Site-selective oxidative dearomatization of phenols and naphthols into ortho-quinols or epoxy ortho-quinols using oxone as the source of dimethyldioxirane

"This is the peer reviewed version of the following article: Advanced Synthesis and Catalysis 361.19 (2019): 4468-4473, which has been published in final form at https://doi.org/10.1002/adsc.201900660. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions"A novel reactivity of dimethyldioxirane, generated in situ from Oxone and acetone, with substituted phenols and naphthols is reported. This methodology allowed the synthesis of ortho-quinols or epoxy ortho-quinols from a site-selective oxidative dearomatization process, with good yields under very mild conditions. A short total synthesis of natural product lacinilene C methyl ether is also described using this process as the key stepThe authors thank Ministerio de Economía y Competitividad (Grant CTQ2017-83309-P) for financial suppor

Selective Oxidative Dearomatization of Angular Tetracyclic Phenols by Controlled Irradiation under Air: Synthesis of an Angucyclinone-Type Double Peroxide with Anticancer Properties

Angular tetracyclic p-peroxyquinols, p-quinols and a pentacyclic double peroxide, showing anticancer properties, were Selective oxidative dearomatization of angular tetracyclic phenols by controlled irradiation under air: synthesis of an angucyclinone‐type double peroxide with anticancer properties María J. Cabrera-Afonso,a Silvia R. Lucena,b Ángeles Juarranz,b Antonio Urbano,*a,c M. Carmen Carreño*a,c aDepartamento de Química Orgánica, Universidad Autónoma de Madrid (UAM), Cantoblanco, 28049-Madrid, Spain. bDepartamento de Biología, UAM, Cantoblanco, 28049-Madrid, Spain. cInstitute for Advanced Research in Chemical Sciences (IAdChem), UAM, Cantoblanco, 28049-Madrid, Spain. Supporting Information Placeholder synthesized from the corresponding phenols by an environmentally friendly solvent- and wavelength-controlled irradiation under air in the absence of an external photosensitizerWe thank MINECO (Grants CTQ2017-83309-P, CTQ2014-53894R and FIS PI15/00974) for financial suppor

Isonitriles as Alkyl Radical Precursors in Visible Light Mediated Hydro- and Deuterodeamination Reactions

Herein, we report the use of isonitriles as alkyl radical precursors in light-mediated hydro- and deuterodeamination reactions. The reaction is scalable, shows broad functional group compatibility and potential to be used in late-stage functionalization. Importantly, the method is general for Cα-primary, Cα-secondary and Cαtertiary alkyl isonitriles. For most examples, high yields were obtained through direct visible-light irradiation of the isonitrile in the presence of a silyl radical precursor. Interestingly, in the presence of an organic photocatalyst (4CzIPN) a dramatic acceleration was observed. Indepth mechanistic studies using UV/Vis absorption, steady-state and time-resolved photoluminescence, and transient absorption spectroscopy suggest that the excited state of 4CzIPN can engage in a single-electron transfer with the isonitrileWe thank the European Research Council (ERC CoG 101002715 SCAN) and Spanish MCIN/AEI/10.13039/ 501100011033 (grant n° PID2019-107380GB-I00 and PID2022-142594NB-I00 to MT, PID2022-141688OB-I00 and PID2020-118593RB-C22 to ML, PID2019-106184GB-I00, PID2022-139318NB I00 and RED2022-134287-T to IF) for financial support. I.Q. and L.N. thank Comunidad de Madrid for a predoctoral fellowship, and M.M. acknowledges Ministerio de Universidades for a FPU fellowship (FPU20/06

Metal-free visible light-promoted synthesis of isothiazoles: a catalytic approach for N-S bond formation from iminyl radicals under batch and flow conditions

A sustainable synthesis of isothiazoles has been developed using an α-amino-oxy acid auxiliary and applying photoredox catalysis. This simple strategy features mild conditions, broad scope and wide functional group tolerance representing a new enviromentally friendly option to prepare these highly valuable heterocycles. Furthermore, the synthetic value of the method is highlighted by the preparation of a natural product derivative and the implementation of the reaction in a continuous flow setupWe acknowledge the financial support by the Spanish Government (RTI2018-095038-B-I00) and ERC (ERC-CG, 647550

Oxidative dearomatization of phenols by Oxone® or aerobicphotooxidation

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 29-10-2018Esta tesis tiene embargado el acceso al texto completo hasta el 29-04-2020Este trabajo ha sido realizado en el Departamento de Química Orgánica de la Universidad Autónoma de Madrid bajo la dirección de la Dra. Mª del Carmen Carreño y el Dr. Antonio Urbano Pujol. El trabajo se ha llevado a cabo gracias a la financiación del Ministerio de Ciencia e Innovación (Proyectos referencias: CTQ2011-24783/BQU, CTQ2014-53894-R y CTQ2017-83309-P) y a la obtención de una Beca de Formación para Personal Investigador (FPI-2014) de la Universidad Autónoma de Madrid. Durante el tiempo de realización de esta tesis doctoral se ha realizado una estancia de 3 meses en la Universidad de Pensilvania, Filadelfia bajo la dirección del Prof. Gary A. Molander al cual quiero agradecer la oportunidad de haber colaborado en su grupo de investigació

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old