Atroposelective synthesis of axially chiral biaryls by palladium‐catalyzed C−H olefination, using tert‐leucine as an inexpensive, catalytic, and transient chiral auxiliary, has been realized. This ...strategy provides a highly efficient and straightforward access to a broad range of enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (95 to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (95 to >99 % ee, s‐factor up to 600).
No attachements: The title reaction employs tert‐leucine as a transient chiral auxiliary and provides efficient access to enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (up to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (up to >99 % ee, s‐factor up to 600).
Background and Aims
Cancer‐associated fibroblasts (CAFs) are key players in multicellular, stromal‐dependent alterations leading to HCC pathogenesis. However, the intricate crosstalk between CAFs and ...other components in the tumor microenvironment (TME) remains unclear. This study aimed to investigate the cellular crosstalk among CAFs, tumor cells, and tumor‐associated neutrophils (TANs) during different stages of HCC pathogenesis.
Approach and Results
In the HCC‐TME, CAF‐derived cardiotrophin‐like cytokine factor 1 (CLCF1) increased chemokine (C‐X‐C motif) ligand 6 (CXCL6) and TGF‐β secretion in tumor cells, which subsequently promoted tumor cell stemness in an autocrine manner and TAN infiltration and polarization in a paracrine manner. Moreover, CXCL6 and TGF‐β secreted by HCC cells activated extracellular signal‐regulated kinase (ERK) 1/2 signaling of CAFs to produce more CLCF1, thus forming a positive feedback loop to accelerate HCC progression. Inhibition of ERK1/2 or CLCF1/ciliary neurotrophic factor receptor signaling efficiently impaired CLCF1‐mediated crosstalk among CAFs, tumor cells, and TANs both in vitro and in vivo. In clinical samples, up‐regulation of the CLCF1−CXCL6/TGF‐β axis exhibited a marked correlation with increased cancer stem cells, “N2”‐polarized TANs, tumor stage, and poor prognosis.
Conclusions
This study reveals a cytokine‐mediated cellular crosstalk and clinical network involving the CLCF1−CXCL6/TGF‐β axis, which regulates the positive feedback loop among CAFs, tumor stemness, and TANs, HCC progression, and patient prognosis. These results may support the CLCF1 cascade as a potential prognostic biomarker and suggest that selective blockade of CLCF1/ciliary neurotrophic factor receptor or ERK1/2 signaling could provide an effective therapeutic target for patients with HCC.
Understanding molecule transport through nanochannels is fundamental to geophysics, bioengineering, and physical chemistry. Here, molecular dynamics simulations combined with theoretical analysis are ...conducted to investigate hydrocarbon–water mixture flow in organic nanochannels. The flow is sensitive to the mixture compositions. The total flux decreases sharply with hydrocarbon content before the critical value, while it almost holds constant after the critical value, which is attributed to the spontaneous adsorption of hydrocarbon on the organic surface. An effective theory based on updating the Navier–Stokes equation with a slip boundary is proposed and validated to describe the mixture flow in nanochannels. The established quantitative relations between the total flux/slip length and the mixture composition are consistent with the molecular dynamics results.
The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, we ...reported the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination. A novel chiral spiro phosphoric acid, STRIP, was identified as a superior ligand for this transformation. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee). Density functional theory was used to gain a theoretical understanding of the enantioselectivities in this reaction.
The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination is reported. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee).
Abstract
Most inter-basin water diversion projects have been constructed to cope with water shortage problems. These projects usually have multiple reservoirs and pump stations connected to each ...other. Most previous studies focus solely on the operation of reservoirs aiming to supply more water rather than the joint operation of the reservoir-pump station system. Project operations that ignore the pump station may not be cost effective. In addition, future water availability is of great uncertainty that will affect the system's performance. Therefore, the main purpose of this study is to evaluate the tradeoffs between water supply and power net revenue (considering power generation by hydropower stations and power consumption by pump stations) under different water availability scenarios, which can be used to inform policies. A resilience metric is introduced to evaluate the joint system performance. An optimization model including two objectives: social perspective (minimum of total water shortage) and economic perspective (maximum of power net revenue) is considered for the study area: the Hanjiang-to-Weihe River Valley Water Diversion Project. Results mainly show that two objectives are in a contradictory relationship. If future streamflow does not decrease, the water supply sector could at least meet 50% of the water demand in recipient area.
The atroposelective synthesis of axially chiral styrenes remains a formidable challenge due to their relatively lower rotational barriers compared to the biaryl atropoisomers. Herein, we describe the ...construction of axially chiral styrenes through PdII‐catalyzed atroposelective C−H olefination, using a bulky amino amide as a transient chiral auxiliary. Various axially chiral styrenes were produced with good yields and high enantioselectivity (up to 95 % yield and 99 % ee). Carboxylic acid derivatives of the resulting axially chiral styrenes showed superior enantiocontrol over the biaryl counterparts in CoIII‐catalyzed enantioselective C(sp3)−H amidation of thioamide. Mechanistic studies suggest that C−H cleavage is the enantioselectivity‐determining step.
Axially chiral styrenes were constructed through a PdII‐catalyzed atroposelective C−H olefination with a bulky amino amide as a transient chiral auxiliary. Various axially chiral styrenes were produced with good yields and high enantioselectivity. Carboxylic acid derivatives of these axially chiral styrenes showed superior enantiocontrol compared to the biaryl counterparts in CoIII‐catalyzed enantioselective C(sp3)−H amidation of ferrocenes.
Biaryl atropisomers are of great importance in natural products, pharmaceuticals, and asymmteric synthesis. The efficient synthesis of these chiral scaffolds with full enantiocontrol and high ...diversity remains challenging. Reported herein is a Pd‐catalyzed atroposelective C−H allylation with tert‐leucine as an efficient catalytic chiral transient auxiliary. A wide range of enantioenriched biaryl aldehydes were prepared in synthetically useful yields with excellent enantioselectivity (up to >99 % ee) through β‐O elimination. The reaction could be carried out on a gram scale without erosion of the ee value. A variety of axially chiral carboxylic acids could be obtained with high enantiopurity. The resulting axially chiral biaryl aldehydes and carboxylic acids might be used in asymmetric synthesis as chiral ligands and/or organocatalysts.
A Pd‐catalyzed atroposelective C−H allylation with allylic surrogates is reported. tert‐Leucine was identified as an efficient catalytic transient chiral auxiliary. A range of enantioenriched biaryls were prepared in synthetically useful yields with enantioselectivities up to >99 % ee through β‐O elimination. The reaction could be scaled up and the products could be further converted into enantiomerically pure axially chiral carboxylic acids.
Dibenzocyclooctadiene lignans are an interesting class of molecules because of their unique structure based on an axially chiral biaryl moiety as well as their significant biological activity. ...Herein, we describe the development of a palladium‐catalyzed atroposelective C−H alkynylation and its application in gram‐scale, stereocontrolled formal syntheses of (+)‐isoschizandrin and (+)‐steganone. tert‐Leucine was identified as an efficient, catalytic transient chiral auxiliary. A wide range of enantiomerically enriched biaryl compounds were prepared by this approach in good yields (up to 99 %) with excellent enantioselectivity (up to >99 % ee).
Locked into position with a Pd key: A palladium‐catalyzed atroposelective C−H alkynylation was developed and applied to gram‐scale, stereocontrolled formal syntheses of (+)‐isoschizandrin (see scheme) and (+)‐steganone. tert‐Leucine was identified as an efficient catalytic transient chiral auxiliary for this transformation, which enabled the preparation of a wide range of enantiomerically enriched biaryl compounds in good yields.
Chiral aldehyde catalysis opens new avenues for the activation of simple amines. However, the lack of easy access to structurally diverse chiral aldehyde catalysts has hampered the development of ...this cutting‐edge field. Herein, we report a Pd‐catalyzed atroposelective C−H naphthylation with 7‐oxabenzonorbornadienes for the preparation of axially chiral biaryls with excellent enantioselectivities (up to >99 % ee). This reaction is scalable and robust, which serves as a key step to provide a rapid access to axially chiral aldehyde catalysts through a three‐step C−H functionalization sequence. These chiral aldehydes exhibit better activities and enantioselectivities than the previously reported organocatalysts in the asymmetric activation of glycine derived amides and dipeptides. Moreover, preliminary investigation also discloses that the aldehyde catalyst can effectively override the intrinsic facial selectivity of chiral dipeptide substrates, showcasing the strong chiral induction ability of this type of novel aldehyde catalysts.
A concise synthetic route to chiral aldehyde catalysts with Pd‐catalyzed atroposelective C−H naphthylation as a key reaction is reported. These chiral aldehyde catalysts were successfully employed as ligands in the asymmetric activation of glycine esters enabling a higher level of asymmetric induction and reaction activity. A wide range of enantioenriched biaryls were prepared in synthetically useful yields with excellent enantioselectivities (up to >99 % ee).
The atroposelective synthesis of atropisomers with vicinal diaxes remains rare and challenging, due to the steric influence between the two axes and their unique topology. Herein, we disclose a ...single‐step construction of atropisomers with vicinal C−C and C−N chiral diaxes by cyclopentadiene (Cp)‐free cobalt‐catalyzed intramolecular atroposelective C−H annulation, providing the desired diaxial atropisomers of unique structures with decent stereocontrols of both axes (up to >99 % ee and 70 : 1 dr). The optically pure products bearing fluorophores show circular polarized luminescence (CPL) properties, being candidate materials for potential CPL applications. Atropisomerization experiments and density function theory (DFT) calculations are conducted to study the rotational barriers and rotation pathways of the diaxes.
A single‐step construction of atropisomers with vicinal C−C and C−N chiral diaxes by cyclopentadiene (Cp)‐free cobalt‐catalyzed intramolecular atroposelective C−H annulation with decent stereocontrols (up to >99 % ee and 70/1 dr) was reported. Atropisomerization experiments and DFT calculations are done to study the rotational barriers and pathways of the diaxes.
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