This work is devoted to optimization of the synthesis of γ-S-carboxyethyl monomers of PNA based on L-Glu. PNA are promising compounds that hybridize with DNA or RNA, and due to their properties they are used in molecular biology, personalized medicine, and can also be used to create nanomaterials. To increase the yield of the desired monomers, it has been proposed to replace the benzyl protecting group with the carboxy function of the side radical by cyclohexyl one. Two synthetic schemes were proposed. In the first of them, γ-benzyl-N-Boc-glutamic acid, which was reduced to β-amino alcohol, was the starting compound. The hydroxyl group was protected by a dimethyl-tert-butylsilyl group. The benzyl ester in the side radical was cleaved by reduction on a palladium catalyst using ammonium formate. However, the subsequent acylation of cyclohexyl alcohol failed. In the second of the proposed schemes, a known sequence of reactions was used, which led to the formation of a cyclic derivative of Cbz-protected glutamic acid. Then, the resulting compound was acylated with cyclohexyl alcohol to give the desired ester. The subsequent transformation of the protective groups of the ester resulted in the diprotected L-glutamic acid in three stages. Subsequent reduction gave the desired protected β-amino alcohol containing a cyclohexyl protecting group in the side radical. This compound was further used in the Mitsunobu reaction to obtain a completely protected core of the PNA monomer. Subsequent thiolysis reaction resulted in the formation of the target secondary amine, the stability of which substantially exceeded the stability of its analog with benzyl protection, obtained and investigated before. The structure of the new compounds obtained is confirmed by 1H-NMR spectroscopy.

The solid-phase synthesis of a tetrameric model sequence of polyamide nucleic acid mimetics (PANAM) incorporating terminal chiral and charged unit was performed. As a result during the synthesis and cleavage from the resin the tendency of PANAM with the N-terminal negatively charged monomer to cyclization with simultaneous N-acyl transfer of carboxyethyl base residue was found. Application of MALDI-TOF mass - spectrometry allowed us to find suitable conditions for obtaining PANAM oligomers without the significant amount of by-products.

An approach for the determination of enantiomeric purity of chiral monomers of α-polyamide mimetics of nucleic acids is described. The test consisted of three steps: synthesis of each monomer as a racemic mixture from DL-Glu or DL-Ala, then selection of an eluent system for direct enantiomers separation on chiral phase by HPLC, and subsequent estimation of the amount of the major enantiomer obtained from L-Ala or L-Glu

Solid-phase Boc-protocol and synthetic strategy of negatively charged peptide nucleic acids has been suggested. New thymine containing negatively charged PNA decamer based on L-glutamic acid and glycine was synthesized.

The synthesis of pharmacologically active 2'-deoxynucleoside analog, namely, 2',3'-dideoxythymidine (I) and 3'-fluoro-3'-deoxythymidine (II) is described. The proposed approach consist in the condensation of corresponding thioglycosides with silylated thymine using N-bromosuccinimide as a promoter. In the case of compound II, it was shown that the yield and stereoselectivity of this process depend on the equivalent ratio of silylated base and solvent.

The synthesis of a thymin-containing monomer of negatively charged PNAs from L-glutamic acid derivatives is described. Two approaches to pseudopeptide backbone creation were realized: (i) reaction of reductive N-alkylation and (ii) Mitsunobu condensation. It is shown that the latter pathway is more favorable.

Several retinoids with modified polar group were synthesized. Biological screening using HL-60 promyelocyte leukemia cells showed that the free carboxyl in the retinoid molecules is not the only group responsible for exhibiting the differentiating activity.