RESUMEN
In this study, a series of halogen-substituted thioxanthenes were synthesized because the most important and biologically active derivatives of xanthenes are thioxanthenes. In order to obtain new thioxanthene derivatives, first, the starting molecules were synthesized by the appropriate reaction methods in two steps. The intramolecular Friedel-Crafts alkylation (FCA) method was used to convert the prepared three aromatic substituted starting alcohol compounds to their corresponding thioxanthenes by cyclization. For the intramolecular FCA reaction of secondary alcohols, which are the starting compounds (1a-1t), organic BroÌ·nsted acids, which require more innovative, easier, and suitable reaction conditions, were used instead of halide reagents with corrosive effects as classical FCA catalysts. Trifluoroacetic acid was determined to be the organocatalyst with the best yield. Therefore, some original 9-aryl/alkyl thioxanthene derivatives (2a-2t) were synthesized using the optimized FCA method. In addition, a new sulfone derivative of thioxanthene 3i was prepared by performing the oxidation reaction with one of the obtained new thioxanthene 2i. Thioxanthenes and their derivatives are important heterocyclic structures that contain pharmacologically valuable sulfur and are used in the treatment of psychotic diseases such as Alzheimer's or schizophrenia, as well as a number of potent biological activities.
RESUMEN
Chiral 1,3-diols are highly valuable molecules used in industries such as pharmaceuticals, cosmetics, and agriculture. Therefore, in this study, a new strategy was developed to synthesize enantiomerically pure (>99% ee) 1,3-diols. New chiral 1,3-diols (5a-5q) with high enantiomeric purity were synthesized from aldol products chiral 1,3-keto alcohols (4a-4q), which are aldol products with different structures. Chiral 1,3-keto alcohols (4a-4q) were synthesized by a new asymmetric aldol method in the first step. This method was developed using a new proline-derived organocatalyst (3g) and Cu(OTf)2 as an additive in DMSO-H2O for the first time. Almost >99% ee was obtained using our developed aldol procedure. In the second step, original chiral diols (5a-5q) of high enantiomeric purity were obtained by asymmetric reduction of chiral keto alcohols with chiral oxazaborolidine reagents. In this way, a two-step asymmetric reaction was developed for chiral 1,3-diol enantiomers with high enantiomeric purity. The structures of all the original chiral compounds obtained were elucidated by infrared and nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis methods. Their enantiomeric excesses were determined by the chiral high-performance liquid chromatography method. Both keto alcohols and their corresponding chiral diols synthesized can be used as chiral starting materials and chiral source materials or intermediates in the synthesis of many biologically active molecules, or they can be used as chiral ligands in asymmetric synthesis, serving as organocatalysts.
RESUMEN
In this study, a new series of N-acyl hydrazones 7a-e, 8a-e, and 9a-e, starting from methyl δ-oxo pentanoate with different substituted groups 1a-e, were synthesized as anticancer agents. The structures of obtained target molecules were identified by spectrometric analysis methods (FT-IR, 11H NMR, 13C NMR, and LC-MS). The antiproliferative activity of the novel N-acyl hydrazones was evaluated on the breast (MCF-7) and prostate (PC-3) cancer cell lines by an MTT assay. Additionally, breast epithelial cells (ME-16C) were used as reference normal cells. All newly synthesized compounds 7a-e, 8a-e, and 9a-e exhibited selective antiproliferative activity with high toxicity to both cancer cells simultaneously without any toxicity to normal cells. Among these novel N-acyl hydrazones, 7a-e showed the most potent anticancer activities with IC50 values at 7.52 ± 0.32-25.41 ± 0.82 and 10.19 ± 0.52-57.33 ± 0.92 µM against MCF-7 and PC-3 cells, respectively. Also, molecular docking studies were applied to comprehend potential molecular interactions between compounds and target proteins. It was seen that the docking calculations and the experimental data are in good agreement.
RESUMEN
In this work, new derivatives (substituted 9-methyl-9-arylxanthenes) of xanthene compounds (5a-l) of possible biological significance were synthesized by developing a new synthesis method. In order to obtain xanthene derivatives, the original alkene compounds to be used as the starting materials were synthesized in four steps using appropriate reactions. A cyclization reaction by intramolecular Friedel-Crafts alkylation was carried out in order to synthesize the desired xanthene derivatives using the alkenes as starting compounds. The intramolecular Friedel-Crafts reaction was catalyzed by trifluoroacetic acid (TFA) and provided some novel substituted 9-methyl-9-arylxanthenes with good yields at room temperature within 6-24 hours. As a result, an alkene compound was used for activation with TFA in the synthesis of xanthene through intramolecular Friedel-Crafts alkylation for the first time.