Enantiomeric Analysis of Chiral Isotopomers via Microwave Three-Wave Mixing.

Many achiral molecules can be made chiral by appropriate positioning of an isotope. Accurate detection of this type of chirality has remained elusive, and there is as yet no general method for detection of isotopically chiral species. Here, we present the first application of microwave three-wave mixing to isotopically chiral molecules, detecting enantiomeric excess in ( R/ S)-benzyl-α-D1 alcohol. Our method is expected to be applicable to a broad range of isotopically chiral molecules with a prochiral parent species.

Environmental exposures associated with honey bee health.

Bee health is declining on a global scale, yet the exact causes and their interactions responsible for the decline remain unknown. To more objectively study bee health, recently biomarkers have been proposed as an essential tool, because they can be rapidly quantified and standardized, serving as a comparable measure across bee species and varying environments. Here, we used a systems biology approach to draw associations between endogenous and exogenous chemical profiles, with pesticide exposure, or the abundance of the 21 most common honey bee diseases. From the analysis we identified chemical biomarkers for both pesticide exposure and bee diseases along with the mechanistic biological pathways that may influence disease onset and progression. We found a total of 2352 chemical features, from 30 different hives, sampled from seven different locations. Of these, a total of 1088 significant associations were found that could serve as chemical biomarker profiles for predicting both pesticide exposure and the presence of diseases in a bee colony. In almost all cases we found novel external environmental exposures within the top seven associations with bee diseases and pesticide exposures, with the majority having previously unknown connections to bee health. We highlight the exposure-outcome paradigm and its ability to identify previously uncategorized interactions from different environmental exposures associated with bee diseases, pesticides, mechanisms, and potential synergistic interactions of these that are responsible for honey bee health decline.

Increased alarm pheromone component is associated with Nosema ceranae infected honeybee colonies.

Use of chemicals, such as alarm pheromones, for rapid communication with conspecifics is widespread throughout evolutionary history. Such chemicals are particularly important for social insects, such as the honeybee (Apis mellifera), because they are used for collective decision-making, coordinating activities and self-organization of the group. What is less understood is how these pheromones change due to an infection and what the implications might be for social communication. We used semiquantitative polymerase chain reaction (sqPCR) to screen for a common microsporidian gut parasite, Nosema ceranae, for 30 hives, across 10 different locations. We then used high-resolution accurate mass gas chromatography-quadrupole time of flight mass spectrometry to generate an exposome profile for each hive. Of the 2352 chemical features identified, chemicals associated with infection were filtered for cosanes or cosenes. A significant association was found between N. ceranae and the presence of (Z)-11-eicosen-1-ol, a known alarm pheromone component. The increase in (Z)-11-eicosen-1-ol could be the recognition mechanism for healthy individuals to care for, kill, or quarantine infected nestmates. Nosema ceranae has contributed to the global decline in bee health. Therefore, altered alarm pheromones might play a role in disrupting social harmony and have potential impacts on colony health.

Silicone Wristbands as Passive Samplers in Honey Bee Hives.

The recent decline of European honey bees (Apis mellifera) has prompted a surge in research into their chemical environment, including chemicals produced by bees, as well as chemicals produced by plants and derived from human activity that bees also interact with. This study sought to develop a novel approach to passively sampling honey bee hives using silicone wristbands. Wristbands placed in hives for 24 h captured various compounds, including long-chain hydrocarbons, fatty acids, fatty alcohols, sugars, and sterols with wide ranging octanol-water partition coefficients (Kow) that varied by up to 19 orders of magnitude. Most of the compounds identified from the wristbands are known to be produced by bees or plants. This study indicates that silicone wristbands provide a simple, affordable, and passive method for sampling the chemical environment of honey bees.

Novel pyridine derivatives as potent and selective CB2 cannabinoid receptor agonists.

Replacement of the phenyl ring in our previous (morpholinomethyl)aniline carboxamide cannabinoid receptor ligands with a pyridine ring led to the discovery of a novel chemical series of CB2 ligands. Compound 3, that is, 2,2-dimethyl-N-(5-methyl-4-(morpholinomethyl)pyridin-2-yl)butanamide was identified as a potent and selective CB2 agonist exhibiting in vivo efficacy after oral administration in a rat model of neuropathic pain.

Correction: Honey bee (Apis mellifera) exposomes and dysregulated metabolic pathways associated with Nosema ceranae infection.

[This corrects the article DOI: 10.1371/journal.pone.0213249.].

Honey bee (Apis mellifera) exposomes and dysregulated metabolic pathways associated with Nosema ceranae infection.

Honey bee (Apis mellifera) health has been severely impacted by multiple environmental stressors including parasitic infection, pesticide exposure, and poor nutrition. The decline in bee health is therefore a complex multifactorial problem which requires a holistic investigative approach. Within the exposome paradigm, the combined exposure to the environment, drugs, food, and individuals' internal biochemistry affects health in positive and negative ways. In the context of the exposome, honey bee hive infection with parasites such as Nosema ceranae is also a form of environmental exposure. In this study, we hypothesized that exposure to xenobiotic pesticides and other environmental chemicals increases susceptibility to N. ceranae infection upon incidental exposure to the parasite. We further queried whether these exposures could be linked to changes in conserved metabolic biological pathways. From 30 hives sampled across 10 sites, a total of 2,352 chemical features were found via gas chromatography-time of flight mass spectrometry (GC-TOF) in extracts of honey bees collected from each hive. Of these, 20 pesticides were identified and annotated, and found to be significantly associated with N. ceranae infection. We further determined that infected hives were linked to a greater number of xenobiotic exposures, and the relative concentration of the exposures were not linked to the presence of a N. ceranae infection. In the exposome profiles of the bees, we also found chemicals inherent to known biological metabolic pathways of Apis mellifera and identified 9 dysregulated pathways. These findings have led us to posit that for hives exposed to similar chemicals, those that incur multiple, simultaneous xenobiotic stressors have a greater incidence of infection with N. ceranae. Mechanistically, our results suggests the overwhelming nature of these exposures negatively affects the biological functioning of the bee, and could explain how the decline in bee populations is associated with pesticide exposures.

Total synthesis of 12,13-desoxyepothilone B (Epothilone D).

A highly convergent total synthesis of 12,13-desoxyepothilone B (4, Epothilone D) is described involving the coupling of vinyl iodide (5) and olefin (6). Key steps in the synthesis are the introduction of chirality at C15 via highly enantioselective lipase-mediated enzymatic resolution, diastereoselective alkylation at C8, highly diastereoselective Evans aldol reaction to establish C6-C7, and Mukaiyama aldol reaction to introduce chiral center C3. Palladium catalyzed Suzuki coupling of (5) and (6) provided the methyl ester (27), which was converted to 12,13-desoxyepothilone B (4).

The synthesis of azapeptidomimetic beta-lactam molecules as potential protease inhibitors.

Synthetic methods for the construction of a novel peptidomimetic structure are reported. The structure incorporates a beta-lactam and an azapeptide in a peptide backbone with the intention of generating rationally designed substrate-based protease inhibitors. The beta-lactam is formed by subjecting serine or threonine-azapeptides to Mitsunobu reaction conditions. Importantly, the azapeptidomimetic beta-lactam structure permits extended binding inhibition and the synthetic methods to create tetrapeptidomimetic structures are described.