Cationic iridium complexes with chiral P,Nligands and tetrakis [3,5-(trifluoromethyl)phenyl]borate (BAr F ) as the counterion are efficient homogeneous catalysts for the enantioselective hydrogenation of olefins. The complexes are readily prepared, air-stable, and easy to handle. In contrast to chiral rhodium-and ruthenium-phosphine catalysts, they do not require the presence of a polar coordinating group near the C C bond. In the hydrogenation of unfunctionalized arylolefins, high enantioselectivities of > 95% ee with turnover numbers of up to 5000 and turnover frequencies of > 5000 h À1 have been achieved.

SUMMARY To elucidate how the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor alirocumab modulates lipoprotein(a) [Lp(a)] plasma levels, the authors performed a series of Lp(a) uptake studies in primary human hepatocytes and dermal fibroblasts and measured Lp(a) secretion from human hepatocytes. They found that Lp(a) cellular uptake occurred in a low-density lipoprotein receptor–independent manner. Neither PCSK9 nor alirocumab altered Lp(a) internalization. By contrast, the secretion of apolipoprotein (a) from human hepatocytes was sharply increased by PCSK9, an effect that was reversed by alirocumab. They propose that PCSK9 does not significantly modulate Lp(a) catabolism, but rather enhances the secretion of Lp(a) from liver cells.

Phosphinooxazolines 1 (phox ligands) have been successfully applied in many different enantioselective metal-catalyzed processes. [1] We have recently found that iridium ± phox complexes are efficient catalysts for the enantioselective hydrogenation of unfunctionalized alkenes, [2] a class of substrates that gives unsatisfactory results with other catalysts. [3] The best enantioselectivities (up to 99 % ee) have been observed for 1-alkyl-1,2-diaryl-substituted alkenes, while other alkenes such as monoaryl-1,2-dimethyl-substituted alkenes are converted with only moderate enantiomeric excesses. Here we report a new class of ligands, the phosphinite ± oxazolines 2, which induce high enantioselectivity with a much broader range of alkenes and, thus, significantly enhance the scope of Ir-catalyzed hydrogenation.Both enantiomers of the phosphinite ± oxazoline ligands 2 are readily prepared in three to four steps, starting from imidates 5 or carboxylic acids 8 and l-serine methyl ester hydrochloride (4) or the corresponding d isomer (Scheme 1). Special precautions had to be taken in the peptide coupling Scheme 1. Synthesis of compounds 2 for which R 3 Ph. a) 4,

Our studies confirm that cabazitaxel is more active in ABCB1(+) cell models due to its reduced affinity for P-gp compared to docetaxel.

Both enantiomers are readily prepared of phosphinite–oxazoline ligands 1 from the D and L enantiomers of serine (see Scheme). Iridium complexes derived from these ligands (the structure of one complex is shown) are excellent catalysts for the enantioselective hydrogenation of unfunctionalized alkenes. R1=ferrocenyl, aryl; R2=alkyl, benzyl.