivo pig lung (EVPL) model for quantifying Pseudomonas aeruginosa growth, quorum sensing (QS), virulence factor production, and tissue damage in an environment that mimics a chronically infected cystic fibrosis (CF) lung. In a first test of our model, we show that lasR mutants, which do not respond to 3-oxo-C12-homoserine lactone (HSL)-mediated QS, exhibit reduced virulence factor production in EVPL. We also show that lasR mutants grow as well as or better than a corresponding wild-type strain in EVPL. lasR mutants frequently and repeatedly arise during chronic CF lung infection, but the evolutionary forces governing their appearance and spread are not clear. Our data are not consistent with the hypothesis that lasR mutants act as social “cheats” in the lung; rather, our results support the hypothesis that lasR mutants are more adapted to the lung environment. More generally, this model will facilitate improved studies of mi- crobial disease, especially studies of how cells of the same and different species interact in polymicrobial infections in a spatially structured environment

Asymmetric Synthesis of Quaternary Stereocenters via Metal Enolates

The strategy of using chiral metal enolate intermediates in a diverse variety of asymmetric transformations has allowed the generation of quaternary stereocenter-bearing products that are otherwise difficult to access. Many classic transformations including aldol, Mannich, conjugate addition, alkylation, and pericyclic-type reactions, as well as allylic alkylation and α-arylation/alkenylation, have been adapted to proceed through chiral metal enolate intermediates, allowing the asymmetric synthesis of many complex products in both an intermolecular and intramolecular manner. These transformations have proven useful in the synthesis of natural products and may also be applied to the synthesis of novel pharmaceuticals and other compounds of interest in the future. This review includes work done up to and including the year 2014

Asymmetric Synthesis of Quaternary Stereocenters via Metal Enolates

The strategy of using chiral metal enolate intermediates in a diverse variety of asymmetric transformations has allowed the generation of quaternary stereocenter-bearing products that are otherwise difficult to access. Many classic transformations including aldol, Mannich, conjugate addition, alkylation, and pericyclic-type reactions, as well as allylic alkylation and α-arylation/alkenylation, have been adapted to proceed through chiral metal enolate intermediates, allowing the asymmetric synthesis of many complex products in both an intermolecular and intramolecular manner. These transformations have proven useful in the synthesis of natural products and may also be applied to the synthesis of novel pharmaceuticals and other compounds of interest in the future. This review includes work done up to and including the year 2014