RESUMO
Cu-catalyzed asymmetric allylic borylation of 3,3'-disubstituted 1-vinylcyclobutan-1-ols renders axially chiral allylborane systems, with high asymmetric induction for both enantiomers, by precise selection of the cis or trans substrate. The enantioenriched alkylidenecyclobutanes served as chiral platform to prove the conceptually challenging transference of the axial-to-point chirality through two new stereocenters and one pseudoasymmetric carbon generated via diastereoconvergent allylation of aldehydes, without enantioselective erosion.
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The rich reactivity profile of cyclopropanes has been extensively explored to trigger new organic transformations that enable unusual disconnective approaches to synthesize molecular motifs that are not easily reached through conventional reactions. In particular, the chemistry of cyclopropanes has received special attention in the last decade, with multiple new approaches that capitalize on the use of organocatalysis for the activation of the cyclopropane scaffold. This situation has also opened the possibility of developing enantioselective variants of many reactions that until now were only carried out in an enantiospecific or diastereoselective manner. Our group has been particularly active in this field, focusing more specifically on the use of aminocatalysis and Brønsted acid catalysis as major organocatalytic activation manifolds to trigger new unprecedented transformations involving cyclopropanes that add to the current toolbox of general methodologies available to organic chemists for the enantioselective synthesis of chiral compounds.
Assuntos
Metionina , Sinais Direcionadores de Proteínas , Humanos , Alelos , Racemetionina , Antígenos HLA-B/genéticaRESUMO
Sequence and expression analysis of the HLA-DRB1*10:38 allele.
Assuntos
Cadeias HLA-DRB1 , Humanos , Cadeias HLA-DRB1/genética , Sequência de Bases , AlelosRESUMO
An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19's pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.
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The contribution to the energy barrier of a series of tethers in transannular cycloadditions of cycloalkenes with hydrazones has been computationally studied by using DFT. The Houk's distortion model has been employed to evaluate the influence of the tether in the cycloaddition reaction. That model has been extended to determine the contribution of each tether and, more importantly, the effect exerted between them. In addition to the distortion induced by the tethers, the entropy effects caused by them has also been studied. The analysis of the evolution of the electron localization function along the reaction revealed the highly concerted character of the reaction.
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We have demonstrated that the catalytic and enantioselective vinylcyclopropane-cyclopentene rearrangement can be carried out on (vinylcyclopropyl)acetaldehydes through activation via enamine intermediates. The reaction makes use of racemic starting materials that, upon ring opening facilitated by the catalytic generation of a donor-acceptor cyclopropane, deliver an acyclic iminium ion/dienolate intermediate in which all stereochemical information has been deleted. The final cyclization step forms the rearrangement product, showing that chirality transfer from the catalyst to the final compound is highly effective and leads to the stereocontrolled formation of a variety of structurally different cyclopentenes.
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Characterization of six novel HLA alleles by next-generation sequencing.
Assuntos
Antígenos HLA-A , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Antígenos HLA-A/genética , Cadeias HLA-DRB1/genéticaRESUMO
Genomic full-length characterization of the HLA-DQB1*03:25:01 allele.
Assuntos
Antígenos HLA-DQ , Humanos , Antígenos HLA-DQ/genética , Alelos , Cadeias beta de HLA-DQ/genética , HaplótiposRESUMO
Background: The aim of this study was to evaluate the long-term outcome of our series of narcolepsy type 1 (NT1) patients with comorbid autoimmune diseases (ADs) and other immunopathological diseases (IDs), focusing on the incidence of new ADs and IDs in this sample. Methods: A longitudinal observational study was conducted over 6 years (2014 - 2020) in a series of 158 Caucasians NT1 patients (96 males; mean age: 50.1 ± 19.0 years) from the previous study. All but one case (familial case) were HLA-DQB1*06:02-positive. The diagnosis of narcolepsy was made according to the International Classification of Sleep Disorders (ICSD-3). Results: Twenty-one patients have been diagnosed with a new ID, 10 of them with an AD (autoimmune thyroid disease, psoriasis, rheumatoid arthritis, transverse myelitis, granuloma annulare, primary biliary cirrhosis, alopecia areata and antiphospholipid syndrome), and 11 with other IDs (allergic rhinitis, allergic asthma, atopic dermatitis, food allergy, contact dermatitis and drug allergy). One patient was diagnosed with two new ADs. We found IDs in 46 patients (24 females and 22 males) and the overall prevalence in this series is actually 29.11%; 22 of them (13.92%) had an AD, with a percentage higher than estimated in the general population. Conclusions: The prevalence of AD/ID is high in our series, suggesting that NT1 might arise on a background of generalized susceptibility to immune-mediated processes. The occurrence of an ID can in turn influence the development of others in genetically predisposed individuals, which explains the increased associations observed in this long-term study.
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We have studied the enantioselective transannular aminohalogenation reaction of unsaturated medium-sized cyclic benzosulfonamides by using both chiral Brønsted acid and phase-transfer catalysis. Under optimized conditions, a variety of bicyclic adducts can be obtained with good yields and high enantioselectivities. The mechanism of the reaction was also studied by using computational tools; we observed that the reaction involves the participation of a conformer of the nine-membered cyclic substrate with planar chirality in which the stereochemical outcome is controlled by the relative reactivity of the two pseudorotational enantiomers when interacting with the chiral catalyst.
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Ácidos , Estereoisomerismo , CatáliseRESUMO
The Prins reaction is a very convenient synthetic platform for the preparation of oxygen-containing heterocyclic compounds, especially tetrahydropyrans and tetrahydrofurans. While this reaction has been extensively used by synthetic chemists since its discovery, the last years have witnessed impressive improvements in its performance and scope and especially in the development of new catalytic and enantioselective versions. This mini-review presents these recent advances through selected representative examples.
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Characterization of two novel HLA class I null alleles.
Assuntos
Antígenos HLA-B , Nucleotídeos , Humanos , Alelos , Mutação , Antígenos HLA-B/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
A transannular approach has been developed for the construction of pyrrolo[1,2-b]isoquinolinones starting from benzo-fused nine-membered enelactams. This process takes place in the presence of a halogenating agent and under Brønsted acid catalysis and proceeds via a transannular amidohalogenation, followed by elimination. The reaction has been found to be wide in scope, enabling the formation of a variety of tricyclic products in good overall yield, regardless of the substitution pattern in the initial lactam substrate. The reaction has also been applied to the total synthesis of a reported topoisomerase I inhibitor and to the formal synthesis of rosettacin. Further extension of this methodology allows the preparation of 10-iodopyrrolo[1,2-b]isoquinolinones by using an excess of halogenating agent and these compounds can be further manipulated through standard Suzuki coupling chemistry into a variety of 10-aryl-substituted pyrrolo[1,2-b]isoquinolinones.
Assuntos
CatáliseRESUMO
The novel HLA-DQB1*04:02:01:16Q allele showing a point mutation in the intron 3.
Assuntos
Mutação Puntual , Alelos , Cadeias beta de HLA-DQ/genética , Humanos , ÍntronsRESUMO
HLA-C*08:243 differs from C*08:51 by a single nucleotide substitution in codon 156 (G > T).
Assuntos
Medula Óssea , Antígenos HLA-C , Alelos , Éxons/genética , Antígenos HLA-C/genética , Humanos , Análise de Sequência de DNA , Doadores de TecidosRESUMO
A palladium-catalyzed asymmeric conjugate addition of aryl boronic acids to medium-sized cycloalkenones followed by intramolecular aldol trapping is reported. The use of in situ formed [Pd/(QuinoxP*)] as the catalyst enables the synthesis of arylbicyclic scaffolds in good yields and with excellent stereocontrol (up to 7 : 1 dr, up to 99% ee). The reaction is applicable to a range of medium size ketoenone substrates and funcionalized aryl boronic acids, including heterocyclic compounds.