Abstract. Nowadays, the development of new enantioselective processes is highly relevant in chemistry due to the relevance of chiral compounds in biomedicine (mainly drugs) and in other fields, such as agrochemistry, animal feed, and flavorings. Among them, organocatalytic methods have become an efficient and sustainable alternative since List and MacMillan pioneering contributions were published in 2000. These works established the term asymmetric organocatalysis to label this area of research, which has grown exponentially over the last two decades. Since then, the scientific community has attended to the discovery of a plethora of organic reactions and transformations carried out with excellent results in terms of both reactivity and enantioselectivity. Looking back to earlier times, we can find in the literature a few examples where small organic molecules and some natural products could act as effective catalysts. However, with the birth of this type of catalysis, new chemical architectures based on amines, thioureas, squaramides, cinchona alkaloids, quaternary ammonium salts, carbenes, guanidines and phosphoric acids, among many others, have been developed. These organocatalysts have provided a broad range of activation modes that allow privileged interactions between catalysts and substrates for the preparation of compounds with high added value in an enantioselective way. Here, we briefly cover the history of this chemistry, from our point of view, including our beginnings, how the field has evolved during these years of research, and the road ahead.
Abstract. Funapide is a 3,3’-spirocyclic oxindole with promising analgesic activity. A reported pilot-plant scale synthesis of this chiral compound involves an asymmetric aldol reaction, catalyzed by a common bifunctional thiourea structure. In this work, we show that the swapping of the thiourea unit of the catalyst for a tailored squaramide group provides an equally active, but rewardingly more selective, catalyst for this aldol reaction (from 70.5 to 85 % ee). The reaction was studied first on a model oxindole compound. Then, the set of optimal conditions was applied to the target funapide intermediate. The applicability of these conditions seems limited to oxindoles bearing the 3-substituent of funapide. Exemplifying the characteristics of target-focused methodological development, this study highlights how a wide-range screening of catalysts and reaction conditions can provide non-negligible improvements in an industrially viable asymmetric transformation.
Our group has just received an accesit of Prizes “Tercer Milenio” in the category of Research and Future for our work in organoasymmetric catalysis oriented to industrial applications. Last Thursday, together with the other 14 awarded projects and careers, Raquel picked the prize up from Guillermo Ríos, head of Avanza during the ceremony celebrated in the Rectorate of the University of Zaragoza. We are very happy!!!
Abstract. In this work, two thiourea ligands bearing a phosphine group in one arm and in the other a phenyl group (T2) or 3,5-di-CF3 substituted phenyl ring (T1) have been prepared and their coordination to Au and Ag has been studied. A different behavior is observed for gold complexes, a linear geometry with coordination only to the phosphorus atom or an equilibrium between the linear and three-coordinated species is present, whereas for silver complexes the coordination of the ligand as P^S chelate is found. The thiourea ligands and their complexes were explored against different cancer cell lines (HeLa, A549, and Jurkat). The thiourea ligands do not exhibit relevant cytotoxicity in the tested cell lines and the coordination of a metal triggers excellent cytotoxic values in all cases. In general, data showed that gold complexes are more cytotoxic than the silver compounds with T1, in particular the complexes [AuT1(PPh3)]OTf, the bis(thiourea) [Au(T1)2]OTf and the gold-thiolate species [Au(SR)T1]. In contrast, with T2 better results are obtained with silver species [AgT1(PPh3)]OTf and the [Ag(T1)2]OTf. The role played by the ancillary ligand bound to the metal is important since it strongly affects the cytotoxic activity, being the bis(thiourea) complex the most active species. This study demonstrates that metal complexes derived from thiourea can be biologically active and these compounds are promising leads for further development as potential anticancer agents.
Keywords: biological properties; cancer; cytotoxicity; gold; metal complexes; silver; thiourea
CSIC organices this week an interesting event dedicated to children from schools of Aragon and surprise them with Science (“Semana de la Ciencia”). Sandra, Christian, Guillermo and Fanny from HOCA lab, have been awakening scientific vocations. Maybe some of them will incorporated to our Institute, the ISQCH, in the near future 😉
Last Tuesday, Sandra Ardevines, PhD student in our group, gave her talk about the “Synthesis of 1,4-dihydropyridine derivatives and the study of their biological properties” during the first session of the IV NanoOncology Workshop (October, 19-20th) celebrated in Zaragoza. Well done!!
Miryam Garcés Marín. “Searching for more sustainable and effective methods for the synthesis of chiral chromenes of biological importance” Supervisors: Dr. Eugenia Marqués-López and Dr. Raquel P. Herrera.
Juan Carlos Pérez Sánchez. “Synthesis and study of new metal-organocatalysts for dual catalysis” Supervisors: Dr. Raquel P. Herrera and Prof. M. Concepción Gimeno.
Sandra Ardevines Asín. “Organocatalytic reactions for the synthesis of intermediates of biological interest” Supervisors: Dr. Eugenia Marqués-López and Dr. Raquel P. Herrera.
Christian Ascaso Alegre. “Chemoenzymatic cascades for the generation of new C-C bonds” Supervisors: Dr. Juan Mangas-Sánchez and Dr. Raquel P. Herrera.
Guillermo Canudo Barreras. “Synthesis of heterocycles through gold catalysis” Supervisors: Dr. Raquel P. Herrera and Prof. M. Concepción Gimeno.
Alberto Eizaguerri Serrano. “Application of organo- and bio- catalytic strategies for the preparation of products of industrial interest” Supervisors: Dr. Juan Mangas-Sánchez and Dr. Raquel P. Herrera.
Inés Sebastián Molia. “Synthesis of gold(I) and gold(III) models of metalloenzymes: Catalytic and therapeutic properties” Supervisors: Dr. Juan Mangas Sánchez and Prof. M. Concepción Gimeno.
Abstract. Two new organic–inorganic salts of perhalidometallates with protonated organic amine cations have been synthesized and characterized by X-ray diffraction and thermal analysis. (CHBMAH2)ZnBr4·3/2H2O 1 and (CHBMAH2)ZnCl44 [(CHBMAH2)2+: 1,3-cyclohexanebis(methylammonium)] were obtained in single-crystal form. The crystal packing in all of the obtained compounds is governed by the formation of various non-covalent intermolecular forces between tetrahalidometallate anions and organic cations, assisted by water molecules in the hydrates. Hirshfeld surface analysis denotes that the most important contributions to the crystal packing are X···H/H···X (X: Cl, Br, I) and H···H interactions. Interestingly, the compound 1,3-cyclohexanebis(methylammonium)tetrachloridozincate (II) dihydrate, (CHBMAH2)ZnCl4·2H2O 2, undergoes thermally-triggered single-crystal-to-single-crystal (SCSC) transformation upon dehydration to produce a supramolecular solid compound, 1,3-cyclohexanebis(methylammonium) tetrachloridozincate (II), (CHBMAH2)ZnCl44. The SCSC transformation causes changes in the lattice parameters and a structural rearrangement. Furthermore, the catalytic properties of (CHBMAH2)ZnCl4·2H2O 2 and (CHBMAH2)CdI4·2H2O 3 have been explored in the acetalization process using various uncommon alcohols, beyond methanol or ethanol, for the first time in the literature, with outstanding results, and opening the door to the formation of alternative acetals.