Enantioselective Construction of C-SCF3 Stereocenters via Nickel Catalyzed Asymmetric Negishi Coupling Reaction.

The construction of the SCF3-containing 1,1-diaryl tertiary carbon stereocenters with high enantioselectivities is reported via a nickel-catalyzed asymmetric C-C coupling strategy. This method demonstrates simple operations, mild conditions and excellent functional group tolerance, with newly designed SCF3-containing synthon, which can be easily obtained from commercially available benzyl bromide and trifluoromethylthio anion in a two-step manner. Further substrate exploration indicated that the reaction system could be extended to diverse perfluoroalkyl sulfide (SC2F5, SC3F7, SC4F9, SCF2CO2Et)-substituted 1,1-diaryl compounds with excellent enantioselectivities. The synthetic utility of this transformation was further demonstrated by convenient derivatization to optical SCF3-containing analogues of bioactive compounds without an apparent decrease in enantioselectivity.

A bivalent inhibitor against TDRD3 to suppress phase separation of methylated G3BP1.

The formation of membrane-less organelles is driven by multivalent weak interactions while mediation of such interactions by small molecules remains an unparalleled challenge. Here, we uncovered a bivalent inhibitor that blocked the recruitment of TDRD3 by the two methylated arginines of G3BP1. Relative to the monovalent inhibitor, this bivalent inhibitor demonstrated an enhanced binding affinity to TDRD3 and capability to suppress the phase separation of methylated G3BP1, TDRD3, and RNAs, and in turn inhibit the stress granule growth in cells. Our result paves a new path to mediate multivalent interactions involved in SG assembly for potential combinational chemotherapy by bivalent inhibitors.

Photoinduced Copper-Catalyzed Monofluoroalkylation of Terminal Alkynes to Propargylic Fluorides.

A photoinduced copper-catalyzed strategy for the monofluoroalkylation of alkynes with readily available monofluoroalkyl triflates was developed. It provides a new protocol to access valuable propargyl fluoride compounds via C-C bond formation by avoiding the use of highly toxic fluorination reagents. This reaction proceeded under mild conditions to afford propargyl monofluorides in moderate to high yields. Preliminary mechanistic studies reveal that a ligand-matched alkynyl copper complex might be the key photoactive substance.

Engineering Escherichia coli for highly efficient production of lacto-N-triose II from N-acetylglucosamine, the monomer of chitin.

BACKGROUND: Lacto-N-triose II (LNT II), an important backbone for the synthesis of different human milk oligosaccharides, such as lacto-N-neotetraose and lacto-N-tetraose, has recently received significant attention. The production of LNT II from renewable carbon sources has attracted worldwide attention from the perspective of sustainable development and green environmental protection. RESULTS: In this study, we first constructed an engineered E. coli cell factory for producing LNT II from N-acetylglucosamine (GlcNAc) feedstock, a monomer of chitin, by introducing heterologous ß-1,3-acetylglucosaminyltransferase, resulting in a LNT II titer of 0.12 g L-1. Then, lacZ (lactose hydrolysis) and nanE (GlcNAc-6-P epimerization to ManNAc-6-P) were inactivated to further strengthen the synthesis of LNT II, and the titer of LNT II was increased to 0.41 g L-1. To increase the supply of UDP-GlcNAc, a precursor of LNT II, related pathway enzymes including GlcNAc-6-P deacetylase, glucosamine synthase, and UDP-N-acetylglucosamine pyrophosphorylase, were overexpressed in combination, optimized, and modulated. Finally, a maximum titer of 15.8 g L-1 of LNT II was obtained in a 3-L bioreactor with optimal enzyme expression levels and ß-lactose and GlcNAc feeding strategy. CONCLUSIONS: Metabolic engineering of E. coli is an effective strategy for LNT II production from GlcNAc feedstock. The titer of LNT II could be significantly increased by modulating the gene expression strength and blocking the bypass pathway, providing a new utilization for GlcNAc to produce high value-added products.

Copper-Catalyzed Enantioselective Arylation via Radical-Mediated C-C Bond Cleavage: Synthesis of Chiral ω,ω-Diaryl Alkyl Nitriles.

The first example of copper-catalyzed ring-opening, enantioselective arylation of cyclic ketoxime esters to access ω,ω-diaryl alkyl nitriles has been developed in high yield (up to 92% yield) with excellent enantioselectivity (up to 91% ee). Side-arm bis(oxazoline) ligand plays a significant role in this asymmetric catalytic transformation, which provides an efficient route to construct diverse chiral ω,ω-diaryl alkyl nitriles. Synthetic utility has also been demonstrated in the further derivatization of the ω,ω-diaryl alkyl nitrile to the corresponding amide.

Nickel-catalyzed reductive monofluoroakylation of alkyl tosylate with bromofluoromethane to primary alkyl fluoride.

A nickel-catalysed direct terminal monofluoromethlyation between alkyl tosylates and a low-cost, industrial raw material bromofluoromethane has been developed. This transformation has demonstrated high efficiency, mild conditions, and good functional-group compatibility. The key to success of this transformation lies in the ligand and mild base selection, ensuring the generation of various terminal monofluormethylation products.

Facile synthesis of axially chiral styrene-type carboxylic acids via palladium-catalyzed asymmetric C-H activation.

A novel method by a one-step introduction of axial chirality and sterically hindered group has been developed for facile synthesis of axially chiral styrene-type carboxylic acids. With the palladium-catalyzed C-H arylation and olefination of readily available cinnamic acid established, this transformation demonstrated excellent yield, excellent stereocontrol (up to 99% yield and 99% ee), and broad substrate scope under mild conditions. The axially chiral styrene-type carboxylic acids produced have been successfully applied to Cp*CoIII-catalyzed asymmetric C-H activation reactions, indicating their potential as chiral ligands or catalysts in asymmetric synthesis.

Production of liquid fuels from Kraft lignin over bimetallic Ni-Mo supported on ZIF-derived porous carbon catalyst.

Non-noble bimetallic NiMo supported on zeolitic imidazolate framework-derived porous carbon (NiMo@FDC) catalyst for lignin depolymerization has been successfully developed. The synergism between Ni and Mo species in NiMo@FDC catalyst could promote the catalytic cleavage of C-O linkages in Kraft lignin. At a low reaction temperature of 240 °C and under 4 MPa H2, the lignin liquefaction yield was 98.85 wt% and minimum coke yield was 1 wt%, particularly when using 10%NiMo@FDC catalyst. Additionally, at a high reaction temperature of 300 °C and under 2 MPa H2, there was an overall yield of 86 wt% of liquid product and 42 wt% of petroleum ether soluble product. The higher heating value (HHV) increased from 27.65 MJ kg-1 to 34.11 MJ kg-1. In the cycling experiment, the bifunctional catalyst also demonstrated reversability and stability. The synergy of Ni hydrogenation sites and Mo coupled adsorption sites identified a possible mechanism path, which could offer considerable potential for lignin depolymerization.