Exploring Short and Efficient Synthetic Routes Using Titanocene(III)-Catalyzed Reactions: Total Synthesis of Natural Meroterpenes with Trisubstituted Unsaturations

This research was funded by FEDER (EDRF)/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades (P18-FR-2877), grant number A-FQM-079-UGR18.The stereo- and regioselective total syntheses of OMe derivatives of the scarce bioactive meroterpenoids makassaric acid (1) and fascioquinol B (2) have been accomplished. The synthetic sequences are based on the following three efficient and selective catalytic reactions: Cu-catalyzed addition of Grignard compounds to an epoxide; a regioselective Barbier-type reaction, catalyzed by Cp2TiCl; and regio- and stereoselective bioinspired cyclization, also catalyzed by Cp2TiCl. These three key processes allow us to obtain the main skeletons of 1 and 2 in a few steps. The valuable synthetic proposal shown in this work provides fast access to scarce, structurally complex meroterpenes with promising biological activities, which are a sustainable source for later studies and applications in medicine.FEDER (EDRF)/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades P18-FR-2877 A-FQM-079-UGR1

Synthesis and Biological Evaluation of Cassane Diterpene (5 alpha)-Vuacapane-8(14), 9(11)-Diene and of Some Related Compounds

A set of thirteen cassane-type diterpenes was synthesized and an expedient synthetic route was used to evaluate 14-desmethyl analogs of the most active tested cassane. The anti-inflammatory activities of these 13 compounds were evaluated on a lipopolysaccharide (LPS)-activated RAW 264.7 cell line by inhibition of nitric oxide (NO) production, some of them reaching 100% NO inhibition after 72 h of treatment. The greatest anti-inflammatory effect was observed for compounds 16 and 20 with an IC50 NO of 2.98 +/- 0.04 mu g/mL and 5.71 +/- 0.14 mu g/mL, respectively. Flow-cytometry analysis was used to determine the cell cycle distribution and showed that the inhibition in NO release was accompanied by a reversion of the differentiation processes. Moreover, the anti-cancer potential of these 13 compounds were evaluated in three tumor cell lines (B16-F10, HT29, and Hep G2). The strongest cytotoxic effect was achieved by salicylaldehyde 20, and pterolobirin G (6), with IC50 values around 3 mu g/mL in HT29 cells, with total apoptosis rates 80% at IC80 concentrations, producing a significant cell-cycle arrest in the G0/G1 phase, and a possible activation of the extrinsic apoptotic pathway. Additionally, initial SAR data analysis showed that the methyl group at the C-14 positions of cassane diterpenoids is not always important for their cytotoxic and anti-inflammatory activities.Junta de Andalucia BFQM-278-UGR20 B-FQM-650-UGR2

Synthesis of Tricyclic Pterolobirin H Analogue: Evaluation of Anticancer and Anti-Inflammatory Activities and Molecular Docking Investigations

This research was funded by grants from the Regional Government of Andalusia (Projects B-FQM-278-UGR20, B-FQM-650-UGR-20), and assistance was provided to the group FQM-348.Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules28176208/s1Pterolobirin H (3), a cassane diterpene isolated from the roots of Pterolobium macropterum, exhibits important anti-inflammatory and anticancer properties. However, its relatively complex tetracyclic structure makes it difficult to obtain by chemical synthesis, thus limiting the studies of its biological activities. Therefore, we present here a short route to obtain a rational simplification of pterolobirin H (3) and some intermediates. The anti-inflammatory activity of these compounds was assayed in LPS-stimulated RAW 264.7 macrophages. All compounds showed potent inhibition of NO production, with percentages between 54 to 100% at sub-cytotoxic concentrations. The highest anti-inflammatory effect was shown for compounds 15 and 16. The simplified analog 16 revealed potential NO inhibition properties, being 2.34 higher than that of natural cassane pterolobirin H (3). On the other hand, hydroxyphenol 15 was also demonstrated to be the strongest NO inhibitor in RAW 264.7 macrophages (IC50 NO = 0.62 ± 0.21 μg/mL), with an IC50NO value 28.3 times lower than that of pterolobirin H (3). Moreover, the anticancer potential of these compounds was evaluated in three cancer cell lines: HT29 colon cancer cells, Hep-G2 hepatoma cells, and B16-F10 murine melanoma cells. Intermediate 15 was the most active against all the selected tumor cell lines. Compound 15 revealed the highest cytotoxic effect with the lowest IC50 value (IC50 = 2.45 ± 0.29 μg/mL in HT29 cells) and displayed an important apoptotic effect through an extrinsic pathway, as evidenced in the flow cytometry analysis. Furthermore, the Hoechst staining assay showed that analog 15 triggered morphological changes, including nuclear fragmentation and chromatin condensation, in treated HT29 cells. Finally, the in silico studies demonstrated that cassane analogs exhibit promising binding affinities and docking performance with iNOS and caspase 8, which confirms the obtained experimental results.Regional Government of Andalusia B-FQM-278-UGR20, B-FQM-650-UGR-20, FQM-34

Evaluation of Anticancer and Anti-Inflammatory Activities of Some Synthetic Rearranged Abietanes

This research was funded by grants from the Regional Government of Andalusia (Projects B-FQM-278-UGR20, and B-FQM-650-UGR-20), and assistance was provided to the group FQM-348.Supplementary Materials: The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/ijms241713583/s1Synthesis of the rearranged abietane diterpenes pygmaeocins C and D, viridoquinone, saprorthoquinone, and 1-deoxyviroxocine has been successfully achieved. The anticancer and anti-inflammatory activities of selected orthoquinonic compounds 5, 7, 13, and 19, as well as pygmaeocin C (17), were evaluated for the first time. The antitumor properties were assessed using three cancer cell lines: HT29 colon cancer cells, Hep G2 hepatocellular carcinoma cells, and B16-F10 murine melanoma cells. Compounds 5 and 13 showed the highest cytotoxicity in HT29 cells (IC50 = 6.69 ± 1.2 µg/mL and IC50 = 2.7 ± 0.8 µg/mL, respectively). Cytometric studies showed that this growth inhibition involved phase S cell cycle arrest and apoptosis induction, possibly through the activation of the intrinsic apoptotic pathway. Morphological apoptotic changes, including nuclear fragmentation and chromatin condensation, were also observed. Furthermore, the anti-inflammatory activity of these compounds was evaluated on the basis of their ability to inhibit nitric oxide production on the lipopolysaccharide activated RAW 264.7 macrophage cell line. Although all compounds showed high anti-inflammatory activity, with percentages between 40 and 100%, the highest anti-inflammatory potential was obtained by pygmaeocin B (5) (IC50NO = 33.0 ± 0.8 ng/mL). Our results suggest that due to their dual roles, this type of compound could represent a new strategy, contributing to the development of novel anticancer agents.Regional Government of Andalusia B-FQM-278-UGR20, B-FQM-650-UGR-20, FQM-34

Exploring Potentialities and Limitations of Stapled o- Oligo(PhenyleneEthynylene)s (o-OPEs) as Efficient Circularly Polarized Luminescence Emitters

In this paper we have studied the chiroptical properties of a family of o-OPE derivatives with different steric hindrance. Experimental results show high dissymmetry factors (gabs and glum up to 1.1x10-2) and very similar ECD and CPL for all the derivatives, that makes this basic o-OPE scaffold a robust pure organic emitter. VCD spectra are used to characterize conformational properties in solution. DFT and TD-DFT calculations support experimental results also proving that ECD and CPL are almost exclusively linked to helical moiety and not to size or conformation of substituents. As chiroptical properties of these emitters are independent of substituents, this OPE scaffold can be used as basic skeleton for the design of sensing probes with high CPL efficiencies.We thank MICINN (CTQ2014-53598-R) and Junta de Andalucía (FQM1484) for financial support. Computing Center CINECA Via Magnanelli 6/3 40033 – Casalecchio di Reno (Bologna) Italy and Regione Lombardia for the LISA Grant No. “ChiPhyto: HPL13POZE1” is acknowledged for access to computational facilities. P. Reiné thanks MICINN for a FPU fellowship

Reacciones de ciclación de epoxipoliprenos catalizadas por el complejo Cp2Ticl. Aplicaciones a la síntesis de productos naturales

Univ. de Granada, Departamento de Química orgánica. Leída el 6/02/0

Prácticas de Química Orgánica-Grado Ingeniería Química

Prácticas de la asignatura Química Orgánica del Grado en Ingeniería Química

Prácticas de Materiales Ópticos. Tercer Curso del Grado de Óptica y Optometría

Compendio de prácticas de laboratorio que se realizan en la asignatura "Materiales Ópticos", del Grado en Óptica y Optometría

Tapazol deuterado y derivados, procedimiento para su preparación y usos de los mismos

Número de publicación: ES2322015 B2. Número de solicitud: 200703489.Tapazoldeuterado y derivados, procedimiento para su preparación y usos de los mismos. La invención define compuestos deuterados de fórmula (1) en la que: R{sub,1}, R{sub,2} y R{sub,3} representan de forma independiente un átomo de hidrógeno o un grupo alquilo C1-C4, opcionalmente sustituido con un grupo -OR{sub,4}, siendo R{sub,4} un átomo de hidrógeno o un grupo alquilo C1-C3 opcionalmente sustituido con fenilo; un grupo -NR{sub,5}R{sub,6}, siendo R{sub,5} y R{sub,6} de forma independiente un átomo de hidrógeno, o un grupo alquilo C1-C3, tosilo o mesilo; un grupo -SR{sub,7}, siendo R{sub,7} un átomo de hidrógeno o un grupo alquilo C1-C3; un grupo -OCOR{sub,8}, siendo R{sub,8} un grupo alquilo C1-C3 o fenilo; o un átomo de halógeno; y D representa deuterio. La invención define también un procedimiento para preparar dichos compuestos deuterados, una composición farmacéutica que los comprende, y el uso de los mismos en el campo farmacéutico y analítico.Universidad de Granad

Compuestos deuterados de 5-trideuterometil-6-metil-2-tioxo-2,3-dihidropiridin-4(1h)-ona y procedimiento de preparación de los mismos

Número de publicación: ES2352927 B1. Número de solicitud: 201001573.La invención define compuestos deuterados y también un procedimiento para preparar dichos compuestos, una composición farmacéutica que los comprende, y el uso de los mismos en el campo farmacéutico y analítico.The invention also defines a method for preparing said deuterated compounds, a pharmaceutical composition comprising said compounds and the use of said compounds in the pharmaceutical and analytical fields.Universidad de Granad