Regio- and enantioselective CuH-catalyzed 1,2- and 1,4-hydrosilylation of 1,3-enynes.

We report a copper-catalyzed ligand-controlled selective 1,2- and 1,4-hydrosilylation of 1,3-enynes, which furnishes enantiomerically enriched propargyl- and 1,2-allenylsilane products in high yields with excellent enantioselectivities (up to 99% ee). This reaction proceeds under mild conditions, shows broad substrate scope for both 1,3-enynes and trihydrosilanes, and displays excellent regioselectivities. Mechanistic studies based on deuterium-labeling reactions and density functional theory (DFT) calculations suggest that allenylcopper is the dominant reactive intermediate under both 1,2- and 1,4-hydrosilylation conditions, and it undergoes metathesis with silanes via selective four-membered or six-membered transition state, depending on the nature of the ligand. The weak interactions between the ligands and the reacting partners are found to be the key controlling factor for the observed regioselectivity switch. The origin of high enantiocontrol in the 1,4-hydrosilylation is also revealed by high level DLPNO-CCSD(T) calculations.

Copper-Catalyzed Enantioselective Desymmetric Protosilylation of Prochiral Diynes: Access to Optically Functionalized Tertiary Alcohols.

In this protocol, a copper-catalyzed desymmetric protosilylation of prochiral diynes was developed. The corresponding products were obtained in moderate to high yields and enantiomeric ratios. This approach provides a simple method for synthesizing functionalized chiral tertiary alcohols in the presence of a chiral pyridine-bisimidazoline (Pybim) ligand.

Notch activation during early mesoderm induction modulates emergence of the T/NK cell lineage from human iPSCs.

A robust method of producing mature T cells from iPSCs is needed to realize their therapeutic potential. NOTCH1 is known to be required for the production of hematopoietic progenitor cells with T cell potential in vivo. Here we identify a critical window during mesodermal differentiation when Notch activation robustly improves access to definitive hematopoietic progenitors with T/NK cell lineage potential. Low-density progenitors on either OP9-hDLL4 feeder cells or hDLL4-coated plates favored T cell maturation into TCRab+CD3+CD8+ cells that express expected T cell markers, upregulate activation markers, and proliferate in response to T cell stimulus. Single-cell RNAseq shows Notch activation yields a 6-fold increase in multi-potent hematopoietic progenitors that follow a developmental trajectory toward T cells with clear similarity to post-natal human thymocytes. We conclude that early mesodermal Notch activation during hematopoietic differentiation is a missing stimulus with broad implications for producing hematopoietic progenitors with definitive characteristics.

Chelation-Controlled Stereospecific Cross-Coupling Reaction between Alkenes for Atroposelective Synthesis of Axially Chiral Conjugated Dienes.

In this protocol, an efficient palladium-catalyzed asymmetric synthesis of axially chiral conjugated dienes via alkenyl C-H olefination is reported. The corresponding atropisomeric styrenes containing a conjugated diene scaffold were obtained in good yields with good enantioselectivities. This synthetic strategy features an easy operation, mild reaction conditions, a wide functionality tolerance, and high efficiency.

Modulation of Staphylococcus aureus spreading by water.

Staphylococcus aureus is known to spread rapidly and form giant colonies on the surface of soft agar and animal tissues by a process called colony spreading. So far, the mechanisms underlying spreading remain poorly understood. This study investigated the spreading phenomenon by culturing S. aureus and its mutant derivatives on Tryptic Soy Agarose (TSA) medium. We found that S. aureus extracts water from the medium and floats on water at 2.5 h after inoculation, which could be observed using phase contrast microscopy. The floating of the bacteria on water could be verified by confocal microscopy using an S. aureus strain that constitutively expresses green fluorescence protein. This study also found that as the density of bacterial colony increases, a quorum sensing response is triggered, resulting in the synthesis of the biosurfactants, phenolic-soluble modulins (PSMs), which weakens water surface tension, causing water to flood the medium surface to allow the bacteria to spread rapidly. This study reveals a mechanism that explains how an organism lacking a flagellar motor is capable of spreading rapidly on a medium surface, which is important to the understanding of how S. aureus spreads in human tissues to cause infections.