Monofluorinated alkyl compounds are of great importance in pharmaceuticals, agrochemicals and materials. Herein, we describe a direct nickel‐catalyzed monofluoromethylation of unactivated alkyl ...halides using a low‐cost industrial raw material, bromofluoromethane, by demonstrating a general and efficient reductive cross‐coupling of two alkyl halides. Results with 1‐bromo‐1‐fluoroalkane also demonstrate the viability of monofluoroalkylation, which further established the first example of reductive C(sp3)‐C(sp3) cross‐coupling fluoroalkylation. These transformations demonstrate high efficiency, mild conditions, and excellent functional‐group compatibility, especially for a range of pharmaceuticals and biologically active compounds. Mechanistic studies support a radical pathway. Kinetic studies reveal that the reaction is first‐order dependent on catalyst and alkyl bromide whereas the generation of monofluoroalkyl radical is not involved in the rate‐determining step. This strategy provides a general and efficient method for the synthesis of aliphatic fluorides.
A direct nickel‐catalyzed monofluoroalkylation of unactivated alkyl halides has been established, by demonstrating the first example of reductive C(sp3)−C(sp3) cross‐coupling fluoroalkylation. These transformations exhibited high efficiency, mild conditions, and excellent functional‐group compatibility, especially for a range of pharmaceuticals and biologically active compounds.
The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Phila?delphia chromosome(Ph) and is a hallmark of chronic myeloid leukemia(CML).In leukemia ...cells,Ph not only impairs the physiological signaling pathways but also disrupts genomic stability.This aberrant fusion gene encodes the breakpoint cluster region?proto?oncogene tyrosine?protein kinase(BCR?ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity.The kinase activity is responsible for maintaining proliferation,inhibiting differentia?tion,and conferring resistance to cell death.During the progression of CML from the chronic phase to the accelerated phase and then to the blast phase,the expression patterns of different BCR?ABL1 transcripts vary.Each BCR?ABL1 transcript is present in a distinct leukemia phenotype,which predicts both response to therapy and clinical outcome.Besides CML,the Ph is found in acute lymphoblastic leukemia,acute myeloid leukemia,and mixed?phenotype acute leukemia.Here,we provide an overview of the clinical presentation and cellular biology of different phenotypes of Ph?positive leukemia and highlight key findings regarding leukemogenesis.
Enantioselective synthesis of tetrahydroisoquinolines bearing an all-carbon quaternary stereogenic center, was achieved
via
asymmetric C-H activation with high enantioselectivities (up to 93% ee). ...Fair substrate tolerance was indicated throughout the scope investigation and no evident loss of enantioselectivity was exhibited in late-stage derivatization. This study provides incentives for the construction of diverse chiral isoquinoline derivatives, which are prevalent among pharmaceuticals, natural products,
etc.
Enantioselective synthesis of isoquinoline derivatives bearing an all-carbon quaternary stereocenter in one step
via
asymmetric Pd(
ii
)-catalyzed C-H activation and multiple late-stage derivatizations.
Cooperative spin crossover transitions with thermal hysteresis loops are rarely observed in cobalt(II) complexes. Herein, two new mononuclear cobalt(II) complexes with hysteretic spin crossover at ...relatively high temperatures (from 320 to 400 K), namely, Co(terpy-CH2OH)2·X2 (terpy-CH2OH = 4′-(hydroxymethyl)-2,2′;6′,2″-terpyridine, X = SCN–(1) and SeCN– (2)), have been synthesized and characterized structurally and magnetically. Both compounds are mononuclear CoII complexes with two chelating terpy-CH2OH ligands. Magnetic measurements revealed the existence of the hysteretic SCO transitions for both complexes. For compound 1, a one-step transition with T 1/2↑= 334.5 K was observed upon heating, while a two-step transition is observed upon cooling with T 1/2↓(1) = 329.3 K and T 1/2↓(2) = 324.1 K (at a temperature sweep rate of 5 K/min). As for compound 2, a hysteresis loop with a width of 5 K (T 1/2↓ = 391.6 K and T 1/2↑ = 396.6 K, at a sweep rate of 5 K/min) can be observed. Thanks to the absence of the crystallized lattice solvents, their single crystals are stable enough at high temperatures for the structure determination at both spin states, which reveals that the hysteretic SCO transitions in both complexes originate from the crystallographic phase transitions involving a thermally induced order–disorder transition of the dangling −CH2OH groups in the ligand. This work shows that the modification of the terpy ligand has an important effect on the magnetic properties of the resulting cobalt(II) complexes.
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*Co
III
-catalyzed asymmetric C–H activation reactions, indicating their potential as chiral ligands or catalysts in asymmetric synthesis.
The first example of copper-catalyzed direct formylation of alkenyl C–H bonds for the facile synthesis of α,β-unsaturated aldehydes has been developed. This transformation has demonstrated high ...reactivity, mild reaction conditions and a broad substrate scope. BrCHCl2 is expected to be developed as an efficient stoichiometric C1 building block in organic synthesis.
Circular RNAs (circRNAs) are a class of non-coding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. They are structurally stable and ...tissue-specific. However, the function of human circRNAs and the role of circRNAs in papillary thyroid carcinoma (PTC) remain to be determined. Herein, the function of circRNA circBACH2 was investigated in human PTC cells. First, we detected the expression of circBACH2 in PTC tissues and PTC cell lines by RT-PCR. FISH was used to confirm the subcellular localization of circBACH2. A luciferase reporter assay and AGO2-RIP was used to confirm the relationship between circBACH2 and miR-139-5p. PTC cells were stably transfected with siRNA against circBACH2 and cell proliferation, migration and invasion were detected to evaluate the effect of circBACH2 in PTC, while tumorigenesis was assayed in nude mice. We found that circBACH2 was highly expressed in PTC tissues and PTC cell lines. Mechanistically, we confirmed that circBACH2 could directly bind to miR-139-5p and relieve suppression of the target LMO4. Functionally, we found that inhibiting circBACH2 expression decreased cell proliferation, migration, and invasion. Finally, down-regulating circBACH2 suppressed the growth of PTC xenografts in nude mice. Our findings indicate that circBACH2 acts as a novel oncogenic RNA that sponges miR-139-5p and can be used as a tumor biomarker of PTC. What's more, these results revealed that the circBACH2/miR-139-5p/LMO4 axis could be targeted as a potential treatment strategy for PTC.
Comprehensive Summary
While drug chirality remains one of the most important themes in medicinal chemistry and fluorine‐containing drugs have comprised large portion of global pharmaceutical market, ...the synthesis of fluorine‐containing compounds featuring a trifluoromethylated stereogenic carbon center is still underdeveloped. Recent strategy of enantioconvergent cross‐coupling of trifluoromethylated alkyl halide has significantly updated previous toolbox that is dependent on additional functional group to achieve desired bond formation and highly enantioselective control. However, evident limitations were present in specific coupling candidate (sp2 carbon) and/or prerequisite heteroatom in trifluoroalkyl source for inducing effective stereoconvergent differentiation. Leveraging novel design of sterically hindered bisoxazoline ligand and drastic increase of molecular complexity of in situ generated sp3 coupling partner via metal‐hydride atom transfer, herein, we report a nickel‐catalyzed, highly enantioselective hydrotrifluoroalkylation of unactivated alkenes for diverse synthesis of enantioenriched aliphatic alkanes featuring trifluoromehylated stereogenic carbon. Excellent stereochemical control (mostly >95: 5 er), high catalytic reactivity, mild conditions, and broad substrate scope (40+ examples), enable convenient late‐stage asymmetric trifluoroalkylation of various biologically active complex molecules.
Recent strategy of enantioconvergent cross‐coupling of trifluoromethylated alkyl halide has significantly updated previous toolbox that is dependent on additional functional group to achieve desired bond formation and highly enantioselective control. However, evident limitations were present in specific coupling candidate (sp2 carbon) and/or prerequisite heteroatom in trifluoroalkyl source for inducing effective stereoconvergent differentiation. Leveraging novel design of sterically hindered bisoxazoline ligand and drastic increase of molecular complexity of in situ generated sp3 coupling partner via metal‐hydride atom transfer, herein, we report a nickel‐catalyzed, highly enantioselective hydrotrifluoroalkylation of unactivated alkenes for diverse synthesis of enantioenriched aliphatic alkanes featuring trifluoromehylated stereogenic carbon with excellent stereochemical control (mostly >95: 5 er), high catalytic reactivity, and broad substrate scope (> 40 examples).
In the extracorporeal shock wave lithotripsy for infants, we used a medical polymer gel pad to assist ultrasonic positioning, so that the ultrasonic probe could be far away from the shock wave energy ...field. Although not affecting the ultrasonic positioning and monitoring effect, we discussed the protective effect of this method on the ultrasonic probe. A retrospective analysis was made on 21 infants (0–3 years old) who received ESWL in our hospital from June 2021 to February 2023. After the stones were accurately located by B-ultrasound before surgery, a 4 * 5 * 10 cm medical polymer gel pad was placed between the skin and the ultrasonic probe to keep the ultrasonic probe away from the shock wave energy field. The B-ultrasonic wave source locked the target stone through the gel pad, and the lithotripter Dornier Compact Delta II was used for lithotripsy. The extracorporeal shock wave lithotripsy was completed under the whole process of B-ultrasonic monitoring. All patients completed the surgery under ultrasound monitoring, and there were no abnormalities in the ultrasound probe during the surgery. The average stone size was 0.60 ± 0.21 cm, the surgical time was 39.8 ± 13.8 min, and the total energy of lithotripsy was 7.41 ± 4.35 J. There were no obvious complications in all patients after the surgery. After 2 weeks of ultrasound examination, the success rate of lithotripsy in 21 patients reached 85.7%. We believe that the use of the gel pad increases the distance between the ultrasonic probe and the skin, leaving the probe away from the shock wave energy field, avoiding the damage of the shock wave source to the ultrasonic probe, and does not affect the monitoring effect of ultrasound on stones and the success rate of lithotripsy, which is worthy of further promotion in the field of children’s urinary stones.
The Toll signaling pathway plays an important role in animal innate immunity. However, its activation and signal transmission greatly differ across species and need to be investigated. Shrimp farming ...is a worldwide economic activity affected by bacterial disease from the 1990s, which promoted research on shrimp immunity. In this study, we first proved that, among the three identified Toll receptors in
kuruma shrimp, Toll 3 plays a pivotal role in initiating the antibacterial response
, especially upon anti-
infection. Further research showed that this result was due to the activation of the Dorsal transcription factor, which induced the expression of two anti-lipopolysaccharide factors (Alfs). Moreover, the evolutionarily conserved signaling intermediate in Toll pathways, ECSIT, was proved to be needed for signal transmission from Toll 3 to Dorsal and the expression of anti-lipopolysaccharide factors. Finally, the mortality assay showed that a Toll3-ECSIT-Dorsal-Alf axis was functional in the anti-
immunity of
shrimp. The results provide new insights into the function and signal transduction of the Toll pathway in aquatic species and offer basic knowledge for shrimp disease control and genetic breeding.
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