Intermolecular Oxidopyrylium (5 + 2) Cycloaddition/Reductive Ring-Opening Strategy for the Synthesis of α-Methoxytropones.

α-Methoxytropone is a structural motif found in various natural products and other compounds of interest to the scientific community but remains a synthetic challenge. The present Note describes the synthesis of variously substituted α-methoxytropones and related compounds through an intermolecular 3-hydroxy-4-pyrone-based oxidopyrylium (5 + 2) cycloaddition followed by a samarium iodide-mediated reductive ring-opening. The strategy is highlighted in the synthesis of a novel AC-ring analogue of colchicine to compare it to existing methods.

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.

In vitro evaluation of tropolone absorption, metabolism, and clearance.

Tropolone compounds can inhibit hepatitis B virus (HBV) replication at sub-micromolar levels and are synergistic upon co-treatment with nucleos(t)ide analog drugs. However, only a few compounds within this chemotype have been screened for their pharmacological properties. Here, we chose 36 structurally diverse tropolones from six subclasses to characterize their in vitro pharmacological parameters.

Lactam-fused tropolones: a new tunable, environmentally sensitive fluorophore class.

Fluorescent small-molecules capable of altering their profiles in response to environmental changes are exceptionally valuable tool compounds throughout the scientific community. The following manuscriipt describes a new class of fluorescent small molecules based on lactam-fused tropolones that are responsive to a dynamic range of environmental changes. These molecules can be easily obtained through a rapid annulation procedure between appropriately functionalized tropolones and primary amines, which is often complete within minutes at room temperature.