Iryna V. Mineyeva

Unsaturated lactones, (6R)- and (6S)-6-[(2R)-1,4-dioxaspiro[4.5]dec-2-yl]-4-methyl-5,6-dihydro-2H-pyran-2-ones, have been synthesized by diastereoselective allylation of (R)-2,3-O-cyclohexylidene­glycer­aldehyde with methyl 3-(bromomethyl)but-3-enoate and its allylstannyl derivative. These lactones have been subjected to highly diastereoselective reduction and utilized in a new retrosynthetic scheme for obtaining C⁵–C¹⁴, C¹⁵–C¹⁹, and C²⁰–C²⁶ building blocks of amphidinolide G and H families.

The possibility of diastereoselective allylation of (R)-2,3-O-cyclohexylideneglyceraldehyde with methyl 3-[(tributylstannyl)methyl]but-3-enoate and tributyl[2-(2,2-diethoxyethyl)prop-2-en-1-yl]stannane has been demonstrated for the first time. The obtained products have been used to synthesize unsaturated lactones, (6R)- and (6S)-6-[(2R)-1,4-dioxaspiro[4.5]decan-2-yl]-4-methyl-5,6-dihydro-2H-piran-2-ones, that are impor­tant building blocks for the preparation of the C¹–C⁸ fragment of amphidinolides C and F and pheromones of the spring hemlock looper Lambdina athasaria, the pitch pine looper Lambdina pellucidaria, and the coffee leaf miner Leucoptera coffeella.

Based on the reactions of diastereoselective allylation of (R)-2,3-O-cyclohexylideneelyceraldehyde with methyl 3-(bromomethyl)but-3-enoate and its allylstannyl derivative, unsaturated lactones (6R)- and (6S)-6-[(2R)-1,4-dioxaspiro[4.5]dec-2-yl]-4-methyl-5,6-dihydro-2H-pyran-2-ones were synthesized. After highly diastereoselective reduction, these lactones found application in the implementation of a new retrosynthetic scheme for the preparation of C–C, C–C and C–C building blocks of amphidinolides of the G and H families.

Modification of 2-acetyl-3H-benzo[f]chromen-3-one and 2-[(2E)-3-phenylprop-2-enoyl]-3H-benzo[f]chromen-3-one has been performed for the first time via the reaction with indole. The resulting benzo­[f]coumarins have been found to exhibit antioxidant properties in model systems: they react with hydrogen peroxide and sodium hypochlorite and regulate redox state of rat C6 glioma cells, which is reflected in reduced concentration of intracellular hydrogen peroxide and increased level of reduced glutathione. The synthesized compounds in the presence of exogenous hydrogen peroxide exert a protective effect on the cells, acting as antioxidants and restoring the redox balance. 2-[3-(1H-Indol-3-yl)-3-phenylpropanoyl]-3H-benzo[f]khromen-3-one at a micromolar concentrations inhibited the rat C6 glioma cell proliferation by 25–35%.

An efficient procedure has been developed for the synthesis of new heterocyclic compounds from 2-substituted functionalized allyl bromides as precursors to electrophilic and nucleophilic building blocks for 1,3-dicarbonyl compounds.

S-Allylation of 4-pentyl- and 4-[(1-acetoxycyclopropyl)methyl]-3,4-dihydropyrimidine-2(1H)-thiones with 2-functionalized allyl bromides available from cyclopropanol intermediates has been reported for the first time. New unique heterocyclic compounds structurally related to 3rd generation calcium channel blockers have been synthesized in high yields.

An efficient method has been developed for the synthesis of novel [1,3]thiazolo[3,2-a]pyrimidines containing a pentyl or 1-acetoxycyclopropylmethyl group at the 5-position. Potential biological activity of the synthesized compounds has been evaluated in silico by predicting their phospholipid bilayer permeability and by molecular docking to protein kinases and human acetylcholinesterase. Study of the effect of thiazolo­pyrimidines on the growth of Saccharomyces cerevisiae has shown the absence of acute toxicity of these com­pounds. (2Z)-6-Acetyl-2-(2-hydroxy-5-nitrobenzylidene)-7-methyl-5-pentyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-3(2H)-one exhibited antibacterial activity against Bacillus subtilis.

New isoxazoline derivatives have been synthesized in high yields by cycloaddition of acetonitrile oxide to α,β-unsaturated β-methyl-δ-lactones. These unsaturated lactones have been used to obtain β-methyl branched saturated lactones and lactams, as well as lactones with an inversed configuration of hydroxy group, following the divergent approach.

Efficient procedures have been developed for the allylation of structurally diverse ketones with methyl 3-(bromomethyl)but-3-enoates, and the possibility of using the allylation products in the target-oriented synthesis of new heterocyclic compounds has been demonstrated. Modification of benzo[f]coumarin derivatives at the keto group via Barbier allylation with methyl 3-(bromomethyl)but-3-enoate has been performed for the first time with the goal of subsequent formation of a lactone fragment. The synthesized benzo[f]coumarin derivatives have been characterized by spectral methods, and their ability to penetrate phospholipid bilayer has been estimated. These compounds have been found to affect neither viability nor proliferation of C6 rat glioma cells. The obtained benzo[f]coumarin derivatives exhibit antioxidant properties in model systems based on hydrogen peroxide and sodium hypochlorite.