Scientists have developed a strategy that can promote the development of pyridine-containing drugs and organic functional materials.
In chemicals used in agriculture, as well as in pharmaceuticals and a variety of materials, pyridines are often found as functional units that critically determine the chemical properties of materials. Pyridines belong to the group of cyclic carbon-hydrogen (CH) compounds (“heterocycles”), and contain a nitrogen (N) atom. For chemists, the direct activation of carbon-hydrogen bonds (CH bonds) of pyridine is a straightforward approach to design and modification of complex molecules, including the final stage of the synthesis sequence.
The latter means that the active ingredients can be chemically modified without having to be rebuilt anew. The actuation of pyridine in a specific position with respect to the nitrogen atom—in the hard-to-reach “epi-position”—is extremely difficult and rare. A team of researchers headed by Professor Armido Studer at the Institute of Organic Chemistry at the University of Münster has developed a new strategy for inserting different functional groups into the epitaxial position of pyridines. Their study has now been published in the journal Sciences.
Chemists use temporary aromatization of pyridine: its electronic properties are reversed, resulting in a stable intermediate product – dynamin. By means of radical and polar chemistry, researchers can obtain, with a high degree of selectivity, a large number of fluorinated alkanes, as well as a series of “electron-deficient substituents” (electric compounds), in epitaxial position. These transformations also include related medical and agrochemical functions such as fluoromethyl chlorine and halogen groups. “The important thing is that functional dynamin intermediates can be readily re-odorized into meta-functionalized pyridines under acidic conditions,” says Dr. Hui Cao, a postdoctoral researcher in Studer’s work group.
His colleague Dr. Chiang Cheng adds, “The high degree of efficacy, wide range of applications, and meta-selectivity of our approach enables the employment of twelve different types of drugs.” In addition, the team has developed processes by which drugs can be converted directly into trifluoromethyl and chlorine-substituted derivatives — in so-called one-pot reactions, which require little effort and occur in a single reaction vessel. For this purpose, chemists use inexpensive, commercially available reagents. “Our study provides an answer to an unsolved problem of activation of pyridine in the epitaxial position,” says Armido Studer. “We believe that this publication will give a great impetus to the development of drugs containing pyridine and organic functional substances.”