Iridium-Catalyzed Double Convergent 1,3-Rearrangement/Hydrogenation of Allylic Alcohols.

Enantioconvergent catalysis has the potential to convert different isomers of a starting material to a single highly enantioenriched product. Here we report a novel enantioselective double convergent 1,3-rearrangement/hydrogenation of allylic alcohols using an Ir-N,P catalyst. A variety of allylic alcohols, each consisting of a 1:1:1:1 mixture of four isomers, were converted to the corresponding tertiary alcohols with two contiguous stereogenic centers, in up to 99% ee and 99:1 d.r. DFT calculations, and control experiments suggest that the 1,3-rearrangement is the crucial stereodetermining element of the reaction.

Circular RNA Paired-Related Homeobox 1 Promotes Gastric Carcinoma Cell Progression via Regulating MicroRNA-665/YWHAZ Axis.

BACKGROUND: Gastric carcinoma (GC) is a ubiquitous malignant tumor worldwide. Circular RNA paired-related homeobox 1 (circ-PRRX1), one kind of non-coding RNAs, has been reported to act as a promoter in tumor growth. This study aims to explore the effects of circ-PRRX1 on proliferation, apoptosis, and metastasis in GC and the underlying regulatory mechanisms. METHODS: The expression of circ-PRRX1, miR-665, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze YWHAZ protein expression. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-Htetrazolium bromide (MTT), flow cytometry, and transwell assay were carried out to assess the viability, apoptosis, migration, and invasion in GC cells. The interaction between miR-665 and circ-PRRX1 or YWHAZ was predicted by StarBase v2.0 and identified by dual-luciferase reporter system. Xenograft mouse model was employed to determine the effects of circ-PRRX1 knockdown on GC growth in vivo. RESULTS: Compared with normal tissues and cells, circ-PRRX1 and YWHAZ levels were upregulated, and miR-665 was downregulated in GC tissues and cells. Functionally, circ-PRRX1 knockdown inhibited the viability, migration, and invasion and promoted apoptosis in GC cells, whereas anti-miR-665 abolished these effects. Mechanistically, circ-PRRX1 was confirmed as a sponge of miR-665 to regulate YWHAZ expression. Xenograft mouse model suggested that circ-PRRX1 knockdown reduced GC cells growth in vivo. CONCLUSION: Circ-PRRX1 knockdown suppressed GC development by targeting miR-665 to inhibit YWHAZ expression, and the potential molecular mechanism may provide a theoretical basis for GC therapy.

Access to Polysubstituted (Furyl)methylthioethers via a Base-Promoted S-H Insertion Reaction of Conjugated Enynones.

A convenient and applicable approach to the construction of diverse functionalized (2-furyl)methylthioether derivatives via base-promoted S-H insertion of conjugated enynones with thiophenols or thiols has been developed. This reaction features readily available starting materials, high atom economy, broad substrate scope, and versatile operation. Moreover, the synthetic utility of this method has been demonstrated by the efficient synthesis of the CNKSPR1 inhibitor precursor and late-stage functionalization of glutathione.

Assembly of Polysubstituted Maleimides via Palladium-Catalyzed Cyclization Reaction of Alkynes with Isocyanides.

An efficient and convenient palladium-catalyzed cyclization reaction of alkynes with isocyanides is described herein. This protocol allows the practical synthesis of many valuable polysubstituted maleimide derivatives after hydrolysis with a broad scope of substrates and mild reaction conditions. C-C, C═O, and C-N bonds were constructed in this transformation with isocyanide serving as both C and N sources.

Mild and efficient synthesis of benzothiazolopyrimidine derivatives via CuAAC/ring cleavage/cyclization reaction.

An operationally mild and efficient synthesis of benzothiazolopyrimidine is achieved by a three-component reaction of 2-aminebenzo[d]thiazoles, sulfonyl azides and terminal ynones. This cascade process involved a CuAAC/ring cleavage/cyclization reaction. Particularly, most of the benzothiazolopyrimidine derivatives could be isolated by filtration without further purification.

Radical-based functionalization-oriented construction: rapid assembly of azaarene-substituted highly functionalized pyrroles.

Totally different functionalization and construction as two fundamental synthetic protocols have long been applied to furnish azaarene variants. Here, a novel radical-based functionalization-oriented construction strategy by exploiting the electronic properties of azaarenes and the high reactivity of radicals is developed. Under a photoredox catalysis platform, the robust ability of such an artful combination of functionalization with construction is disclosed in the synthesis of valuable 3-azaarene-substituted densely functionalized pyrroles. In addition to the ability to use the readily accessible feedstocks, the high synthetic efficiency and the good functional group tolerance, the substrate scope is broad (81 examples) resulting from the capability to flexibly replace the types of azaarenes and other substituents. Control experiments and density functional theory (DFT) calculations elucidate the plausible mechanism involving the reaction pathways and the important role of NaH2PO4 as an additive in the reaction.

Palladium-catalyzed primary amine-directed regioselective mono- and di-alkynylation of biaryl-2-amines.

The first example of the palladium-catalyzed primary amine-directed C(sp2)-H alkynylation of biaryl-2-amines has been developed by using (bromoethynyl)triisopropylsilane as an alkynylating reagent. This protocol exhibits a broad substrate scope, excellent regioselectivity and gram-scale synthesis. Significantly, the versatility of this straightforward method was further demonstrated by controlled mono- and di-alkynylation.

Synthesis of 2,3-Difunctionalized Benzofuran Derivatives through Palladium-Catalyzed Double Isocyanide Insertion Reaction.

A novel palladium-catalyzed tandem cyclization of 1-(allyloxy)-2-ethynylbenzene derivatives with isocyanides in the presence of water has been developed. The key intermediates, benzofuran-3-α-carbonyl aldehydes, were obtained through a simple acid hydrolysis process and could serve as precursors for structurally diverse 2,3-difunctionalized benzofuran derivatives such as important 2-benzofurylquinoxalines, benzofuran-3-α-ketoesters and benzofuryl ynediones. This transformation features convenient operation, simple and commercially available starting materials, broad functional-group compatibility, and moderate to good reaction yields.

Tandem cyclization of o-alkynylanilines with isocyanides triggered by intramolecular nucleopalladation: access to heterocyclic fused 2-aminoquinolines.

Herein, a novel strategy for the synthesis of various heterocyclic fused 2-aminoquinolines via palladium-catalyzed tandem cyclization of o-alkynylanilines with isocyanides has been developed. This process includes trans-oxy/aminopalladation, isocyanide insertion, elimination and 1,3-hydrogen migration. Besides high atom and step economy, this method shows good functional group compatibility with excellent chemo- and regioselectivities under mild reaction conditions.

Palladium-Catalyzed Cyclization of N-Acyl- o-alkynylanilines with Isocyanides Involving a 1,3-Acyl Migration: Rapid Access to Functionalized 2-Aminoquinolines.

A simple and expedient approach for the synthesis of functionalized 2-aminoquinolines via palladium-catalyzed annulation of N-acyl- o-alkynylanilines with isocyanides has been developed with high atom economy, in which an unconventional 6- endo-dig cyclization process is observed. Further investigations of the mechanism demonstrated that an intramolecular acyl migration of the N-protecting groups was involved in this transformation.

Dual Role of H2O2 in Palladium-Catalyzed Dioxygenation of Terminal Alkenes.

A palladium-catalyzed, environmentally friendly dioxygenation reaction of simple alkenes has been developed that enabled rapid assembly of valuable α-hydroxy ketones with high atom economy. Notably, control experiments and 18O isotope-labeling experiments established that H2O2 played a dominant dual role in this transformation.

Palladium-Catalyzed Redox-Neutral N-O/C(sp3)-H Functionalization of Aryl Oximes with Isocyanides.

A redox-neutral palladium-catalyzed N-O/C(sp3)-H functionalization of aryl oximes with isocyanides has been developed. Various pyrrole derivatives were prepared in good to excellent yields through oxime carbamate as a key intermediate and internal oxidant in this process. Furthermore, this transformation also features readily available starting materials, good functional group tolerance, and excellent regioselectivity.

Csp(3)-P versus Csp(2)-P Bond Formation: Catalyst-Controlled Highly Regioselective Tandem Reaction of Ene-Yne-Ketones with H-Phosphonates.

Under copper-catalyzed or base-promoted conditions, a wide range of ene-yne-ketones react with H-phosphonates to afford various phosphorylated furans in good yields. A copper carbene generation or a Michael addition is proposed as the key step in the selective construction of the Csp(3)-P or Csp(2)-P bond, which is supported by carbene capture reactions and interval (31)P NMR experiments. Furthermore, this method features inexpensive metal catalysts, no usage of oxidant, and high atom economy, which make it attractive and practical.

Palladium-Catalyzed Multicomponent Reaction (MCR) of Propargylic Carbonates with Isocyanides.

A palladium-catalyzed multicomponent reaction (MCR) of propargylic carbonates with isocyanides is reported. Remarkably, the orderly insertion of isocyanides affords two types of valuable N-heterocyclic products (Z)-6-imino-4,6-dihydro-1H-furo[3,4-b]pyrrol-2-amines and (E)-5-iminopyrrolones in high yields. Systematic analysis of the reaction conditions indicates that the selectivity of these N-heterocyclic products can be controlled by ligands and temperature.

Palladium-catalyzed Csp(2)-H carbonylation of aromatic oximes: selective access to benzo[d][1,2]oxazin-1-ones and 3-methyleneisoindolin-1-ones.

A highly selective palladium-catalyzed carbonylation of Csp(2)-H bonds with aromatic oximes for the synthesis of benzo[d][1,2]oxazin-1-ones and 3-methyleneisoindolin-1-ones has been developed. Interestingly, we found that the N-OH group of the oximes could be used as a directing group and/or an internal oxidant under different conditions. This transformation is supposed to proceed through a hydroxyl-directed ortho-Csp(2)-H carbonylation or activation of vinyl Csp(2)-H bond/ortho-Csp(2)-H carbonylation process. The uses of readily available starting materials, atmospheric pressure of carbon monoxide, as well as operational simplicity make this practical and atom-economical method particularly attractive.

Diagnostic difficulties and treatment strategy of hepatic angiomyolipoma.

OBJECTIVE: Based on a large series of histopathologically confirmed hepatic angiomyolipomas, we retrospectively studied the typical diagnostic features of hepatic angiomyolipoma and proposed a treatment strategy for this disease. MATERIALS AND METHODS: From December 1997 to December 2007, 74 consecutive patients who received definitive treatment for hepatic angiomyolipoma, at a single tertiary center, were studied. RESULTS: There was a marked female predominance (54 females vs. 20 males) and the mean age was 42 years. Forty patients had no symptoms and the tumors were detected incidentally during a medical check-up. From this study, we proposed the typical diagnostic features of hepatic angiomyolipoma to be the absence of risk factors for malignancy, normal tumor marker levels, and typical imaging features on ultrasound (USG), abdominal contrast computed tomography (CT), or magnetic resonance imaging (MRI). Only 23% of patients could have been diagnosed before surgery using these features. One patient (1.4%) had a malignant angiomyolipoma, and died with distant metastases 14 months after surgery. After a median follow-up of 64 months, there was no recurrence in the other 73 patients. CONCLUSION: Patients with typical diagnostic features suggestive of hepatic angiomyolipoma could be observed with regular surveillance. Definitive treatment should be performed when the tumor has symptoms/complications, when the tumor is enlarging, or when a malignant lesion cannot be ruled out.