Kannabinoideen sintesia

Giza zeluletan azaltzen diren CB1 eta CB2 hartzaile kannabinoideekin lotura ahalbidetzen duten substantziei "Kannabinoide Sintetiko" deritze. Aipatzekoa da errezeptore hartzaileek eta kannabinoide sintetikoek antzeko egitura kimikoa dutela. Horrela, kannabinoide hauek sintetizatzeko interesa 1965. urtean hasi zen, Mechoulam eta Gaonik-k aurrera eramandako THC-ren sintesiarekin. Bide honetatik, aktibitate kannabimetikoa duten molekulen sintesia garatzen hasi zen industria farmazeutiko eta ikerketa-talde desberdinen eskutik. Gaur egun merkatuan dauden kannabinoide garrantzitsuenetarikoen sintesia azaltzea izango da lan honen helburua

Phenolic Activation in Chiral Brønsted Acid-Catalyzed Intramolecular α‑Amidoalkylation Reactions for the Synthesis of Fused Isoquinolines

An organolithium addition−intramolecular α- amidoalkylation sequence on N-phenethylimides has been developed for the synthesis of fused tetrahydroisoquinoline systems using 1,1′-bi-2-naphthol (binol)-derived Brønsted acids. This transformation is the first in which activated benzene derivatives are used as internal nucleophiles, instead of electron-rich heteroaromatics, generating a quaternary stereocenter. Phenolic substitution on the aromatic ring of the phenethylamino moiety and the use of binol-derived N-triflylphosphoramides as catalysts are determinants to achieve reasonable levels of enantioselection, that is, up to 75% enantiomeric excess, in the α-amidoalkylation step. The procedure is complementary to the intermolecular α-amidoalkylation process, as opposite enantiomers are formed, and to the Pictet− Spengler cyclization, which allows the formation of tertiary stereocentersMinisterio de Economíay Competitividad (CTQ2013-41229-P; CTQ2016-74881-P), Gobierno Vasco (IT1045-16

Chiral Bronsted Acid-Catalyzed Enantioselective alpha-Amidoalkylation Reactions: A Joint Experimental and Predictive Study,

Enamides with a free NH group have been evaluated as nucleophiles in chiral Bronsted acid-catalyzed enantioselective alpha-amidoalkylation reactions of bicyclic hydroxylactams for the generation of quaternary stereocenters. A quantitative structure-reactivity relationship (QSRR) method has been developed to find a useful tool to rationalize the enantioselectivity in this and related processes and to orient the catalyst choice. This correlative perturbation theory (PT)-QSRR approach has been used to predict the effect of the structure of the substrate, nucleophile, and catalyst, as well as the experimental conditions, on the enantioselectivity. In this way, trends to improve the experimental results could be found without engaging in a long-term empirical investigation.Ministerio de Economia y Competitividad (CTQ2013-41229-P), IKERBASQUE foundation, Gobierno Vasco (IT-623-13) and Universidad del Pais Vasco/Euskal Herriko Unibertsitatea UPV/EHU are gratefully acknowledged for their financial support. Technical and human support provided by Servicios Generales de Investigacion SGIker (UPV/EHU, MINECO, GV/EJ, ERDF and ESF) is also acknowledged

Perturbation Theory Model of Reactivity and Enantioselectivity of Palladium-catalyzed Heck-Heck cascade reactions

Enantioselective intramolecular Heck-Heck cascade reactions have emerged as an excellent tool for the construction of polycyclic frameworks, such as Lycorane alkaloids, Xestoquinone and analogues. However, it is particularly difficult to rationalize the effect of simultaneous changes in both the structure of many molecular entities and experimental conditions (temperature, time, solvent, ligand, catalyst loading, etc.) on reactivity and enantioselectivity. In this work, a computational model to predict the enantiomeric excess and the yield of Heck-Heck cascade reactions has been developed. The model combines Perturbation Theory (PT) and Quantitative Structure-Reactivity Relationships (QSRR) ideas for the prediction of two different outputs with the same equation (% ee and % yield). This model predicted 520 experimental outcomes with a correlation coefficient R = 0.89, standard error of estimates SEE = 1.19 %, and a cross-validation correlation coefficient q2 = 0.79. The use of the model has been illustrated with a case of study, the Heck-Heck cascade reaction of a 2,3-dialkenyl pyrrole using Pd(dba)2 and (R)-BINAP. For the first time, a 2000-points simulation in a ternary phase diagrams shows the effect of the concentration of the catalyst, the base, and ligand on the enantioselectivity of this reaction. The QSRR model also predicts trends in structural outcomes, such halides vs. triflates, or the ligand structure. Therefore, the model opens the door to the design of new chiral ligands and helps to find trends to improve the experimental results in enantioselective polyene cyclisationsMinisterio de Economía y Competitividad (CTQ2013-41229-P), Gobierno Vasco (IT-623-13

Kannabinoideen sintesia

Giza zeluletan azaltzen diren CB1 eta CB2 hartzaile kannabinoideekin lotura ahalbidetzen duten substantziei "Kannabinoide Sintetiko" deritze. Aipatzekoa da errezeptore hartzaileek eta kannabinoide sintetikoek antzeko egitura kimikoa dutela. Horrela, kannabinoide hauek sintetizatzeko interesa 1965. urtean hasi zen, Mechoulam eta Gaonik-k aurrera eramandako THC-ren sintesiarekin. Bide honetatik, aktibitate kannabimetikoa duten molekulen sintesia garatzen hasi zen industria farmazeutiko eta ikerketa-talde desberdinen eskutik. Gaur egun merkatuan dauden kannabinoide garrantzitsuenetarikoen sintesia azaltzea izango da lan honen helburua