Regioselective Markovnikov hydrodifluoroalkylation of alkenes using difluoroenoxysilanes.

Alkene hydrodifluoroalkylation is a fruitful strategy for synthesizing difluoromethylated compounds that are interesting for developing new medicinal agents, agrochemicals, and advanced materials. Whereas the anti-Markovnikov hydrodifluoroalkylation to linear-type products is developed, employing radical-based processes, the Markovnikov synthesis of branched adducts remains unexplored. Herein, we describe acid-catalyzed processes involving carbocation intermediates as a promising strategy to secure the Markovnikov regioselectivity. Accordingly, the Markovnikov hydrodifluoroalkylation of mono-, di-, tri-, and tetrasubstituted alkenes using difluoroenoxysilanes, catalyzed by Mg(ClO4)2·6H2O, is achieved. This allows the diversity-oriented synthesis of α,α-difluoroketones with a quaternary or tertiary carbon at the ß-position that are otherwise difficult to access. The method is applied to the modification of natural products and drug derivatives. The resulting α,α-difluorinated ketones could be converted to the corresponding α,α-difluorinated esters or alcohols, or organofluorine compounds featuring a CF2H or CF2CF2Ph moiety. Mechanistic studies support that Mg(ClO4)2·6H2O functions as a hidden Brønsted acid catalyst.

Activation of Chiral (Salen)TiCl2 Complex by Phosphorane for the Highly Enantioselective Cyanation of Nitroolefins.

We report that phosphorane can activate (salen)TiCl2 complex to achieve unprecedented excellent enantioselectivity and a broad substrate scope in the cyanation of nitroolefins. Our cyanating reagent Me2(CH2Cl)SiCN proves to be more active than TMSCN in this reaction, allowing 11 ß-aliphatic nitrolefins and 12 ß-CF3 nitroolefins (either ß-aryl or aliphatic) to work well to give the corresponding tertiary or quaternary ß-nitronitriles with high to excellent enantioselectivity.

H-bond donor-directed switching of diastereoselectivity in the Michael addition of α-azido ketones to nitroolefins.

The development of catalyst-controlled stereodivergent asymmetric catalysis is important for providing facile access to all stereoisomers of chiral products with multiple stereocenters from the same starting materials. Despite progress, new design strategies for diastereodivergent asymmetric catalysis are still highly desirable. Here we report the potency of H-bond donors as the governing factor to tune diastereoselectivity in a highly diastereoselective switchable enantioselective Michael addition of α-azido ketones to nitroolefins. While a newly developed bifunctional tertiary amine, phosphoramide, preferentially afforded syn-adducts, an analogous squaramide catalyst selectively gave anti-adducts. The resulting multifunctional tertiary azides can be converted to spiro-pyrrolidines with four continuous stereocenters in a one-pot operation. Mechanistic studies cast light on the control of diastereoselectivity by H-bond donors. While the squaramide-catalyzed reaction proceeded with a transition state with both squaramide N-H bonds binding to an enolate intermediate, an unprecedented model was proposed for the phosphoramide-mediated reaction wherein an amide N-H bond and an alkylammonium ion formed in situ interact with nitroolefins, with the enolate stabilized by nonclassical C-H⋯O hydrogen-bonding interactions.

Biginkgosides A-I, Unexpected Minor Dimeric Flavonol Diglycosidic Truxinate and Truxillate Esters from Ginkgo biloba Leaves and Their Antineuroinflammatory and Neuroprotective Activities.

Nine unexpected new flavonol glycoside cyclodimers in the truxinate (1-7, biginkgosides A-G, respectively) or truxillate [biginkgosides H (8) and I (9)] forms were isolated as minor components from the extract of Ginkgo biloba leaves. The new dimers possess an unusual cyclobutane ring formed by a [2+2]-cycloaddition between two symmetric (for compounds 1-5 and 7-9) or nonsymmetric (for 6) flavonol coumaroyl glucorhamnosides. A plausible biosynthetic pathway for these new compounds based on the frontier molecular orbital theory of cycloaddition reactions is briefly discussed. An antineuroinflammatory screening revealed that biginkgosides E (5) and H (8) inhibited nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells, with IC50 values of 2.91 and 17.23 µM, respectively. Additionally, biginkgoside F (6) showed a significant neuroprotective effect (34.3% increase in cell viability at 1 µM) against Aß25-35-induced cell viability decrease in SH-SY5Y neuroblastoma cells.

Assessment of right ventricular function by pressure-volume loops in off-pump coronary artery bypass surgery.

BACKGROUND: Right ventricular function plays an important role in the hemodynamic derangement during off-pump coronary artery bypass (OPCAB) surgery. Pressure-volume loops have been shown to provide load-independent information of cardiac function. Therefore, the aim of this study was to investigate the feasibility of construction of right ventricular pressure-volume loops with pressure and volume data measured by a volumetric pulmonary artery catheter (PAC) and to evaluate right ventricular systolic and diastolic function by end-systolic elastance (E(ES)) and end-diastolic stiffness (E(ED)) in OPCAB surgery. METHODS: Twenty-eight patients who underwent OPCAB surgery were included. After anesthesia induction, a volumetric PAC was placed via the right internal jugular vein. Data were recorded at: anesthesia steady-state before skin incision (T1); 5 minutes after the stabilizer device was placed for anastomosis on the heart's anterior wall (T2), lateral wall (T3), posterior wall (T4), respectively; after sternal closure (T5). Three sets of data were collected at each time point: first, hemodynamic variables were measured; second, right ventricular E(ES) and E(ED) were calculated; third, right ventricular pressure-volume loops were constructed with pressure and volume data measured from end-diastole point, end-isovolumic systole point, peak-ejection point, end-systole point and end-isovolumic diastole point. RESULTS: Right ventricular pressure-volume loops generally shifted to the left during OPCAB surgery. Especially, the end-diastolic point shifted upward and to the left at T2-T5 compared with that at T1. Decrease in right ventricular ejection fraction, stroke volume index and end-diastolic volume index occurred (P < 0.05) at T4 compared with values at T1. Pulmonary vascular resistance index at T4 increased relatively compared with that at T2 and T3. The change of E(ES) was not statistically significant during operation. Right atrial pressure increased only during coronary anastomoses (T2-T4, P < 0.05), whereas E(ED) increased throughout OPCAB surgery (P < 0.05). CONCLUSIONS: Right ventricular pressure-volume loops can be constructed using a volumetric PAC. Right ventricular systolic dysfunction occurred during anastomoses on the heart's posterior wall not due to impaired myocardial contractility but as a result of reduced preload and a relative increase in afterload. Right ventricular diastolic function was impaired throughout OPCAB surgery.