The carbon dioxide (CO2) capture and utilization has attracted a great attention in organic synthesis. Herein, an unpresented transient stabilization effect (TSE) of CO2 is disclosed and well applied ...to the electrochemical hydrogenation of azo compounds to hydrazine derivatives. Mechanistic experiments and computational studies imply that CO2 can capture azo radical anion intermediates to protect the hydrogenation from potential degradation reactions, and is finally released through decarboxylation. The promotion effect of CO2 was further demonstrated to work in the preliminary study of electrochemical reductive coupling of α‐ketoesters to vicinal diol derivatives. For the electrochemical reductive reactions mentioned above, CO2 is indispensable. The presented results shed light on a different usage of CO2 and could inspire novel experimental design by using CO2 as a transient protecting group.
A new transient stabilization effect (TSE) of CO2 is identified and applied to the electrochemical hydrogenation of azo compounds and the reductive coupling of α‐ketoesters. The TSE influence of CO2 means that overactive intermediates can be captured by CO2 to prevent their decomposition or side reaction to complete the synthesis that is difficult to achieve by direct means. The CO2 can be released later through a decarboxylation process.
The first copper‐catalyzed regiodivergent cyanoboration of internal allenes with B2pin2 (bis(pinacolato)diboron) and NCTS (N‐cyano‐N‐phenyl‐p‐toluenesulfonamide) derivatives is reported. The β,γ‐ and ...α,β‐cyanoborylated products were synthesized with high regio‐ and stereo‐selectivity. Computational studies revealed that nucleophilic addition of allylcopper or related intermediates on cyanation reagent is the regio‐ and stereo‐determining step, while transmetalation with B2pin2 is the rate‐determining step. The nucleophilic addition step proceeds via inner‐sphere mechanism in the CuI/P(o‐tol)3 and CuI/Xantphos (P(o‐tol)3=tris(o‐methylphenyl)phosphine, Xantphos=4,5‐bis(diphenylphosphino)‐9,9‐dimethylxanthene) catalytic systems and via outer‐sphere mechanism in the CuII/Xantphos catalytic system, respectively.
The first copper‐catalyzed regiodivergent cyanoboration of internal allenes with B2pin2 and NCTS derivatives has been developed. MeOH was identified as the necessary additive for the regeneration of LCu‐Bpin species. Computational studies revealed that the copper‐mediated allylic cyanation is the regio‐ and stereo‐determining step, while the MeOH‐assisted transmetalation with B2pin2 is the rate‐determining step.
Pd-catalyzed hydrophosphorylation of alkynes with P(O)-H compounds provided atom-economical and oxidant-free access to alkenylphosphoryl compounds. Nevertheless, the applicable P(O)-H substrates were ...limited to those without a hydroxyl group except H
P(O)OH. It is also puzzling that Ph
P(O)OH could co-catalyze the reaction to improve Markovnikov selectivity. Herein, a computational study was conducted to elucidate the mechanistic origin of the phenomena described above. It was found that switchable mechanisms influenced by the acidity of substrates and co-catalysts operate in hydrophosphorylation. In addition, potential side reactions caused by the protonation of Pd
-alkenyl intermediates with P(O)-OH species were revealed. The regeneration of an active Pd(0) catalyst from the resulting Pd(II) complexes is remarkably slower than the hydrophosphonylation, while the downstream reactions, if possible, would lead to phosphorus 2-pyrone. Further analysis indicated that the side reactions could be suppressed by utilizing bulky substrates or ligands or by decreasing the concentration of P(O)-OH species. The presented switchable mechanisms and side reactions shed light on the co-transformations of P(O)-H and P-OH compounds in the Pd-catalyzed hydrophosphorylation of alkynes, clarify the origin of the distinct performances of P(O)-H/OH compounds, and provide theoretical clues for expanding the applicable substrate scope of hydrophosphorylation and synthesizing cyclic alkenylphosphoryl compounds.
Cu-catalyzed aerobic reactions are a powerful protocol for the synthesis of value-added chemicals based on the ideal oxidant O2. Despite the long research history, the mechanistic studies clarifying ...the details of the whole catalytic cycle, where Cu-O2 complexes and their derivatives directly participate in the conversion of substrates, are limited, leaving the mechanisms of emerging aerobic reactions far from understanding. Herein, a computational study on the mechanism of Cu-catalyzed aerobic aminooxygenation of alkene-tethered amides to imides is reported. It is found that the Cu(I) precursor is not the active species but can generate two types of Cu(II) complexes LCu(OAc)OH and LCu(OAc)OOR to start the aminooxygenation through the successive formation of dinuclear Cu(III) oxo complex, dinuclear Cu(II) hydroxide complex, and hetero-dinuclear Cu(II)-Cu(I) complex, followed by alkylperoxo radical capture with Cu(I) species. LCu(OAc)OH catalyzes the aminooxygenation via a mononuclear mechanism, while LCu(OAc)OOR is an active intermediate therein. In the initial catalytic stage, LCu(OAc)OH transforms alkene-tethered amides to α-amidated aldehydes through N–H activation, amide isomerization, cyclization, alkyl radical release, alkyl radical capture by O2, alkylperoxo radical capture by in situ-generated Cu(I) species to LCu(OAc)OOR, acetate-assisted proton-coupled electron transfer (PCET), and concerted PCET/O–O bond cleavage. In the second catalytic stage for the generation of imides from α-amidated aldehydes, the previously proposed aldehyde Cα–H pathway is possible, but it is more likely to generate CO2 and H2 as the byproducts. Instead, a more feasible pathway involving C(O)–H activation to acyl radical, decarbonylation, and radical capture to LCu(OAc)OOR′ was discovered. The C(O)–H activation pathway generates CO and H2O as the byproducts and is consistent with the experimental observations. The concerted PCET/O–O bond cleavage steps generating α-amidated aldehydes and imides have close energy barriers and both can be the rate-determining steps. The presented outcome revised and expanded the knowledge of Cu-catalyzed aerobic conversion of CC bonds and amide N–H bonds, highlighting the different roles of mononuclear and dinuclear copper complexes in the aerobic reactions and the in situ generation of Cu(II) catalysts, respectively.
The first copper‐catalyzed regiodivergent cyanoboration of internal allenes with B2pin2 (bis(pinacolato)diboron) and NCTS (N‐cyano‐N‐phenyl‐p‐toluenesulfonamide) derivatives is reported. The β,γ‐ and ...α,β‐cyanoborylated products were synthesized with high regio‐ and stereo‐selectivity. Computational studies revealed that nucleophilic addition of allylcopper or related intermediates on cyanation reagent is the regio‐ and stereo‐determining step, while transmetalation with B2pin2 is the rate‐determining step. The nucleophilic addition step proceeds via inner‐sphere mechanism in the CuI/P(o‐tol)3 and CuI/Xantphos (P(o‐tol)3=tris(o‐methylphenyl)phosphine, Xantphos=4,5‐bis(diphenylphosphino)‐9,9‐dimethylxanthene) catalytic systems and via outer‐sphere mechanism in the CuII/Xantphos catalytic system, respectively.
The first copper‐catalyzed regiodivergent cyanoboration of internal allenes with B2pin2 and NCTS derivatives has been developed. MeOH was identified as the necessary additive for the regeneration of LCu‐Bpin species. Computational studies revealed that the copper‐mediated allylic cyanation is the regio‐ and stereo‐determining step, while the MeOH‐assisted transmetalation with B2pin2 is the rate‐determining step.
The carbon dioxide (CO2) capture and utilization has attracted a great attention in organic synthesis. Herein, an unpresented transient stabilization effect (TSE) of CO2 is disclosed and well applied ...to the electrochemical hydrogenation of azo compounds to hydrazine derivatives. Mechanistic experiments and computational studies imply that CO2 can capture azo radical anion intermediates to protect the hydrogenation from potential degradation reactions, and is finally released through decarboxylation. The promotion effect of CO2 was further demonstrated to work in the preliminary study of electrochemical reductive coupling of α‐ketoesters to vicinal diol derivatives. For the electrochemical reductive reactions mentioned above, CO2 is indispensable. The presented results shed light on a different usage of CO2 and could inspire novel experimental design by using CO2 as a transient protecting group.
A new transient stabilization effect (TSE) of CO2 is identified and applied to the electrochemical hydrogenation of azo compounds and the reductive coupling of α‐ketoesters. The TSE influence of CO2 means that overactive intermediates can be captured by CO2 to prevent their decomposition or side reaction to complete the synthesis that is difficult to achieve by direct means. The CO2 can be released later through a decarboxylation process.
Abstract
The carbon dioxide (CO
2
) capture and utilization has attracted a great attention in organic synthesis. Herein, an unpresented transient stabilization effect (TSE) of CO
2
is disclosed and ...well applied to the electrochemical hydrogenation of azo compounds to hydrazine derivatives. Mechanistic experiments and computational studies imply that CO
2
can capture azo radical anion intermediates to protect the hydrogenation from potential degradation reactions, and is finally released through decarboxylation. The promotion effect of CO
2
was further demonstrated to work in the preliminary study of electrochemical reductive coupling of α‐ketoesters to vicinal diol derivatives. For the electrochemical reductive reactions mentioned above, CO
2
is indispensable. The presented results shed light on a different usage of CO
2
and could inspire novel experimental design by using CO
2
as a transient protecting group.
Abstract
The carbon dioxide (CO
2
) capture and utilization has attracted a great attention in organic synthesis. Herein, an unpresented transient stabilization effect (TSE) of CO
2
is disclosed and ...well applied to the electrochemical hydrogenation of azo compounds to hydrazine derivatives. Mechanistic experiments and computational studies imply that CO
2
can capture azo radical anion intermediates to protect the hydrogenation from potential degradation reactions, and is finally released through decarboxylation. The promotion effect of CO
2
was further demonstrated to work in the preliminary study of electrochemical reductive coupling of α‐ketoesters to vicinal diol derivatives. For the electrochemical reductive reactions mentioned above, CO
2
is indispensable. The presented results shed light on a different usage of CO
2
and could inspire novel experimental design by using CO
2
as a transient protecting group.
Glyceraldehyde-3-phosphate dehydrogenase （GAPDH）, initially identified as a glycolytic enzyme and considered as a housekeeping gene, is widely used as an internal control in experiments on proteins, ...mRNA, and DNA. However, emerging evidence indicates that GAPDH is implicated in diverse functions independent of its role in energy metabolism; the expression status of GAPDH is also deregulated in various cancer cells. One of the most common effects of GAPDH is its inconsistent role in the determination of cancer cell fate. Furthermore, studies have described GAPDH as a regulator of cell death; other studies have suggested that GAPDH participates in tumor progression and serves as a new therapeutic target. However, related regulatory mechanisms of its numerous cellular functions and deregulated expression levels remain unclear. GAPDH is tightly regulated at transcriptional and pnsttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Several cancer-related factors, such as insulin, hypoxia inducible factor-1 （HIF-1）, p53, nitric oxide （NO）, and acetylated histone, not only modulate GAPDH gene expression but also affect protein functions via common pathways. Moreover, posttranslational modifications （PTMs） occurring in GAPDH in cancer cells result in new activities unrelated to the original glycnlytic function of GAPDH. In this review, recent findings related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms and pathways involved in GAPDH regulation and its different roles in cancer cells are also described.
AIM:To explore the correlation between Twist-related protein(Twist)1,fibroblast growth factor receptor(FGFR)2 and gastric adenocarcinoma differentiation and progression.METHODS:We evaluated Twist1 ...and FGFR2 in 52 gastric adenocarcinoma samples by immunohistochemistry and quantitative real time polymerase chain reaction,and analyzed the correlation between Twist1,FGFR2 and cancer differentiation.We also detected Twist1 and FGFR2 expression in gastric adenocarcinoma cell lines,and evaluated Twist1 influence on FGFR2 expression.In addition,we studied the role of FGFR2 in Twist1-promoted cancer progression,including proliferation,invasion and epithelial-mesenchymal transition(EMT).RESULTS:Twist1 and FGFR2 were detected in almost all the gastric adenocarcinoma samples.Twist1(P=0.0213)and FGFR2(P=0.0310)m RNA levels had a significant association with gastric adenocarcinoma differentiation.Moreover,Twist1 and FGFR2 expression in poorly differentiated cells(SNU-1 and SNU-16)was notably higher than in well-differentiated cells(MKN-7 and MKN-28).In poorly differentiated gastric adenocarcinomas,FGFR2 m RNA level was significantly positively correlated with Twist1 m RNA level(P=0.004).Twist1 was proved to promote FGFR2 by regulating Twist1 expression by knockdown and overexpression.Additionally,Twist1 could induce proliferation,invasion and EMT in gastric cancer;of these,FGFR2 was required for invasion and EMT,rather than proliferation.CONCLUSION:Twist1 and FGFR2 are highly associated with differentiation of gastric adenocarcinoma;Twist1 can facilitate invasion and EMT in gastric adenocarcinoma via promotion of FGFR2 expression.
