Publicaciones > Altarejos et al

Org Lett. 2021 Aug 6;23(15):6174-6178. doi: 10.1021/acs.orglett.1c02420. PubMed 34320310

Enantioselective Copper-Catalyzed Synthesis of Trifluoromethyl-Cyclopropylboronates.

Julia Altarejos¹, David Sucunza², Juan J Vaquero³, Javier Carreras¹

1. Universidad de Alcalá, Departamento de Química Orgánica y Química Inorgánica,, Alcalá de Henares 28805, Spain.  2. Instituto de Investigación Química Andrés Manuel del Río (IQAR), Universidad de Alcalá, Alcalá de Henares 28805, Spain.  3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid 28034, Spain.

Abstract

A copper-catalyzed enantioselective cyclopropanation involving trifluorodiazoethane in the presence of alkenyl boronates has been developed. This transformation enables the preparation of 2-substituted-3-(trifluoromethyl)cyclopropylboronates with high levels of stereocontrol. The products are valuable synthetic intermediates by transformation of the boronate group. This methodology can be applied to the synthesis of novel trifluoromethylated analogues of trans-2-arylcyclopropylamines, which are prevalent motifs in biologically active compounds.

Publicaciones > Garcia-Marin et al

ACS Med Chem Lett. 2021 Jul 15;12(11):1656-1662. doi: 10.1021/acsmedchemlett.1c00183. PubMed 34790291

Tripeptides as Integrin-Linked Kinase Modulating Agents Based on a Protein-Protein Interaction with α-Parvin.

Javier Garcia-Marin¹, Mercedes Griera-Merino², Alejandra Matamoros-Recio³, Sergio de Frutos⁴, Manuel Rodríguez-Puyol⁵, Ramón Alajarín¹, Juan J Vaquero⁴, Diego Rodríguez-Puyol²

1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares 28805, Spain.  2. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Ctra. Colmenar Viejo, km. 9100, Madrid 28034, Spain.  3. Instituto de Investigación Química Andrés Manuel del Río (IQAR), Universidad de Alcalá, Alcalá de Henares 28805, Spain.  4. Departamento de Biología de Sistemas, Universidad de Alcalá, Alcalá de Henares 28805, Spain.  5. Graphenano Medical Care, S.L, Yecla 30510, Spain.

Abstract

Integrin-linked kinase (ILK) has emerged as a controversial pseudokinase protein that plays a crucial role in the signaling process initiated by integrin-mediated signaling. However, ILK also exhibits a scaffolding protein function inside cells, controlling cytoskeletal dynamics, and has been related to non-neoplastic diseases such as chronic kidney disease (CKD). Although this protein always acts as a heterotrimeric complex bound to PINCH and parvin adaptor proteins, the role of parvin proteins is currently not well understood. Using in silico approaches for the design, we have generated and prepared a set of new tripeptides mimicking an α-parvin segment. These derivatives exhibit activity in phenotypic assays in an ILK-dependent manner without altering kinase activity, thus allowing the generation of new chemical probes and drug candidates with interesting ILK-modulating activities.