The efficient construction of quaternary carbon centers is a challenging task due to their enhanced structural complexity. Although the catalytic gem‐difunctionalization of α‐diazo carbonyl compounds ...via metal‐carbenoids is well‐documented, developing new methods to access quaternary carbon centers which are difficult or unattainable in monocatalysis is highly desirable. Dual catalysis where two different catalysts work concurrently has emerged as a powerful strategy to achieve new reactivity and selectivity. In this review, we highlight the recent advances in cooperative Rh(II)/Pd(0) dual catalysis for the construction of quaternary carbon centers, focusing on the synthetic utility of stable α‐diazo‐β‐keto‐esters and allylic carboxylates. Additionally, several challenging asymmetric Rh(II)/Pd(0) dual‐catalyzed transformations generating chiral quaternary carbon centers are also discussed.
Efficient construction of quaternary carbon centers is one of the great challenges in organic synthesis. Recent advances in cooperative Rh(II)/Pd(0) dual catalysis that promote the reactions of stable α‐diazo‐β‐keto‐esters (acceptor/acceptor) with allylic carboxylates are summarized. In this process, the catalytically generated Rh(II)‐carbenoids (A) and π‐allyl Pd(II) intermediates (B) are involved. Various all‐ and O‐substituted quaternary carbon centers can be efficiently constructed, in which two bonds at the carbenic center were formed in a straightforward manner.
A chemo‐selective Rh(II)/Pd(0) dual catalysis that promotes one‐pot synthesis of C3‐quaternary allylic oxindoles from N‐aryl‐α‐diazo‐β‐ketoamides and functionalized allyl carbonates in good to ...excellent yields has been developed. The efficiency of this transformation relies on the choice of Rh(II)/Pd(0) dual catalysis strategy that enabled cascade intramolecular aryl C−H insertion and allylic alkylation under mild conditions.
Abstract Lung cancer has been the leading type of cancers with regard to mortality and mobility. New versions of RNAi-based therapy are greatly required to tackle the challenges of lung cancer. In ...this study, we developed a novel siRNA delivery vector based on our magnetic mesoporous silica nanoparticles (M-MSNs) platform. This nanocarrier was constructed by loading siRNAs into the mesopores of M-MSNs, followed by polyethylenimine (PEI) capping, PEGylation and fusogenic peptide KALA modification. The resultant delivery system exhibited prolonged half-life in bloodstream, enhanced cell membrane translocation and endosomal escapablity, and favorable tissue biocompatibility and biosafety. Systemic application of vascular endothelial growth factor (VEGF) siRNA via this nanocarrier resulted in remarkable tumor suppression, both in subdermal and orthotopic lung cancer models, while tumor metastasis was also significantly reduced, overall leading to improved survival. In addition, the magnetic core of the particles and the functionalized fluorescence markers conveniently enabled in vivo imaging of target tissues. Taken together, this M-MSNs-based siRNA delivery vehicle has shown very favorable applicability for cancer therapy.
A novel P,N-bidentate ligand-assisted gold-catalyzed oxidative amination of β-amino-ynones has been developed, allowing the simple and efficient construction of various quaternary ammonium-olate ...salts in good to excellent yields. These unprecedented quaternary ammonium-olate salts can be isolated and purified via simple suction filtration. The broad substrate scope, easy purification, easy further transformation, and mild conditions make it a viable alternative for the synthesis of various quaternary ammonium-olate salts.
The first gold(III)-catalyzed regioselective oxidation/cycloisomerization of diynes 1 with pyridine N-oxide as the oxidant was developed, providing a range of synthetically valuable and useful fused ...furan derivatives 3 in moderate to good yields. Control experiments and the confirmation structure of minor products 5 suggest that this chemistry was a concerted gold(III)-catalyzed oxidation/SN2′-type addition/cyclization process via a β-gold vinyloxypyridinium intermediate and a putative vinyl cation intermediate.
Heterogeneous catalytic reactions based on single metal–organic framework (MOF) material for the oxidative carboxylation of olefins following a tandem process, which involves the epoxidation of ...olefins and subsequent epoxide–CO
2
cycloaddition, are highly desirable and economical for CO
2
chemical fixation. In this work, a new
trans
-A
2
B
2
-type porphyrin ligand, 5,15-di(
m
-benzoato)-porphyrin (H
2
DMBP), was successfully synthesized and utilized for constructing a novel, highly porous, and stable Nd-porphyrin MOF, named CSUST-2. (CSUST stands for Changsha University of Science and Technology.) Furthermore, the coordinatively unsaturated Co(II) ions were implanted into the MOF by exploiting the innate non-metallated porphyrin ligands to generate Co(II)@CSUST-2 framework, which was evidenced to act as an efficient recyclable catalyst for oxidative carboxylation of olefins in the presence of
tert
-butyl hydroperoxide (TBHP) as an oxidant and tetrabutylammonium bromide (
n
-Bu
4
NBr) as a co-catalyst under mild conditions (1 atm CO
2
, 75 °C, and without solvent).
Graphic abstract
Of 26 tigecycline-nonsusceptible Klebsiella pneumoniae (TNSKP) clinical isolates, 25 had nonsynonymous mutations in ramR and/or acrR (23 in ramR and 10 in acrR). Eight TNSKP isolates possessed ...overexpression of ramA, acrB, rarA, and oqxB simultaneously, while 8 and 1 TNSKP strains had upregulation of ramA and acrB and of rarA and oqxB, respectively. Thus, resistance mechanisms of 9 TNSKP isolates cannot be explained by the present pathways. This study underscores the role of RamA in TNSKP and suggests the presence of novel tigecycline resistance mechanisms.
An attractive palladium-catalyzed three-component reaction of ortho-amino aryl diazo esters, allyl carboxylates, and carbon monoxide (CO) has been developed. This catalytic system rendered domino ...carbene migratory insertion and carbonylation. Remarkably, 2-indolones 3 with a C3 all-carbon quaternary center can be selectively obtained in good to excellent yields via one-pot synthesis, in which two different C–C bonds and one C–N bond were formed in a straightforward manner.
Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially ...results from differential
expression, functional single-nucleotide polymorphisms (SNPs) of
were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common
haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of
variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739;
= 0.007). This protective haplotype was associated with lower levels of
and its antisense long noncoding RNA
by
-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the
/
locus by the polymorphisms. The protective rs2066992-
allele disrupted a conserved CTCF-binding locus at the enhancer elements of
, which transcribed antisense to
and induces
expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced
expression and attenuated
induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's
genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients.
Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in
account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated
polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype
, represented by rs1800796, rs1524107, and rs2066992 at the
locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype
-
-
had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the
intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that
genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.
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