Model compounds in stereochemistry, physical organic chemistry, medicinal chemistry and catalysis
Prof. Igor V. Komarov
The central theme of Prof. Komarov’s research group is medicinal chemistry and synthesis of model molecules, first of all those which can be used to get new knowledge in bioorganic chemistry, stereochemistry, theoretical chemistry, catalysis, etc. Special effort is put in the developing new synthetic methods. For example, synthesis of compound 1, which was used as a hapten to raise catalytic antibodies, required development of a simple method for P-C bond formation, and this was done in collaboration with Prof. A. J. Kirby from Cambridge University. Later, a number of model molecules have been synthesized: 2 (to study the reverse anomeric effect), 3, 4 (highly twisted amides), 5, 6 (stabilized tetrahedral intermediates), 7-9 (to study steric effects in glycoside transfer).
Another aspect of the research is asymmetric catalysis, again with the use of model molecules to study this extremely complex phenomenon (this work is a result of cooperation with Prof. Armin Boerner from University of Rostock). Compounds 10-15 were synthesized to study the influence of the oxygen-containing functional groups in chiral diphosphines on activity and selectivity of Rh-based hydrogenation catalysts based on them as ligands. Several good ligands were developed during this work, among them ROCKYPhos 16 (named after ROstock and KYjiv, the cities where the synthetic work and study was done, trade name CatASium I) was patented by Degussa – a cheap camphor-derived hydroxydiphosphine ligand which appears on market and is available on large scale.
Though the interest in asymmetric catalysis have not faded (recently Igor’s group developed highly efficient aminoalcohol ligands, for example 17), the research direction changed once more and now the research group is focused on synthesis of novel building blocks for drug design. The conformational restriction is a main design principle for the design of the building blocks. Presently, the group developed stereoselective routes to unknown conformationally restricted amino acids (e.g., 18), aiming at peptidomimetics based on them. Also Igor’s group is synthesizing fluorine-labeled rigid amino acids (compounds 19, 20 for example), to use them in NMR studies of peptides.
The scientific group of Prof. Komarov (left) consists of many talented ñandidates of ñhemical scientisis, PhD students and undergraduate students.