Abbreviations: Drp1, dynamin-related protein 1; Drp1 K38A, mutant mouse Drp1 plasmid in which lysine 38 is substituted by alanine; Drp1 WT, wild-type mouse Drp1 plasmid; Drpitor, Drp1 inhibitor; Fis1, mitochondrial fission 1 protein; GMP-PNP, guanosine 5′-[β,γ-imido]triphosphate; HA, hemagglutinin; IC50, half maximal inhibitory concentration; IR, ischemia-reperfusion; mdivi-1, mitochondrial division inhibitor 1; MFC, mitochondrial fragmentation count; MFF, mitochondrial fission factor; MiD49, mitochondrial dynamics protein of 49 kDa; MiD51, mitochondrial dynamics protein of 51 kDa; OMM, outer mitochondrial membrane; ROS, reactive oxygen species; RV, right ventricle; RVEDP, right ventricular end-diastolic pressure; siDrp1, small interfering RNA against Drp1.
AbstractMitochondrial fission is important in physiological processes, including coordination of mitochondrial and nuclear division during mitosis, and pathologic processes,
Conjugate addition of arylboronates to α,β-unsaturated ketones may be catalyzed by chiral binaphthols with enantioselectivities of up to 99:1. Best results were observed with 3,3'-dichloro-BINOL. This chemistry was applied to syntheses of intermediates for syntheses of (+)-indatraline and (+)-tolterodine.
Proton abstraction of N-tert-butoxycarbonyl-piperidine (N-Boc-piperidine) with sBuLi and TMEDA provides a racemic organolithium that can be resolved using a chiral ligand. The enantiomeric organolithiums can interconvert so that a dynamic resolution occurs. Two mechanisms for promoting enantioselectivity in the products are possible. Slow addition of an electrophile such as trimethylsilyl chloride allows dynamic resolution under kinetic control (DKR). This process occurs with high enantioselectivity and is successful by catalysis with substoichiometric chiral ligand (catalytic dynamic kinetic resolution). Alternatively, the two enantiomers of this organolithium can be resolved under thermodynamic control with good enantioselectivity (dynamic thermodynamic resolution, DTR). The best ligands found are based on chiral diamino-alkoxides. Using DTR, a variety of electrophiles can be used to provide an asymmetric synthesis of enantiomerically enriched 2-substituted piperidines, including (after Boc deprotection) the alkaloid (+)-beta-conhydrine. The chemistry was extended, albeit with lower yields, to the corresponding 2-substituted seven-membered azepine ring derivatives.
[reaction: see text] Total syntheses of enantiopure hanishin, longamide B, and longamide B methyl ester are described. Absolute configurations of these natural products have been established.
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