STUDY OF BIOLOGICAL ACTIVITY OF RACEMIC AND OPTICALLY ACTIVE ESTERS OF NAPHTHENIC AND FATTY ACIDS BASED ON UNSATURATED OXYESTERS

Petrochemical products based on petroleum naphthenic acids have special properties. Esters of naphthenic acids possess practically valuable organic compounds. The aim of this work is the development of effective methods for the preparation of aromatic esters based on naphthenic and individual fatty acids which is a very promising direction in the medicine practice. The synthesis of unsaturated racemic and chiral oxyethers was carried out on the basis of the interaction of chloromethylpropargyl (allyl) esters with carbonyl compounds with the participation of metallic zinc. Also, to study the biological activity, racemic and optically active esters were synthesized based on naphthenic acids and unsaturated racemic and chiral oxyesters. As test cultures used: gram-positive (Staphylo-coccus aureus-Staphylococcus aureus), gram-negative (Pseudomonas aeruginosa – Pseu-domonas aeruginosa, Escherichia coli) bacteria, as well as yeast-like fungi of the genus Candida - Candida albicans. Analysis of the biological activity of the synthesized compounds showed that optically active bicyclo [2.2.1] hept-5-ene-2-methylol monoesters have higher antimicrobial and antifungal activity compared to their racemic analogs and drugs used in medicine.

Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms

Allylation of nucleophiles with highly reactive electrophiles like allyl halides can be conducted without metal catalysts. Less reactive electrophiles, such as allyl esters and carbonates, usually require a transition metal catalyst to facilitate the allylation. Herein, we report a unique transition-metal-free allylation strategy with allyl ether electrophiles. Reaction of a host of allyl ethers with 2-azaallyl anions delivers valuable homoallylic amine derivatives (up to 92%), which are significant in the pharmaceutical industry. Interestingly, no deprotonative isomerization or cyclization of the products were observed. The potential synthetic utility and ease of operation is demonstrated by a gram scale telescoped preparation of a homoallylic amine. In addition, mechanistic studies provide insight into these C(sp3)–C(sp3) bond-forming reactions.

Ruthenium-catalyzed formal sp3 C–H activation of allylsilanes/esters with olefins: efficient access to functionalized 1,3-dienes

Ru-catalysed oxidative coupling of allylsilanes and allyl esters with activated olefins has been developed via isomerization followed by C(allyl)–H activation providing efficient access to stereodefined 1,3-dienes in excellent yields.

Global Diastereoconvergence in the Ireland–Claisen Rearrangement of Isomeric Enolates: Synthesis of Tetrasubstituted -Amino Acids

<div><div><div><p>A dual experimental/theoretical investigation of the Ireland–Claisen rearrangement of tetrasubstituted a-phthalimido ester enolates to afford a-tetrasubstituted, b-trisubstituted a-amino acids (generally >20:1 dr) is described. For trans allylic olefins, the Z and E-enol ethers proceed through chair and boat transition states, respectively. For cis allylic olefins, the trend is reversed. As a result, the diastereochemical outcome of the reaction is preserved regardless of the geometry of the enolate or the accompanying allylic olefin. We term this unique convergence of all possible olefin isomers as global diastereoconvergence. This reaction manifold circumvents limitations in present-day technologies for the stereoselective enolization of a,a-disubstituted allyl esters. Density func- tional theory paired with state-of-the-art local coupled-cluster theory (DLPNO-CCSD(T)) was employed for the accurate determina- tion of quantum mechanical energies.</p></div></div></div>

Global Diastereoconvergence in the Ireland–Claisen Rearrangement of Isomeric Enolates: Synthesis of Tetrasubstituted -Amino Acids

<div><div><div><p>A dual experimental/theoretical investigation of the Ireland–Claisen rearrangement of tetrasubstituted a-phthalimido ester enolates to afford a-tetrasubstituted, b-trisubstituted a-amino acids (generally >20:1 dr) is described. For trans allylic olefins, the Z and E-enol ethers proceed through chair and boat transition states, respectively. For cis allylic olefins, the trend is reversed. As a result, the diastereochemical outcome of the reaction is preserved regardless of the geometry of the enolate or the accompanying allylic olefin. We term this unique convergence of all possible olefin isomers as global diastereoconvergence. This reaction manifold circumvents limitations in present-day technologies for the stereoselective enolization of a,a-disubstituted allyl esters. Density func- tional theory paired with state-of-the-art local coupled-cluster theory (DLPNO-CCSD(T)) was employed for the accurate determina- tion of quantum mechanical energies.</p></div></div></div>

Synthesis and Cytotoxicity Evaluation of DOTA-Conjugates of Ursolic Acid

In this study, we report the synthesis of several amine-spacered conjugates of ursolic acid (UA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Thus, a total of 11 UA-DOTA conjugates were prepared holding various oligo-methylene diamine spacers as well as different substituents at the acetate units of DOTA including tert-butyl, benzyl, and allyl esters. Furthermore, three synthetic approaches were compared for the ethylenediamine-spacered conjugate 29 regarding reaction steps, yields, and precursor availability. The prepared conjugates were investigated regarding cytotoxicity using SRB assays and a set of human tumor cell lines. The highest cytotoxicity was observed for piperazinyl spacered compound 22. Thereby, EC50 values of 1.5 µM (for A375 melanoma) and 1.7 µM (for A2780 ovarian carcinoma) were determined. Conjugates 22 and 24 were selected for further cytotoxicity investigations including fluorescence microscopy, annexin V assays and cell cycle analysis.

Application of Lecitase® Ultra-Catalyzed Hydrolysis to the Kinetic Resolution of (E)-4-phenylbut-3-en-2-yl Esters

The possibility of using Lecitase® Ultra as a novel alternative biocatalyst for the kinetic resolution of model racemic allyl esters of (E)-4-phenylbut-3-en-3-ol: Acetate (4a) and propionate (4b) through their enantioselective hydrolysis was investigated. Reaction afforded (+)-(R)-alcohol (3) and unreacted (−)-(S)-ester (4a or 4b). Hydrolysis of propionate 4b proceeded with higher enantioselectivity than acetate 4a. (R)-Alcohol (3) with highest enantiomeric excess (93–99%) was obtained at 20–30 °C by hydrolysis of propionate 4b, while the highest optical purity of unreacted substrate was observed for (S)-acetate 4a (ee = 34–56%). The highest enantioselectivity was found for the hydrolysis of propionate 4b catalyzed at 30 °C (E = 38). Reaction carried out at 40 °C significantly lowered enantiomeric excess of produced alcohol 3 and enantioselectivity in resolution. Lecitase® Ultra catalyzed the enantioselective hydrolysis of allyl esters 4a,b according to Kazlauskas’ rule to produce (R)-alcohol 3 and can find application as a novel biocatalyst in the processes of kinetic resolution of racemic allyl esters.