Modular Synthesis of Polysubstituted α-Phosphorylated Arenes via the Catellani Strategy.

In this paper, we described a palladium/norbornene-catalyzed ortho-C-H phosphormethylation of aryl iodides using XCH2P(O)RR', offering a reliable method for the modular synthesis of polysubstituted α-phosphorylated arenes. Alkenylation, hydrogenation, cyanation, methylation, and arylation were all viable termination steps compatible with the reaction. This method demonstrates excellent functional group tolerance and can be extended to the late-stage modification of bioactive molecules. Furthermore, the synthetic transformations of the products demonstrate the practical utility of this reaction.

Phosphine-Catalyzed [4 + 3] Annulation of ß'-Acetoxy Allenoates with 1C,3N-Dinucleophiles: Access to Functionalized Azepine Derivatives.

A novel method for the synthesis of functionalized azepine derivatives has been developed through a phosphine-catalyzed [4 + 3] annulation of ß'-acetoxy allenoates with benzimidazole-derived 1C,3N-dinucleophiles. This approach demonstrates high efficiency and yields ranging from moderate to excellent. The reaction exhibits a wide substrate scope under the optimized conditions. Furthermore, an initial exploration of the asymmetric variant of this reaction has been conducted, utilizing phosphine (R)-SITCP as the catalyst.

Non-Coding RNA in Cholangiocarcinoma: An Update.

Cholangiocarcinoma (CCA) is one of the most common tumors with high malignancy. Its incidence is increasing year by year, and it is insidious and easily metastasized, and most patients are already in advanced stages when they are diagnosed. Surgery is an essential treatment for CCA, but the 5-year survival rate is still unsatisfactory due to the low early diagnosis rate and high malignancy of CCA. Therefore, exploring the molecular mechanisms of CCA to find reliable biomarkers and effective therapeutic targets is essential to improve the early diagnosis and survival rate of CCA. Non-coding RNA (ncRNA) is a class of RNA without protein-coding ability, mainly including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). In recent years, numerous pieces of evidence have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA through various mechanisms such as mediating epigenetic, sponge miRNAs regulating the expression of target genes and participating in regulating cancer-related signaling pathways, which provides new approaches and ideas for early diagnosis, prognosis assessment and therapeutic targeting of CCA. In this paper, we review the molecular mechanisms of lncRNAs and circRNAs regulating the progression of CCA in recent years and discuss their potential clinical value in CCA.

Palladium-catalyzed Heck-carbonylation of alkene-tethered carbamoyl chlorides with aryl formates.

We report a palladium-catalyzed Heck-carbonylation of alkene-tethered carbamoyl chlorides by utilizing aryl formates as convenient CO surrogates. One C-O and two C-C bonds are constructed to give diversiform esterified oxindoles/γ-lactams bearing an all-carbon quaternary stereocenter under gas-free conditions. This transformation features a wide substrate scope and good functional group tolerance and can be easily applied to late-stage functionalization.

Synthesis of 1,2-Fused Benzimidazoles by Amine-Initiated [3 + 3] Annulations of ß'-Acetoxy Allenoates with 1C,3N-Bisnucleophiles.

The amine-catalyzed [3 + 3] annulations of ß'-acetoxy allenoates with 1C,3N-bisnucleophiles have been established. Under the optimal reaction conditions, this operationally simple synthetic process works well with a wide substrate scope, delivering novel 1,2-fused benzimidazole derivatives in moderate to good yields. In addition, preliminary attempts on the asymmetric version of this reaction have been explored by using cinchona alkaloid-based tertiary amines.

Little things with significant impact: miRNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has developed into one of the most lethal, aggressive, and malignant cancers worldwide. Although HCC treatment has improved in recent years, the incidence and lethality of HCC continue to increase yearly. Therefore, an in-depth study of the pathogenesis of HCC and the search for more reliable therapeutic targets are crucial to improving the survival quality of HCC patients. Currently, miRNAs have become one of the hotspots in life science research, which are widely present in living organisms and are non-coding RNAs involved in regulating gene expression. MiRNAs exert their biological roles by suppressing the expression of downstream genes and are engaged in various HCC-related processes, including proliferation, apoptosis, invasion, and metastasis. In addition, the expression status of miRNAs is related to the drug resistance mechanism of HCC, which has important implications for the systemic treatment of HCC. This paper reviews the regulatory role of miRNAs in the pathogenesis of HCC and the clinical applications of miRNAs in HCC in recent years.

Synthesis of 3-Thiocyanobenzothiophene via Difunctionalization of Active Alkyne Promoted by Electrochemical-Oxidation.

A novel and green method for the synthesis of 3-thiocyanatobenzothiophenes via electrochemical-oxidation promoted difunctionalization of active alkyne has been developed. In this protocol, inexpensive and easily available potassium thiocyanate was chosen as the thiocyanation reagent, 2-alkynylthioanisoles as the substrates, a variety of 3-thiocyanatobenzothiophenes were obtained in moderate to good yields under oxidant- and catalyst-free conditions. Moreover, the continuous flow system has good applicability for this transformation, the use of continuous flow system has overcome the disadvantage of low efficiency in traditional electrochemical amplification, and realized the stable and excellent yields of target products in the scale-up reactions.

Predicting nanoemulsion formulation and studying the synergism mechanism between surfactant and cosurfactant: A combined computational and experimental approach.

Nanoemulsion (NE) is a dosage form widely used in pharmaceutical, food, agrochemical, cosmetics, and personal care industries. NE systems are usually formulated through trial and error via numerous semi-empirical experiments. Moreover, the complex interaction mechanisms between the formulation surfactant and cosurfactant are difficult to understand. Dissipative particle dynamics (DPD) may be helpful in solving these formulation problems. Silibinin is a flavonolignan isolated from milk thistle, which has demonstrated antioxidant and antimicrobial effects. For this project, silibinin-loaded nanoemulsion (SBNE) was formulated by DPD, including surfactant and cosurfactant screening, pseudo-ternary phase construction, and SBNE characterization, all of which were verified by experimentation. Most importantly, this work shows that DPD can be adopted to explore the synergetic mechanisms between the surfactant and cosurfactant, including emulsification efficiency, distance, angle, arrangement, and order parameter. Additional verification experiments on the antioxidant and antimicrobial applications of simulation-designed SBNE were also carried out and confirmed DPD-predicted results. As such, predicting NE formulation by DPD has been proven to be feasible. For SBNE, the addition of PEG400 cosurfactant stretches the Cremophor RH40 surfactant molecules and assists in a more orderly arrangement. An enhanced interfacial thickness in SBNE could be attributed to the stretched hydrophilic head group and the decreased angle between the molecular axis and interface normal. These DPD and experimentally-verified results indicated that a proper cosurfactant will enhance the interfacial thickness, decrease the consumption of surfactant, and benefit NE formation. This new computationally applied knowledge should facilitate optimizing, designing, and understanding NE formulation more rationally and scientifically.

Cu(i)-Catalyzed asymmetric intramolecular addition of aryl pinacolboronic esters to unactivated ketones: enantioselective synthesis of 2,3-dihydrobenzofuran-3-ol derivatives.

An (S,S)-QuinoxP*-supported Cu(i) catalyst has been disclosed for highly enantioselective intramolecular addition of aryl pinacolboronic esters to unactivated ketones under mild reaction conditions. This protocol showcases a broad substrate tolerance and allows access to various chiral 2,3-dihydrobenzofuran-3-ol derivatives in generally good yields with excellent enantioselectivities.

Phosphine-Catalyzed Asymmetric (3 + 2) Annulations of δ-Acetoxy Allenoates with ß-Carbonyl Amides: Enantioselective Synthesis of Spirocyclic ß-Keto γ-Lactams.

While the phosphine catalysis is a powerful tool for the construction of N-heterocycles, the phosphine-catalyzed annulations toward lactam motif are still extremely scarce. Here, we report the asymmetric (3 + 2) annulations of δ-acetoxy allenoates with ß-carbonyl amides by using the (R)-SITCP catalyst. The δC and γC of allenoate respectively engage in annulation with the αC and N of the amide, forging a γ-lactam with good to excellent stereoselectivity.

Construction of polycyclic frameworks via a DMAP-catalysed tandem addition-(4 + 2) annulation sequence of δ-acetoxy allenoate.

Here is reported the DMAP-catalyzed addition/(4 + 2) annulation domino reaction of δ-acetoxy allenoate with either salicylaldehyde-derived oxadiene or pyrrolealdehyde-derived oxadiene, which provides a facile method toward polycyclic frameworks. A cationic intermediate, 3-ammonium-2,4-dienoate, is proposed to be involved via an addition-elimination process between an allenoate and a catalyst, which is capable of undergoing addition with either O- or N-nucleophile and subsequent (4 + 2) annulation with oxadiene.

Enantioselective construction of quaternary tetrahydropyridines by palladium-catalyzed vinylborylation of alkenes.

Here, the highly enantioselective construction of 3,3-disubstituted tetrahydropyridines via Pd(0)-catalyzed asymmetric vinylborylation of (Z)-1-iodo-dienes and B2pin2 in the presence of a (S)-p-CF3-BnPHOX ligand is reported. This process is supposed to be initiated by oxidative addition of Pd(0) to vinyl iodide, followed by transmetallation with B2pin2, insertion of the pendant alkene and reductive elimination of alkyl-Pd(ii)-Bpin.

Enantioselective Synthesis of 4H-Pyran via Amine-Catalyzed Formal (3 + 3) Annulation of δ-Acetoxy Allenoate.

The formal (3 + 3) annulations of δ-acetoxy allenoates and 1C,3O-bisnucleophiles are reported with the use of 6'-deoxy-6'-perfluorobenzamido-quinine (4g) as a catalyst, which provide rapid access to 4H-pyrans with excellent enantioselectivity. The reaction features a wide reaction scope and mild reaction conditions. The crucial roles of amide NH of 4g as a H-bond donor have also been elucidated, which not only activates allenoate to facilitate formation of cationic intermediate A but also enhances the electrophilicity of its δ-position for nucleophilic 1,6-addition.

Access to thiopyrano[2,3-b]indole via tertiary amine-catalyzed formal (3+3) annulations of ß'-acetoxy allenoates with indoline-2-thiones.

DABCO-catalyzed formal (3+3) annulations of ß'-acetoxy allenoates with indoline-2-thiones are described, which provide facile access to thiopyrano[2,3-b]indole under mild reaction conditions. The reaction might proceed via the SN2'-SN2'-type process between ß'-acetoxy allenoate and indole-2-thiolate with the assistance of the DABCO catalyst and K2CO3 additive, followed by intramolecular Friedel-Crafts reaction at the 3-position of indole and central carbon of allene.

Amine-Catalyzed Asymmetric (3 + 3) Annulations of ß'-Acetoxy Allenoates: Enantioselective Synthesis of 4H-Pyrans.

The asymmetric (3 + 3) annulations of ß'-acetoxy allenoates with either 3-oxo-nitriles or pyrazolones have been realized by using 6'-deoxy-6'-[(l)-N,N-(2,2'-oxidiethyl)-valine amido]quinine (6h) as the catalyst. The three functions of catalyst 6h, including Lewis base (quinuclidine N), H-bond donor (amide NH), and Brønsted base (morpholine N), cooperatively take crucial roles on the chemo- and enantioselectivity, allowing for the construction of 4H-pyran and 4H-pyrano[2,3-c]pyrazole in high yields and enantioselectivity.

Access to Thiophene and 1H-Pyrrole via Amine-Initiated (3 + 2) Annulation and Aromatization Cascade Reaction of ß'-Acetoxy Allenoate and 1,2-Bisnucleophile.

The amine-catalyzed cascade (3 + 2) annulation and aromatization sequence between ß'-acetoxy allenoates and 1,2-bisnucleophiles has been developed. When 1,4-dithane-2,5-diol is used as the bisnucleophile partner, the corresponding reaction affords fully substituted thiophene-2-carbaldehyde, which might proceed via the amine-catalyzed (3 + 2) annulation and subsequent oxidative aromatization. The reaction protocol is also applicable to a 2-tosylamino-carbonyl bisnucleophile, wherein the (3 + 2) annulation is followed by 1,2-elimination of a tosyl group and isomerization to give a 1H-pyrrole product.

Phosphine-Catalyzed Addition/Cycloaddition Domino Reactions of ß'-Acetoxy Allenoate: Highly Stereoselective Access to 2-Oxabicyclo[3.3.1]nonane and Cyclopenta[a]pyrrolizine.

Two classes of phosphine-catalyzed addition/cycloaddition domino reactions of ß'-acetoxy allenoate 1 have been developed. The reaction of 1 with 2-acyl-3-methyl-acrylonitrile 2 readily occurs to give 2-oxabicyclo[3.3.1]nonane 3, furnishing the ß'-addition/[4 + 4] cycloaddition domino sequence. In this sequence, ß'C of allenoate 1 is an electrophilic center, and its ß'C and γC serve as a 1,4-dipole. When the other reaction partner is switched to 2-acyl-3-(2-pyrrole)-acrylonitrile 8, a γ-addition/[3 + 2] cycloaddition domino reaction is instead observed, in which allenoate 1 exhibits dual electrophilic reactivity of γC and 1,3-dipole chemical behavior of ßC and ß'C. Furthermore, both of these two asymmetric variants have also been achieved with up to 93% ee. The domino reactions presented in this report are valuable for highly stereoselective construction of complex structures under mild reaction conditions.