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

Intramolecular Addition of Heteroaryllithiums onto Activated Alkenes. Access to Heterofused Indolizines and Pyrroloazepines

Heteroaryllithiums, obtained via MesLi mediated halogen- lithium exchange, undergo intramolecular addition onto acrylamide and acrylate moieties. Both electron rich (thiophenyl) and electron deficient (pyridinyl, quinolinyl) heteroaromatic halides can be used for the formation of six- and seven membered rings, providing an efficient route to fused indolizines and pyrroloazepines in moderate to good yields.Ministerio de Economía y Competitividad (CTQ2013-41229-P, CTQ2016-74881-P), Gobierno Vasco (IT1045-16

Generation of Tertiary and Quaternary Stereocenters via Palladium-Catalyzed Intramolecular Heck-type Reactions for the Stereocontrolled Synthesis of Pyrrolo[1,2-b]isoquinolines

The generation of quaternary and tertiary stereocenters on C-10 of the pyrroloisoquinoline skeleton through intramolecular Mizoroki-Heck reactions of 2-alkenyl substituted pyrroles and pyrrolidines has been studied. The cyclizations proceeded with moderate to good yields (up to 81%), although with low enantioselection when chiral phosphanes, such as (R)-BINAP, are used as ligands. However, enantiomerically pure 10-substituted pyrrolo[1,2-b]isoquinolines have been efficiently obtained through a diastereoselective approach using chiral non-racemic pyrrolidines as substrates, generating a tertiary stereocenterMinisterio de Economía y Competitividad (CTQ2013-41229-P), Gobierno Vasco (IT-623-13), Universidad del País Vasco / Euskal Herriko Unibertsitatea UPV/EHU (UFI11/22, PPM12/03

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