Impact of Frailty on Outcomes After Transcatheter Edge-to-Edge Repair With MitraClip (from the National Inpatient Sample Database).

Transcatheter edge-to-edge repair (TEER) with MitraClip (Abbott, Santa Clara, California) is a frequently chosen method for mitral valve repair for patients at high surgical risk. We investigated the impact of frailty on outcomes of patients who underwent TEER. We reviewed the National Inpatient Sample to identify patients that underwent TEER with MitraClip. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. The primary end point was in-hospital mortality. The secondary end points included blood transfusion, respiratory failure, sepsis, length of stay, and total hospitalization cost. Univariate and multivariate logistic regression analyses were performed to determine any association between frailty and primary or secondary outcomes. From January 2016 to December 2017, 10,055 patients underwent TEER in the United States, and 10.6% of them met the criteria for frailty. The frail group showed increased in-hospital mortality (7.04% vs 1.61%, p <0.001) and respiratory failure (3.75% vs 0.95%, p <0.001). Similarly, the frail group had longer lengths of stay (6 vs 2 days, p <0.001) and higher hospitalization costs ($224.8k vs $180.9k, p <0.001). After multivariable logistic regression analysis, frailty was associated with increased in-hospital mortality (odds ratio [OR] 3.70, 95% confidence interval [CI] 1.91 to 7.18, p <0.001), transfusion (OR 1.85, 95% CI 1.07 to 3.19, p = 0.029), respiratory failure (OR 3.56, 95% CI 1.48 to 8.52, p = 0.005), and sepsis (OR 4.17, 95% CI 1.84 to 9.46, p = 0.001). In conclusion, frailty was present in about 10% of patients who underwent TEER from 2016 to 2017. The presence of frailty was associated with worse in-hospital outcomes and greater resource use.

Copper Catalyzed Regioselective and Stereospecific Aziridine Opening with Pyridyl Grignard Nucleophiles.

Copper catalyzed regioselective and stereospecific coupling between aziridines and in situ generated pyridine Grignard reagents is reported. This method provides ß-pyridylethylamines with diverse structures and functionalities from aziridines and iodopyridines. ß-Pyridylethylamines are potential scaffolds for the synthesis of biologically active compounds often found in pharmaceuticals. The synthesis of challenging chiral dihydroazaindoles was also achieved through mild one-pot reaction conditions via aziridine opening followed by nucleophilic cyclization.

Cu-Catalyzed Asymmetric Aminoboration of E-Vinylarenes with pivZPhos as the Ligand.

A Cu-catalyzed enantioselective aminoboration of E-vinylarenes with pivZPhos as a ligand is reported. Enantioenriched aminoborates are prepared with excellent regio- and enantioselectivities up to >99:1 er under the optimized conditions. The utility of the current method was further established by rapid conversion of an adduct to a chiral benzo[f][1,4]oxazepine. A model for the stereochemistry of the asymmetric aminoboration process, which agrees with the experimental outcomes, was generated by computational analysis of the systems.

Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B.

(+)-Psiguadial B is a diformyl phloroglucinol meroterpenoid that exhibits antiproliferative activity against the HepG2 human hepatoma cancer cell line. This full account details the evolution of a strategy that culminated in the first enantioselective total synthesis of (+)-psiguadial B. A key feature of the synthesis is the construction of the trans-cyclobutane motif by a Wolff rearrangement with in situ catalytic, asymmetric trapping of the ketene. An investigation of the substrate scope of this method to prepare enantioenriched 8-aminoquinolinamides is disclosed. Three routes toward (+)-psiguadial B were evaluated that featured the following key steps: (1) an ortho-quinone methide hetero-Diels-Alder cycloaddition to prepare the chroman framework, (2) a Prins cyclization to form the bridging bicyclo[4.3.1]decane system, and (3) a modified Norrish-Yang cyclization to generate the chroman. Ultimately, the successful strategy employed a ring-closing metathesis to form the seven-membered ring and an intramolecular O-arylation reaction to complete the polycyclic framework of the natural product.

New bio-based monomers: tuneable polyester properties using branched diols from biomass.

A family of monomers, including 2,5-hexandiol, 2,7-octandiol, 2,5-furandicarboxylic acid (FDCA), terephthalic acid (TA), and branched-chain adipic and pimelic acid derivatives, all find a common derivation in the biomass-derived platform molecule 5-(chloromethyl)furfural (CMF). The diol monomers, previously little known to polymer chemistry, have been combined with FDCA and TA derivatives to produce a range of novel polyesters. It is shown that the use of secondary diols leads to polymers with higher glass transition temperatures (Tg) than those prepared from their primary diol equivalents. Two methods of polymerisation were investigated, the first employing activation of the aromatic diacids via the corresponding diacid chlorides and the second using a transesterification procedure. Longer chain diols were found to be more reactive than the shorter chain alternatives, generally giving rise to higher molecular weight polymers, an effect shown to be most pronounced when using the transesterification route. Finally, novel diesters with high degrees of branching in their hydrocarbon chains are introduced as potential monomers for possible low surface energy materials applications.

New, potentially chelating NHC ligands; synthesis, complexation studies, and preliminary catalytic evaluation.

Two new N-heterocyclic carbene (NHC) ligands bearing 2-morpholino and 2-piperidinyl naphthyl wingtips were synthesised (2-SIMorNap and 2-SIPipNap). Nuclear magnetic resonance studies, in conjunction with crystal structures and derivatisation of the NHC salts using a chiral counteranion, revealed that the ligand wingtips are oriented anti with respect to each other. From the free carbene, palladium, ruthenium and iridium complexes were prepared. NHC-iridium dicarbonyl complexes were made in order to extract the TEP values for these ligands. The study showed that these NHC ligands are more electron-donating than normal, aryl-substituted NHCs. The palladium complexes were tested in representative Suzuki-Miyaura cross-coupling reactions and compared to the state of the art systems. Ruthenium-catalysed ring-closing metathesis with these ligands was also performed. It was found that Grubbs' 2nd generation catalyst incorporating 2-SIPipNap did not initiate at room temperature and required heating for RCM to occur.

Electrochemical Coupling of Biomass-Derived Acids: New C8 Platforms for Renewable Polymers and Fuels.

Electrolysis of biomass-derived carbonyl compounds is an alternative to condensation chemistry for supplying products with chain length >C6 for biofuels and renewable materials production. Kolbe coupling of biomass-derived levulinic acid is used to obtain 2,7-octanedione, a new platform molecule only two low process-intensity steps removed from raw biomass. Hydrogenation to 2,7-octanediol provides a chiral secondary diol largely unknown to polymer chemistry, whereas intramolecular aldol condensation followed by hydrogenation yields branched cycloalkanes suitable for use as high-octane, cellulosic gasoline. Analogous electrolysis of an itaconic acid-derived methylsuccinic monoester yields a chiral 2,5-dimethyladipic acid diester, another underutilized monomer owing to lack of availability.

Enantioselective Total Synthesis of (+)-Psiguadial B.

The first enantioselective total synthesis of the cytotoxic natural product (+)-psiguadial B is reported. Key features of the synthesis include (1) the enantioselective preparation of a key cyclobutane intermediate by a tandem Wolff rearrangement/asymmetric ketene addition, (2) a directed C(sp(3))-H alkenylation reaction to strategically forge the C1-C2 bond, and (3) a ring-closing metathesis to build the bridging bicyclo[4.3.1]decane terpene framework.

Efficient, chemical-catalytic approach to the production of 3-hydroxypropanoic acid by oxidation of biomass-derived levulinic acid with hydrogen peroxide.

3-Hydroxypropanoic acid (HPA), a precursor to acrylic acid, can be produced in high yield by oxidation of the biomass-derived platform chemical levulinic acid. While treatment of levulinic acid with H2 O2 under acidic conditions gives predominantly succinic acid, a remarkable reversal of selectivity is observed under basic conditions, leading either directly to HPA or, under modified conditions, initially to 3-(hydroperoxy)propanoic acid, which can be quantitatively hydrogenated to HPA.

Efficient ring-closing metathesis of alkenyl bromides: the importance of protecting the catalyst during the olefin approach.

We present the first productive ring-closing metathesis reaction that leads to the construction of cyclic alkenyl bromides. Efficient catalysis employing commercially available Grubbs II catalyst is possible through appropriate modification of the starting bromoalkene moiety.

Highly chemo- and enantioselective synthesis of 3-allyl-3-aryl oxindoles via the direct palladium-catalyzed alpha-arylation of amides.

A new NHC x Pd-catalyzed asymmetric alpha-arylation of amides is reported that gives direct access to synthetically valuable, allylated oxindoles with quaternary carbon centers. The reaction is made possible by the introduction of a new chiral NHC ligand. The palladium complexes derived therefrom combine excellent reactivity with high chemo- and enantioselectivity for the title transformation.