Combinatorial Chemistry in Higher School: Ten-Year Experience of Research, Educational, and Managerial Projects // Journal of General Chemistry, 2010, Vol. 80, No. 12, 2655-2670 (Original: Rossiiskii Khimicheskii Zhurnal, 2009, Vol. 53, No. 5, pp.140-152)

Short overview is given of the author’s group activities over the last decade in the research, educational and other projects related to combinatorial chemistry. The discovery of novel reactions and classes of heterocyclic scaffolds (oxazoles, indolizines, and imidazoles) led to new libraries, for which different types of biological activity (antimicrobial, adrenergic, anxiolytic, and anti-protozoal) was predicted and experimentally confirmed. Education of students at the Moscow State University with practical combinatorial chemistry course is reviewed, as well as other initiatives related to promotion of combinatorial chemistry in Russia. The progress of combinatorial chemistry in Russia is directly related to the problem of survival of domestic science (development of material basis, preservation of human resources), adaptation of basic science to practice, and search for optimum interaction between researchers and consumers of the final product. In Russia, no balance has yet been found in this field between university science and consumers’ demand (state and private), unlike what is already true of foreign countries. This is just the reason why the available experience in combinatorial R&D is not only of historical interest, but also can form the basis for further development. The aim of the present publication is to give a brief review of research, applied, and educational and managerial projects associated with combinatorial chemistry and fulfilled over the past decade by our research group at the Chemical Department of the Moscow State University (MSU). In the first part we will dwell on the experience in the implementation of fairly abstract synthetic ideas into practical projects and in the second, approaches to teaching and promotion of combinatorial chemistry in Russia. Certain Applied Aspects of Basic Heterocyclic Chemistry Over a long time our research effort has been focused on bridged azolazines I–III (Scheme 1). The parent structure in this family is indolizine I which can be considered as a superposition of pyrrole and pyridine, two key archetypes of heterocyclic chemistry as a whole. Indolizines are isomeric and isostructural to indoles (certain некоторые indolizines can even be rearranged into indoles), which induced out interest in this subclass. In developing synthetic approaches to functionalized indolizines we discovered a number of new and quite unusual (structurally) types of cyclizations and rearrangements where the precursors of compounds I were cationoid II or mesoionic III azolopyridines, as well as pyridinium salts IV. Our long-standing research program [1] involved study of methods of synthesis and genetic interrelationships of compounds of classes I–IV, as well as use of these compounds as precursors of heterocyclic systems V [2–5]. Over the course of this research we synthesized hundreds of new compounds belonging to previously unknown subclasses of substituted heterocycles. Obviously, this research is quite indirectly related to immediate problems of combinatorial chemistry. Radically new compound classes could at best enrich abundant combinatorial collections of “historical libraries,” where a new structural type would contributed to the diversity of structural motifs. (In this case, a new compound will probably be demanded in the framework of a narrow-focus project, for example, DOI: 10.1134/S1070363210120315