Electrochemical Iodination through the In Situ Generation of Iodinating Agents: A Promising Green Approach.

The synthesis of iodinated compounds using cheap, simple, and green strategies is of fundamental importance. Iodination reactions are mainly used to synthesize useful intermediates, especially in the pharmaceutical field, where they are employed for the production of contrast media or of iodinated active pharmaceutical ingredients. Traditional synthetic methods suffer from the use of erosive, toxic, or hazardous reactants. Approaches which involve the use of molecular iodine as an iodinating agent require the addition of an oxidizing agent, which is often difficult to handle. Electrochemistry can offer a valid and green alternative by avoiding the addition of such oxidizing agents, transforming the iodine source in the active species through the use of electrons as the main reactants. Herein, we report the electrochemical iodination with the generation of iodinating species in situ in water by using iodides as the source of iodine atoms. First of all, the electrochemical behavior of iodide and iodine in water on carbonaceous anodes was studied and, after selecting the suitable potential, in situ electrochemical iodination was successfully applied to 5-hydroxyisophthalic acid and 5-sulfosalicylic acid, comparing the iodinating power of I2 and iodonium species.

Structure-Function Studies of Sponge-Derived Compounds on the Cardiac CaV3.1 Channel.

T-type calcium (CaV3) channels are involved in cardiac automaticity, development, and excitation-contraction coupling in normal cardiac myocytes. Their functional role becomes more pronounced in the process of pathological cardiac hypertrophy and heart failure. Currently, no CaV3 channel inhibitors are used in clinical settings. To identify novel T-type calcium channel ligands, purpurealidin analogs were electrophysiologically investigated. These compounds are alkaloids produced as secondary metabolites by marine sponges, and they exhibit a broad range of biological activities. In this study, we identified the inhibitory effect of purpurealidin I (1) on the rat CaV3.1 channel and conducted structure-activity relationship studies by characterizing the interaction of 119 purpurealidin analogs. Next, the mechanism of action of the four most potent analogs was investigated. Analogs 74, 76, 79, and 99 showed a potent inhibition on the CaV3.1 channel with IC50's at approximately 3 µM. No shift of the activation curve could be observed, suggesting that these compounds act like a pore blocker obstructing the ion flow by binding in the pore region of the CaV3.1 channel. A selectivity screening showed that these analogs are also active on hERG channels. Collectively, a new class of CaV3 channel inhibitors has been discovered and the structure-function studies provide new insights into the synthetic design of drugs and the mechanism of interaction with T-type CaV channels.