A flexible approach to construct sterically congested bicyclo-alkenedione frameworks is reported. Under the action of potassium carbonate, α-sulphonyl cycloalkanones are added to functionalized allenyl esters, leading to a lactone intermediate that is subsequently reduced to initiate an intramolecular aldol cyclization to [3.2.1], [3.3.1], and [4.3.1] bicycles. Oxidation then affords bicyclic diones in good three-step yields. Under exceptionally mild conditions, these bicycles are converted to highly functionalized medium-sized rings through a Grob-type fragmentation.

While resveratrol protects organisms from the deleterious effects of oxidative stress, its multifarious mechanism of action limits its potential as a selective medicinal agent. To address this shortcoming, we have designed a molecular scaffold that we have termed a resveramorph. The structure of this compound class possesses much of the functional group characteristics of resveratrol but in a non-planar molecular arrangement and, in the present work, we probe the neuroprotective activities of two resveramorph analogs. These novel compounds were found to protect neurotransmission from hydrogen peroxide-induced oxidative stress. Our findings demonstrate that, at a subnanomolar level, one analog, resveramorph 1, protects synaptic transmission from acute oxidative stress at the Drosophila neuromuscular junction. These results position resveramorphs as potential lead compounds in the development of new drugs for neurodegenerative diseases.

An organic chemistry experiment is described that is based on recent research to elucidate a novel cation-π interaction between tetraalkammonium cations and propargyl hydrazines. This non-bonded interaction is a key component of the mechanism of ammonium-catalyzed intramolecular cycloaddition of nitrogen to the terminal carbon of a C-C triple bond of the propargyl substrate. In this teaching experiment, reactions and control experiments are employed to demonstrate the testing of two alternative mechanistic hypotheses. Specifically, cyclization reactions are performed with a soluble base (sodium phenoxide) with and without tetrabutylammonium bromide under homogeneous conditions. Students observe that the added ammonium salt accelerates the reaction. They are then encouraged to develop a testable hypothesis for the role of the ammonium salt in the cyclization mechanism: typical phase transfer or other. IR spectroscopy is then used to directly observe a dose dependent shift of the alkyne stretching mode due to a cation-π interaction. In this experiment, undergraduate “researchers” were able to practice the scientific method on a contemporary system and see how data are generated and interpreted to adjudicate between rival hypotheses in a way that emulates authentic and current research in a lab setting. This experimental design was tested on students enrolled in the introductory undergraduate Organic Chemistry Lab.

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The addition of allenyl esters (II) to -sulfonyl cycloalkanes (I) leads to lactones (III), which are converted into desired bicyclic diones (IV) by a reductive intramolecular aldol cyclization and a subsequent oxidation. The Bu 4NF--mediated fragmentation-decarboxylation reaction of diones (IV) affords cycloalkenones (V), whilst the fragmentation reaction with methanol gives rise to esters (VII). -(BHAT, B. A.; MAKI, S. L.; ST.GERMAIN, E. J.; MAITY, P.; LEPORE*, S. D.; J. Org. Chem. 79 (2014) 19, 9402-9407, http://dx.