Hryhorenko O. Сyclic amino acids, their derivatives and analogues – sourses of compounds for drug discovery.

In the thesis, synthetic approaches to lead-like compounds and tools for their theoretical investigation are discussed, i.e. methodology towards realization of lead-oriented synthesis is proposed. In particular, it is shown that cyclic amino acids, their derivatives and analogues are promising lead-oriented building blocks for drug discovery, and synthetic strategies are defined for each type of the aforementioned compounds. An efficient approach to Boc-protected 4,5-methano-β-proline – a bicyclic cyclopropane-containing amino acid – is developed starting from easily available itaconic acid. The proposed method allowes to prepare of both cis- and trans-isomers of the title compound; it can be used at gram scale. Meanwhile, an approach to scalable synthesis of methyl 5-oxopyrrolidine-3-carboxylate – the key intermediate in the synthetic scheme – is developed. An approach to both racemic and enantiopure (1R,6S)-3,4-methanonipecotic acid bearing a cyclopropane moiety is developed. The method proposed for the enantiopure compound includes 12 steps; a shorter approach to racemic 3,4-methanonipecotic acid is based on the Simmons – Smith cyclopropanation.