Aminonaphthalene 2‑Cyanoacrylate (ANCA) Probes Fluorescently Discriminate between Amyloid‑β and Prion Plaques in Brain

A major challenge for diagnosing and monitoring the progression of amyloid-based diseases is the capability to distinguish between amyloid deposits that are associated with related, but distinctly different, diseases. Here, we demonstrate that aminonaphthalenyl 2-cyanoacrylate-based probes can fluorescently discriminate between different types of amyloid deposits in brain. The discriminating capability of these molecular rotors is due to the stabilization of the ground versus excited states of these probes as a function of the polarity of their microenvironment (i.e., within the binding pocket on the amyloid). This property makes it possible, for the first time, to estimate the inherent static relative permittivity (ε₀) of the binding pocket of each amyloid within tissue. The capability to selectively follow the deposition of specific amyloids in tissue may provide important information for therapeutic development that is not readily accessible from currently available technology

An Unusual Michael-Induced Skeletal Rearrangement of a Bicyclo[3.3.1]nonane Framework of Phloroglucinols to a Novel Bioactive Bicyclo[3.3.0]octane

A novel skeletal rearrangement of bicyclo[3.3.1]nonane-2,4,9-trione (<b>16</b>) to an unprecedented highly functionalized bicyclo[3.3.0]octane system (<b>17</b>), induced by an intramolecular Michael addition, is presented. This novel framework was found to be similarly active to hyperforin (<b>1</b>), against PC-3 cell lines. A mechanistic study was examined in detail, proposing a number of cascade transformations. Also, reactivity of the Δ^7,10-double bond was examined under several conditions to explain the above results

An Unusual Michael-Induced Skeletal Rearrangement of a Bicyclo[3.3.1]nonane Framework of Phloroglucinols to a Novel Bioactive Bicyclo[3.3.0]octane

A novel skeletal rearrangement of bicyclo[3.3.1]nonane-2,4,9-trione (<b>16</b>) to an unprecedented highly functionalized bicyclo[3.3.0]octane system (<b>17</b>), induced by an intramolecular Michael addition, is presented. This novel framework was found to be similarly active to hyperforin (<b>1</b>), against PC-3 cell lines. A mechanistic study was examined in detail, proposing a number of cascade transformations. Also, reactivity of the Δ^7,10-double bond was examined under several conditions to explain the above results