Free-Radical Deoxygenative Amination of Alcohols via Copper Metallaphotoredox Catalysis.

Alcohols are among the most abundant chemical feedstocks, yet they remain vastly underutilized as coupling partners in transition metal catalysis. Herein, we describe a copper metallaphotoredox manifold for the open shell deoxygenative coupling of alcohols with -nucleophiles to forge C()-N bonds, a linkage of high value in pharmaceutical agents that is challenging to access via conventional cross-coupling techniques. -heterocyclic carbene (NHC)-mediated conversion of alcohols into the corresponding alkyl radicals followed by copper-catalyzed C-N coupling renders this platform successful for a broad range of structurally unbiased alcohols and 18 classes of -nucleophiles.

Room-Temperature Cu-Catalyzed Amination of Aryl Bromides Enabled by DFT-Guided Ligand Design.

Ullmann-type C-N coupling reactions represent an important alternative to well-established Pd-catalyzed approaches due to the differing reactivity and the lower cost of Cu. While the design of anionic Cu ligands, particularly those by Ma, has enabled the coupling of various classes of aryl halides and alkyl amines, most methods require conditions that can limit their utility on complex substrates. Herein, we disclose the development of anionic ,-diarylbenzene-1,2-diamine ligands that promote the Cu-catalyzed amination of aryl bromides under mild conditions.

Iridium-Catalyzed Asymmetric Hydrogenation of 2,3-Diarylallyl Amines with a Threonine-Derived P-Stereogenic Ligand for the Synthesis of Tetrahydroquinolines and Tetrahydroisoquinolines.

Chiral compounds containing nitrogen heteroatoms are fundamental substances for the chemical, pharmaceutical and agrochemical industries. However, the preparation of some of these interesting scaffolds is still underdeveloped. Herein we present the synthesis of a family of P-stereogenic phosphinooxazoline iridium catalysts from L-threonine methyl ester and their use in the asymmetric hydrogenation of N-Boc-2,3-diarylallyl amines, achieving very high enantioselectivity.

Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation.

Chiral amines are key structural motifs present in a wide variety of natural products, drugs, and other biologically active compounds. During the past decade, significant advances have been made with respect to the enantioselective synthesis of chiral amines, many of them based on catalytic asymmetric hydrogenation (AH). The present review covers the use of AH in the synthesis of chiral amines bearing a stereogenic center either in the α, β, or γ position with respect to the nitrogen atom, reported from 2010 to 2020.

A General -alkylation Platform via Copper Metallaphotoredox and Silyl Radical Activation of Alkyl Halides.

The catalytic union of amides, sulfonamides, anilines, imines or -heterocycles with a broad spectrum of electronically and sterically diverse alkyl bromides has been achieved via a visible light-induced metallaphotoredox platform. The use of a halogen abstraction-radical capture (HARC) mechanism allows for room temperature coupling of C( )-bromides using simple Cu(II) salts, effectively bypassing the prohibitively high barriers typically associated with thermally-induced S2 or S1 -alkylation. This regio- and chemoselective protocol is compatible with >10 classes of medicinally-relevant -nucleophiles, including established pharmaceutical agents, in addition to structurally diverse primary, secondary and tertiary alkyl bromides.

P-Stereogenic Amino-Phosphines as Chiral Ligands: From Privileged Intermediates to Asymmetric Catalysis.

Among chiral phosphines, P-stereogenic phosphines provide unparalleled activity and selectivity and have thus emerged as "state-of-the-art" ligands for asymmetric hydrogenation and other industrially relevant processes. However, the synthesis of this type of ligand implies lengthy multistep sequences, which are a hurdle for many laboratories. There is a lack of methods for the rapid construction of P-stereogenic phosphine ligands.

Catalytic Regioselective Isomerization of 2,2-Disubstituted Oxetanes to Homoallylic Alcohols.

The selective isomerization of strained heterocyclic compounds is an important tool in organic synthesis. An unprecedented regioselective isomerization of 2,2-disubstituted oxetanes into homoallylic alcohols is described. The use of tris(pentafluorophenyl)borane (B(C F ) ) a commercially available Lewis acid was key to obtaining good yields and selectivities since other Lewis acids afforded mixtures of isomers and substantial polymerization.

Highly Enantioselective Iridium-Catalyzed Hydrogenation of 2-Aryl Allyl Phthalimides.

The iridium-catalyzed asymmetric hydrogenation of 2-aryl allyl phthalimides to afford enantioenriched β-aryl-β-methyl amines is presented. Recently developed Ir-MaxPHOX catalysts are used for this enantioselective transformation. The mild reaction conditions and the feasible removal of the phthalimido group makes this catalytic method easily scalable and of great interest to afford chiral amines.

Iridium-Catalyzed Isomerization of N-Sulfonyl Aziridines to Allyl Amines.

The Crabtree's reagent catalyzes the isomerization of N-sulfonyl 2,2-disubstituted aziridines to allyl amines. The selectivity of allyl amine vs imine is very high (up to 99/1). The unprecedented isomerization takes place in mild conditions without activation of the catalyst by hydrogen.

Total Synthesis of ( R)-Sarkomycin Methyl Ester via Regioselective Intermolecular Pauson-Khand Reaction and Iridium-Catalyzed Asymmetric Isomerization.

A new five-step enantioselective synthesis of ( R)-sarkomycin methyl ester is described. The cyclopentane scaffold was built by a regioselective intermolecular Pauson-Khand reaction. Enantioselectivity was introduced by a novel Ir-catalyzed isomerization reaction.

[Long-term effects of continuous positive airway pressure treatment on subclinical atherosclerosis in obstructive sleep apnoea syndrome].

Background And Objective: Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease. Our objective was to evaluate subclinical atherosclerosis in OSA patients and the effect of continuous positive airway pressure (CPAP) treatment on carotid intima-media thickness (cIMT).

Patients And Method: We included 125 patients with suspected OSA.

[Intraabdominal fat redistribution in long-term continuous positive airway pressure treatment in obstructive sleep apnea patients].

Background And Objective: Obesity is the main risk factor for obstructive sleep apnoea (OSA). The aim was to evaluate the long-term effect of continuous positive airway pressure (CPAP) on intraabdominal fat distribution in OSA patients.

Patients And Methods: Fifty OSA patients with and 35 without CPAP treatment criteria were followed-up for 2 years.

Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders.

Background: PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis.

FABP4 plasma concentrations are determined by acquired metabolic derangements rather than genetic determinants.

Background And Aims: Circulating FABP4 is strongly associated with metabolic and cardiovascular risk (CVR) and has been proposed as a new risk biomarker. Several FABP4 gene polymorphisms have been associated with protein expression in vitro and metabolic and vascular alterations in vivo. The aim of this study is to evaluate the impact of FABP4 polymorphisms on FABP4 plasma levels and subclinical arteriosclerosis in patients with obesity, metabolic syndrome (MS) or type 2 diabetes (T2DM).

Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess.

Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1.

Terrestrial and marine perspectives on modeling organic matter degradation pathways.

Organic matter (OM) plays a major role in both terrestrial and oceanic biogeochemical cycles. The amount of carbon stored in these systems is far greater than that of carbon dioxide (CO2 ) in the atmosphere, and annual fluxes of CO2 from these pools to the atmosphere exceed those from fossil fuel combustion. Understanding the processes that determine the fate of detrital material is important for predicting the effects that climate change will have on feedbacks to the global carbon cycle.

Circulating PCSK9 levels are positively correlated with NMR-assessed atherogenic dyslipidaemia in patients with high cardiovascular risk.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene regulates cholesterol homoeostasis by accelerating low-density lipoprotein receptor (LDLR) degradation resulting in the decreased catabolism of low-density lipoprotein (LDL) leading to hypercholesterolaemia. PCSK9 has also been related to other metabolic risk factors such as triglycerides (TGs) and glucose levels and body mass index (BMI). Therefore, our aim was to study the relationship between the PCSK9 and the lipid and lipoprotein profile.

Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients.

HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted.

Physical activity below the minimum international recommendations improves oxidative stress, ADMA levels, resting heart rate and small artery endothelial function.

Background: A moderate level of physical activity (PA), such as a daily 30-min walk, reduces cardiovascular risk. There is a lack of evidence about the cardiovascular benefits of PA below this recommendation of minimum PA level.

Objective: We aimed to study the impact of a lower level of PA on cardiovascular health.

[Interaction of FABP4 with plasma membrane proteins of endothelial cells].

Introduction: Fatty acid binding protein (FABP4) is an adipose tissue-secreted adipokine implicated in the regulation of the energetic metabolism and inflammation. High levels of circulating FABP4 have been described in people with obesity, atherogenic dyslipidemia, diabetes and metabolic syndrome. Recent studies have demonstrated that FABP4 could have a direct effect on peripheral tissues and, specifically, on vascular function.

Prevalence of atherogenic dyslipidemia in primary care patients at moderate-very high risk of cardiovascular disease. Cardiovascular risk perception.

Introduction: Atherogenic dyslipidemia is an important risk factor for cardiovascular disease. We aim to determine atherogenic dyslipidemia prevalence in primary care patients at moderate-very high cardiovascular risk and its associated cardiovascular risk perception in Spain.

Methods: This cross-sectional study included 1137 primary care patients.

Subclinical atherosclerosis determinants in morbid obesity.

Background And Aims: Obesity is associated with increased cardiovascular risk. However, the impact of morbid obesity on vascular structure and function is not well understood. This study was designed to appraise subclinical atherosclerosis markers, including carotid intima media thickness (cIMT), endothelial function, and arterial wall stiffness, and their determinants, in morbidly obese patients.

Circulating FABP4 is a marker of metabolic and cardiovascular risk in SLE patients.

The aim of this study is to determine if circulating fatty acid-binding protein 4 (FABP4) plasma levels are a possible marker of metabolic risk in SLE patients. Circulating levels of adipose FABP4 are associated with adiposity, insulin resistance (IR), metabolic syndrome, diabetes and cardiovascular diseases. Patients affected by systemic lupus erythematosus (SLE) show an accelerated atherosclerosis that cannot be entirely explained by traditional cardiovascular risk factors.

Circulating FABP4 and FABP5 levels are differently linked to OSA severity and treatment.

Objective: To evaluate circulating adipocyte and epidermal fatty acid-binding protein (FABP4 and FABP5) concentrations in patients with obstructive sleep apnea (OSA), as well as the effects of continuous positive airway pressure (CPAP) treatment.

Methods: Our cross-sectional study included 125 patients. After polysomnography, 58 participants met the criteria for CPAP treatment and were included in a closed cohort study of 8 weeks of CPAP treatment.