ABSTRACT
Carbocyclic C-nucleosides are quite rare. Our route enables flexible preparation of three classes of these nucleoside analogs from common precursors-properly substituted cyclopentanones, which can be prepared racemic (in six steps) or optically pure (in ten steps) from inexpensive norbornadiene. The methodology allows flexible manipulation of individual positions around the cyclopentane ring, namely highly diastereoselective installation of carbo- and heterocyclic substituents at position 1', orthogonal functionalization of position 5', and efficient inversion of stereochemistry at position 2'. Newly prepared carbocyclic C-analog of tubercidine, profiled in MCF7 (breast cancer) and HFF1 (human foreskin fibroblasts) cell cultures, is less potent than tubercidine itself, but more selectively toxic toward the tumorigenic cells.
Subject(s)
Cyclopentanes/pharmacology , Nucleosides/pharmacology , Cell Proliferation/drug effects , Cells, Cultured , Cyclopentanes/chemical synthesis , Cyclopentanes/chemistry , Humans , Molecular Structure , Nucleosides/chemical synthesis , Nucleosides/chemistry , StereoisomerismABSTRACT
Many serious diseases are associated with degenerative changes caused by oxidative stress triggered by elevated concentrations of reactive oxygen species (ROS) in cells. Therefore, the development of suitable probes for monitoring such processes is of great importance. Here, we introduce a series of sulfur- and selenium-substituted BODIPY derivatives as reversible redox sensors for ROS and enzymatic redox processes. Significant differences in emission maxima and fluorescence quantum yields between the reduced and oxidized forms make them excellent ratiometric turn-on/off probes. Installation of polar sulfonate groups improved their aqueous solubility while retaining their sensing properties, which allowed the probes to monitor the enzymatic activity of enantioselective methionine sulfoxide reductase.