Enantioselective Pd-catalyzed allylic alkylation of indoles by a new class of chiral ferrocenyl P/S ligands.

Chiral ferrocenyl heterobidentate P/S ligands bearing both central and planar chirality were prepared from (S)-Ugi's amine via a three-step modular synthesis. Through systematic screening and optimization, L8 was found to be the best ligand for Pd-catalyzed asymmetric allylic alkylation of indoles with ee's up to 96% being attained.

Highly enantioselective phenyl transfer to aryl aldehydes catalyzed by easily accessible chiral tertiary aminonaphthol.

A new chiral tertiary aminonaphthol ligand 3b served as a highly efficient ligand for the asymmetric catalytic phenyl transfer to aromatic aldehydes and a variety of chiral diarylmethanols was prepared in high ee values (ee up to 99%) and chemical yields. The straightforward syntheses of both 3b and its enantiomer provide an excellent opportunity for large-scale applications.

Remarkably diastereoselective synthesis of a chiral biphenyl diphosphine ligand and its application in asymmetric hydrogenation.

Essentially complete atropdiastereoselectivity was realized in the preparation of biaryl diphosphine dioxide by asymmetric intramolecular Ullmann coupling and oxidative coupling with central-to-axial chirality transfer. A bridged C(2)-symmetric biphenyl phosphine ligand possessing additional chiral centers on the linking unit of the biphenyl groups was synthesized. No resolution step was required for the preparation of the enantiomerically pure chiral ligand. These findings offer a general and practical tool for the development of previously uninvestigated atropdiastereomeric biaryl phosphine ligands. The diphosphine ligand was found to be highly effective in the asymmetric hydrogenation of alpha- and beta-ketoesters, 2-(6'-methoxy-2'-naphthyl)propenoic acid, beta-(acylamino)acrylates, and enol acetates.

Highly enantioselective 1,4-addition of diorganozinc reagents to cyclic enones using chiral diphosphite ligands derived from H8-binaphthol.

[formula: see text] High enantioselectivities have been achieved in the 1,4-addition of dialkylzincs to 2-cyclopentenone, 2-cyclohexenone, and 2-cycloheptenone with ee values up to 99% by using chiral aryl diphosphite ligands derived from H8-binaphthol.

Apolipoprotein AI efficiently binds to and mediates cholesterol and phospholipid efflux from human but not rat aortic smooth muscle cells.

Aortic smooth muscle cells (SMC) from several animal species have been reported to resist depletion of cellular cholesterol by the major apolipoprotein of HDL, apoAI. Resistance of SMC to this protective action of apoAI, if present in humans, could contribute to the overaccumulation of arterial wall cholesterol seen in atherosclerosis. We investigated the ability of human aortic medial SMC to bind and be depleted of cholesterol and phospholipids by apoAI. In contrast to rat aortic SMC, but similar to human fibroblasts, human SMC were readily depleted of cholesterol by apoAI, measured by a marked depletion of intracellular cholesterol available for esterification, and an increase in cholesterol efflux to the medium. Human SMC were also actively depleted of the phospholipids phosphatidylcholine and sphingomyelin by apoAI. In contrast, rat SMC released only a small fraction of these cellular phospholipids to apoAI-containing medium. (125)I-labeled apoAI bound with high affinity and specificity to human SMC, but failed to bind to rat SMC. Similar levels of expression of class B, type I scavenger receptor (SR-BI) and caveolin in human and rat SMC suggested these proteins do not account for the differences in apoAI binding or lipid efflux seen in these cells. An enhancer of apolipoprotein-mediated cholesterol efflux, tyrosyl radical-oxidized HDL, markedly amplified the depletion of cholesterol available for esterification in human SMC compared to HDL, but had no enhanced effect in rat SMC. These results show that human SMC bind and are readily depleted of cellular lipids by apoAI, and suggest that apoAI-mediated cholesterol efflux from arterial SMC may contribute significantly to the circulating pool of HDL cholesterol in vivo. The marked difference in apoAI binding to human and rat arterial SMC provides an excellent model to study the nature of the apoAI-cell binding interaction.

Effects of fetal calf serum and disruption of cadherin function on the formation of bile canaliculi between hepatocytes.

The polarization of hepatocytes to form a connected network of bile canaliculi (BC) is necessary for the function of the liver. Hepatocyte polarization may be controlled by soluble factors and/or physical interactions between cells. Monolayer cultures of embryonic chicken hepatocytes in DMEM supplemented with ornithine, dexamethasone, and insulin express BC-specific antigens for at least 7 days. However, BC-specific antigen expression is lost within 3 days of culture initiation in DMEM containing 10% fetal calf serum. The dedifferentiating effects of fetal calf serum (FCS) can be reversed. Furthermore, cultures in medium containing ornithine, dexamethasone, insulin, and 10% FCS appear identical to cultures grown in 10% FCS alone. Thus FCS contains a soluble inhibitor of hepatocyte polarization. Aggregate cultures grown in suspension maintain hepatocyte polarization for 10-12 days. This may be due to the increased cell-cell contact between hepatocytes in aggregate culture or to more normal contact with the extracellular matrix. We have evaluated the role of cadherin-mediated interactions on hepatocyte polarization. Anti-E-cadherin Fab' fragments disrupted the formation of long networks of BC in monolayer cultures but did not stop polarized expression of BC-specific antigens. The BC antigens in anti-E-cadherin-treated cells were concentrated in small areas between cells and were present at lower levels uniformly on the cell surface. These results indicate that E-cadherin is required for the formation of extended BC networks, but that other factors are responsible for maintaining the synthesis and localization of BC-specific antigens.