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The question whether interference with the ubiquitous splicing machinery can lead to cell-type specific perturbation of cellular function is addressed here by T cell specific ablation of the general U5 snRNP assembly factor CD2BP2/U5–52K. This protein defines the family of nuclear GYF domain containing proteins that are ubiquitously expressed in eukaryotes with essential functions ascribed to early embryogenesis and organ function. Abrogating CD2BP2/U5–52K in T cells, allows us to delineate the consequences of splicing machinery interferences for T cell development and function. Increased T cell lymphopenia and T cell death are observed upon depletion of CD2BP2/U5–52K. A substantial increase in exon skipping coincides with the observed defect in the proliferation/differentiation balance in the absence of CD2BP2/U5–52K. Prominently, skipping of exon 7 in Mdm4 is observed, coinciding with upregulation of pro-apoptotic gene expression profiles upon CD2BP2/U5–52K depletion. Furthermore, we observe enhanced sensitivity of naïve T cells compared to memory T cells to changes in CD2BP2/U5–52K levels, indicating that depletion of this general splicing factor leads to modulation of T cell homeostasis. Given the recent structural characterization of the U5 snRNP and the crosslinking mass spectrometry data given here, design of inhibitors of the U5 snRNP conceivably offers new ways to manipulate T cell function in settings of disease.

An unusual spiroannulation/cycloisomerization cascade of 3-(2-ethynylaryl)- N -tosylaziridines with indoles enabled by cooperative gold/scandium catalysis is presented, which facilitates the synthesis of 5 H -benzo[ b ]carbazoles in moderate to excellent yields. This protocol features a broad substrate scope and good functional-group compatibility. Additionally, the resulting 5 H -benzo[ b ]carbazoles exhibit good fluorescence properties, demonstrating the synthetic practicality of this method. Moreover, control experiments were performed to illustrate the reaction mechanism.

Introduction: We investigated the frequency of uveitic macular edema (UME) in patients with different types of noninfectious uveitis and present the primary treatment methods for UME at a specialized eye center in Shaanxi Province, China., Methods: We conducted a retrospective, noninterventional, observational survey involving 1946 patients with noninfectious uveitis (2816 eyes). The collected data included sex, age of uveitis onset, age of UME onset, anatomical classification of uveitis, and the treatment administered to UME patients., Results: Of the 1946 patients with noninfectious uveitis, 929 (47.74%) were male and 1017 (52.26%) were female. The average age of all participants in the study was 42.19 ± 15.34 years, with average age at uveitis onset of 39.50 ± 15.52 years. Among the patients, 1003 (51.54%), 239 (12.28%), 410 (21.07%), and 294 (15.11%) had anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis, respectively. UME was observed in 134 (6.89%) of the uveitis patients. The average age of UME patients was 47.33 ± 17.17 years, with average age at uveitis onset of 45.78 ± 17.20 years. Out of the 134 UME patients, 3 (0.30%), 15 (6.28%), 47 (11.46%), and 69 (23.47%) had anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis, respectively. Among them, 37 were lost to follow-up, 44 received adalimumab (ADA) combined with low-dose prednisone and with or without conventional immunosuppressants, 19 received interferon-α2a therapy, 14 received intravitreal corticosteroid injections (such as dexamethasone implant or fluocinolone acetonide), 11 received low-dose corticosteroids combined with conventional immunosuppressants, 5 received only oral prednisone, and 4 received repeated peribulbar or subconjunctival injections of triamcinolone acetonide., Conclusions: At our tertiary ophthalmic center in Shaanxi Province, China, only 6.89% of patients with noninfectious uveitis were diagnosed with UME. The primary treatment modality for UME in our center is ADA, in accordance with treatment guidelines and the Chinese medical insurance reimbursement system., (© 2023. The Author(s).)

A palladium-catalyzed ring-opening [3 + 2]-annulation of spirovinylcyclopropanyl oxindoles with seven-membered cyclic N -sulfonylimines has been developed. A wide range of seven-membered benzosultams featuring both a quaternary center and axially chiral biaryl scaffolds have been afforded in an average yield of 87% with moderate to excellent diastereoselectivities. The enantioenriched benzosultams were also accessed successfully in good yields with excellent atropoenantioselectivities enabled by the Pd 2 (dba) 3 /( S , S , S )-SKP ligand. The practical utility of this protocol was further demonstrated by the gram-scale reaction and diversified synthetic transformations of the desired seven-membered benzosultam.

The introduction of selenium-containing functional groups into steroids to study the biological activities of related derivatives is rarely reported in the literature. In the present study, using cholesterol as raw material, four cholesterol-3-selenocyanoates and eight B-norcholesterol selenocyanate derivatives were synthesized, respectively. The structures of the compounds were characterized by NMR and MS. The results of the in vitro antiproliferative activity test showed that the cholesterol-3-selenocyanoate derivatives did not exhibit obvious inhibitory on the tested tumor cell lines. However, the B-norcholesterol selenocyanate derivatives obtained by structural modification of cholesterol showed good inhibitory activity against the proliferation of tumor cell. Among them, compounds 9b-c, 9f and 12 showed similar inhibitory activity against tested tumor cells as positive control 2-methoxyestradiol, and better than Abiraterone. At the same time, these B-norcholesterol selenocyanate derivatives displayed a strong selective inhibitory against Sk-Ov-3 cell line. Except for compound 9g, the IC 50 value of all B-norcholesterol selenocyanate compounds against Sk-Ov-3 cells was less than 10 µM, and compound 9d was 3.4 µM. In addition, Annexin V-FITC/PI double staining was used to analyze the cell death mechanism. The results showed that compound 9c could induce Sk-Ov-3 cells to enter programmed apoptosis in a dose-dependent manner. Furthermore, the in vivo antitumor experiments of compound 9f against zebrafish xenograft tumor showed that 9f displayed obvious inhibitory effect on the growth of human cervical cancer (HeLa) xenograft tumor in zebrafish. Our results provide new thinking for the study of such compounds as new antitumor drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Although growing studies have reported the disturbances of trace elements (TEs) homeostasis was closely associated with the occurrence of colorectal cancer (CRC), the clinical value of TEs in CRC with different molecular subtypes was largely unknown. This study aimed to explore the correlation between KRAS mutations/MSI status and serum TEs levels in patients with CRC. Methods: The serum concentrations of 18 TEs were detected by inductively coupled plasma emission spectrometry (ICP-MS). MSI status (two mononucleotides: BAT25, BAT26, three dinucleotides: D2S123, D5S346, and D17S250), KRAS (G516T, G517A, G518C, G520T, G521A, G522C, and G532A) mutations were detected by the multiplex fluorescent PCR and the real-time fluorescent quantitative PCR, respectively. The correlations among KRAS mutations/MSI status, demographic and clinical characteristics, and TEs were analyzed by Spearman correlation analysis. Results: The propensity score matching (PSM) analysis was adopted to minimize differences between groups. Before PSM, 204 CRC patients were recruited in this study, including 123 KRAS -negative patients and 81 KRAS -positive patients according to the test results of KRAS mutations, and 165 MSS patients and 39 MSI patients based on MSI detection. After PSM, the serum concentration of Mn was significantly lower in CRC patients with KRAS mutations than those without KRAS mutations, and a significant negative correlation was observed between Mn and Pb in the KRAS -positive cases. CRC patients carrying MSI had a significantly lower level of Rb compared to MSS patients. Importantly, Rb was significantly positively correlated with Fe, Mn, Se, and Zn in patients with MSI. Collectively, all our data indicated that the occurrence of different molecular events might be accompanied by different alterations in types and levels of serum TEs. Conclusions: CRC patients with different molecular subtypes presented different alterations in types and levels of serum TEs. Mn was significantly negatively correlated with the KRAS mutations, and Rb was noticeably negatively correlated with the MSI status, indicating certain TEs might contribute to the pathogenesis of molecular subtype-specific colorectal cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A visible-light-induced defluorinative dichloromethylation of α-CF 3 alkenes was developed with cheap and readily accessible chloroform simultaneously as a dichloromethylation reagent and reaction medium, leading to the facile preparation of new polyhalogenated scaffolds. Notably, the change from CHCl 3 to CDCl 3 offers a straightforward pathway for accessing the deuterated analogues with excellent degrees of D incorporation. Mechanistic studies suggested the reaction underwent a radical addition of the dichloromethyl radical with alkenes, followed by sequential single-electron transfer and defluorination. This protocol features mild conditions, easy operation, facile scalability, and high efficiency, allowing convenient access to dichloronated gem -difluoroalkenes.

Straightforward access to steroidal selenocyanates in a single assembly step from steroids remains a significant challenge. However, the development of novel method for the synthesis of steroidal selenocyanates and further investigation of their bioactivities have largely lagged behind. In this work, selenocyano groups were directly introduced into the 17- or 21-position of pregnenolone, the 2-position of estradiol, and the 16-position of estrone. A total of 16 estrogen selenocyanate derivatives with diverse structures were synthesized, and the tumor cell lines closely related to the expression level of estrogen were used to investigate the inhibitory activity of the target products on tumor cell proliferation in vitro. The results revealed that the 17-selenocyano-substituted pregnenolone selenocyanate derivatives 1b-3b exhibit obvious inhibitory activity against the tested tumor cell lines. Additionally, the 2-selenocyano-substituted estradiol derivatives and 16-selenocyano-substituted estrone derivatives exhibit selective inhibitory on HeLa cell lines. Among them, 2-selenocyano-3-methoxyestradiol-17-benzoate (7e) displayed an IC 50 value of 4.1 µM against HeLa cells and induced programmed apoptosis in HeLa cancer cells. Furthermore, compound 7e could significantly inhibit the growth of human cervical cancer xenografts in zebrafish in vivo. This approach provides new insights for future steroid antitumor drug design., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The diastereoselective assembly of spiroindolenines via a synergistic scandium/gold-catalyzed dearomative spiroannulation is herein described. This protocol offers access to a wide variety of spiroindolenine derivatives in 86% average yield with moderate to excellent diastereoselectivities (up to 97:3 dr). The control experimental studies lend support to the bimetallic relay catalysis. Moreover, the scale-up reaction and synthetic transformations of spiroindolenine product further demonstrate its synthetic utility.

An unprecedented photoredox-catalyzed phosphine-mediated deoxygenation of hexafluoroacetone hydrate was established to accomplish the hydroxylpolyfluoroalkylation of electron-deficient alkenes. A range of bis(trifluoromethyl)carbinols were facilely accessed by using readily available hexafluoroacetone hydrate, instead of toxic gaseous hexafluoroacetone. A range of electron-deficient alkenes are tolerated, giving the corresponding hydro-hydroxylpolyfluoroalkylated products in moderate to high yields. Remarkable features of this synthetic strategy include operational simplicity, mild reaction conditions, excellent regioselectivity, and broad functional group tolerance. The success of this strategy relies on the delicate utilization of aldehyde/ketone-gem-diol intrinsic equilibrium, which offers an innovated open-shell pathway for the assembly of synthetically challenging polyfluoroalkylated scaffolds., (© 2022 Wiley-VCH GmbH.)

A metal-free photosensitized protocol for regioselective diamination of alkene feedstocks over a single step was developed based on the rationally designed bifunctional diamination reagent, thus affording a range of differentially protected 1,2-diamines in moderate to high yields. Mechanistic studies reveal that the reaction is initiated with a triplet-triplet energy transfer between thioxanthone catalyst and diamination reagent, followed by fragmentation to simultaneously generate long-lived iminyl radical and transient amidyl radical. The excellent regioselectivity presumably stems from the large reactivity difference between two different N-centered radical species. This protocol is characterized by excellent regioselectivity, broad functional group tolerance, and mild reaction conditions, which would enrich the diversity and versatility of facilitate the diversity-oriented synthesis of 1,2-diamine-containing complex molecule scaffolds., (© 2022 Wiley-VCH GmbH.)

A photoredox-catalysed chlorination of quinoxalin-2(1 H )-ones was developed by using CHCl 3 as a chlorine source, thus affording various 3-chloroquinoxalin-2(1 H )-ones in moderate to high yields. This protocol is characterized by mild reaction conditions, excellent regioselectivity, and readily available chlorination agent. Considering the operational simplicity and low cost of this chlorination approach, this developed method offers an innovative pathway for rapid incorporation of chlorine functionality into heteroarenes, and will inspire broader exploitation of new chlorination strategies.

Herein, readily available and inexpensive CDCl 3 was first identified as a new trideuteromethylation reagent under photoredox-catalyzed conditions. Thus, a facile photocatalytic protocol for the C-H trideuteromethylation of quinoxalin-2(1 H )-one was achieved. This operationally straightforward transformation displays a broad scope and provides a new route to introduce the trideuteromethyl group (CD 3 ) with excellent levels of deuterium content.

Reported herein is a visible-light-induced, catalyst-free intramolecular cyclization of 4-phenylsulfonyl-2,3,5,6-tetrachloropyridine, leading to rapid assembly of a series of unprecedented benzo[4,5]thieno[3,2- c ]pyridine 5,5-dioxide scaffolds under mild conditions. The rational introduction of a perchloropyridin-4-yl module significantly facilitated this photoinduced process and offers a versatile platform for broad structural variation. Mechanistic studies revealed that a newly identified charge-transfer complex with carbonate is crucial to this photoinduced process.

A highly modular 1,4-difunctionalization of 1,3-dienes with bromodifluoroacetamides and sulfinates/amines through a photoinduced palladium-catalyzed radical relay process is described herein. This developed protocol offers a facile and general route to access a variety of value-added CF 2 -incorporated alkenes in moderate to good yields. The versatility and flexibility of this approach have been well illustrated by readily accessible starting materials, synthetic convenience, and wide functional group compatibility.

Reported herein is a photoredox-catalyzed amination of o- hydroxyarylenaminones with tert -butyl ((perfluoropyridin-4-yl)oxy)carbamate, a versatile amidyl-radical precursor developed in our laboratory. This work establishes a new cascade pathway for the assembly of a range of 3-aminochromones under mild conditions. Downstream transformations of the obtained 3-aminochromones to construct diverse amino pyrimidines greatly broaden the applications of this photocatalyzed protocol.

A catalyst-free strategy for regioselective hydroxydifluoroalkylation of alkenes with alkyl bromides was developed, affording a series of difluoroalkylated tertiary alcohols in moderate to good yields. This photocatalyst-free protocol shows broad substrate scope under mild conditions. Moreover, mechanistic studies revealed that a newly identified electron donor-acceptor complex is crucial to this transformation.

Regiodivergent formal [5+2]- and [4+2]-annulation reactions of indole derivatives with 2-(2-alkynyl)aryl cyclopropane-1,1-diesters (ACPs) have been developed. A series of tetracyclic indole derivatives were delivered in a 77% average yield with excellent regioselectivities enabled by Au(I)/Sc(III) bimetallic relay catalysis. A gram-scale reaction and further transformation of the resulting tetracyclic indoles demonstrated the practical utility of this protocol. Moreover, the photophysical properties of the obtained multicyclic compounds were also investigated.

A visible light-promoted radical relay of N -allylbromodifluoroacetamide with quinoxalin-2(1 H )-ones was developed in which 5- exo - trig cyclization and C-C bond formation were involved. This protocol was performed under mild conditions to facilely offer a variety of hybrid molecules bearing both quinoxalin-2(1 H )-one and 3,3-difluoro-γ-lactam motifs. These prepared novel skeletons would expand the accessible chemical space for structurally complex heterocycles with potential biological activities.

Divergent synthesis provides an indispensable route to rapid acquisition of structurally diverse chemical scaffolds from identical starting materials. Herein, we describe unprecedented divergent annulations of o -hydroxyarylenaminones promoted by tert -butyl nitrite (TBN) under mild conditions. Two different types of benzo- oxa -heterocycle, including oximinochromanones and oximinocoumaranones, were smoothly assembled with a broad substrate scope and good functional group compatibility.

The global rise of antibiotic resistance of pathogenic bacteria has become an increasing medical and public concern, which is further urging the development of antimicrobial channels for treating infectious diseases. The combination of photodynamic therapy (PDT) with photothermal therapy (PTT) has been considered as a promising alternative way for the replacement of traditional antibiotic therapy. In this research, the newly fabricated Chlorin-e6 (Ce6) conjugated mesoporous silica-coated AuNRs, designated AuNR@SiO 2 -NH 2 -Ce6, exhibited synergistic photothermal effects and single oxygen localized generation property, and showed stronger photoinactivation for bacteria compared with Ce6. AuNR@SiO 2 -NH 2 -Ce6 can anchor to the cell membrane and accumulate in the interior of cells. Furthermore, the unique porous structure of AuNR@SiO 2 NH 2 enabled Ce6 encapsulation in the mesopores and was subsequently released and activated by photothermic effect, allowing the generated single oxygen to penetrate into the cytoplasmic membrane or directly enter the interior of bacteria cells, thus overcoming the inherent defects of single oxygen. AuNR@SiO 2 -NH 2 -Ce6 not only damaged the integrity of the cell membrane of bacteria but also facilitated the cellular permeation and accumulation of external nanoagents in the bacteria upon light irradiation. In addition, AuNR@SiO 2 -NH 2 -Ce6 exhibited negligible cytotoxicity toward mammalian cells and hemolytic activity. Therefore, AuNR@SiO 2 -NH 2 -Ce6 may be highly promising candidates as topical antibacterial agents, and this study has wide implications on the design of next-generation antimicrobial agents.

An unprecedented electrochemical heterodifunctionalization of α-CF 3 alkenes with benzenesulfonyl hydrazides was accomplished in this work, wherein a β-sulfonyl and a α-hydroxyl group were simultaneously incorporated across the olefinic double bond in a single operation. Consequently, a series of potentially medicinally valuable and densely functionalized α-trifluoromethyl-β-sulfonyl tertiary alcohols were assembled under mild conditions. Electrochemically-driven oxidative 1,2-difunctionlization of electron-deficient alkenes well obviates the need for oxidizing reagents, thus rendering this protocol more eco-friendly.

The unexpected gold-catalyzed formal [3+2]-cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with 2-(1-Alkynyl)-2-alken-1-ones is reported. Both diastereomers of the corresponding cycloadducts were formed in moderate to excellent yields with excellent diastereoselectivities by switching the catalytic system from mono-gold to gold/silver bimetallic catalytic system. The practicality of this protocol is demonstrated by scale-up reaction and the transformations of the cycloadduct., (© 2021 Wiley-VCH GmbH.)

A novel phosphine-catalysed, one-pot domino approach for the annulation of 2-formylphenyl alkynoates with activated methylene compounds to construct various cyclopentene-fused dihydrocoumarins is reported. This developed strategy provides a facile and efficient approach for the synthesis of structurally complex coumarins from inexpensive and readily available alkynoates.

Reported herein is a visible-light-induced sulfonation of α-trifluoromethylstyrenes with sodium sulfinates, which provides a series of α-trifluoromethyl-β-sulfonyl tertiary alcohols. This new synthetic protocol is enabled by a charge-transfer complex between oxygen and sulfinates, featuring broad substrate scope and scalability. Excellent functional group compatibility and chemoselectivity render this method suitable for sulfonation of pharmaceutically relevant molecules. In the presence of D 2 O, deuteriotrifluorinated products were also obtained, further demonstrating the flexibility and synthetic potentials of this strategy.

Background: Anastomotic leakage is one of the most serious postoperative complications of rectal cancer. Prophylactic ileostomy has been widely used to reduce the risk and severity of complications of anastomotic leakage. However, prophylactic ileostomy itself has some complications, and ileostomy high output syndrome (HOS) is one of them. This study was performed to explore the risk factors of HOS in ileostomy., Methods: A total of 114 patients with HOS were screened out from 494 eligible ileostomy patients in the last 5 years. The relationship between HOS and the clinicopathological data was analyzed using the Chi-square test and Fisher's exact probability. Multivariate analysis was performed by logistic regression., Results: The incidence of HOS was 23.07% in this study. Dehydration was the most common symptom of HOS (37.7%). There was no clear correlation between HOS occurrence with sex, age, gross typing, histological grade, tumor location, lymph node metastasis, and TNM stage (p > 0.05). The incidence of HOS was 14/18 in inflammatory bowel disease patients, 18/28 in diabetes mellitus patients, and 23/72 in neoadjuvant chemoradiotherapy patients, 13/17 in total colectomy and abdominal infection patients. Multivariate analysis showed that they are risk factors for HOS (p < 0.05)., Conclusion: HOS occurred occasionally but rarely studied and lacks attention. Inflammatory bowel disease, diabetes mellitus, neoadjuvant radiotherapy chemotherapy, total colectomy and abdominal infection are the risk factors for HOS.

We herein report an unprecedented photoinduced cyclization/defluorination domino process of N -allylbromodifluoroacetamide with cyclic secondary amines. Consequently, a wide array of valuable 3-fluoro-1,5-dihydro-2 H -pyrrol-2-ones were facilely prepared from readily available starting materials under mild conditions. Preliminary mechanistic investigations suggest that a radical chain propagation and amine-promoted defluorination pathway are presumably involved in this transformation.

An enantioselective ring-opening formal [3+2]-cycloaddition of spirovinylcyclopropyl oxindoles with enals via synergistic catalysis of palladium(0) and a chiral organocatalyst has been developed, affording spirooxindoles bearing four contiguous stereocenters in good yields with excellent enantioselectivities. The generality and utility of the protocol were also demonstrated through scale-up experiments and synthetic transformation of the resulting cycloadduct.

Reported herein is the design and synthesis of new O -perhalopyridin-4-yl hydroxylamines as shelf-stable and versatile amidyl-radical precursors. The novel amination reagents can be easily prepared via a single synthetic step from inexpensive commercially available starting materials using monoprotected HONH 2 as amino source. The synthetic potency of the developed reagents was well demonstrated by direct amination of a series of quinoxalin-2(1 H )-ones and their analogues under photocatalytic conditions, even without any additive and photocatalysts.

An organocatalyzed enantiodivergent synthesis of a multifunctionalized spirooxindole-norcamphor scaffold via a [4 + 2]-annulation between cyclic α, β -unsaturated ketone and methylene indolinones has been established. The presence of CaCl 2 in DMF could reverse the enantioselectivity to facilely deliver the enantiomers of the corresponding spirooxindoles. Both enantiomers of the corresponding spirooxindoles were obtained in excellent yield and diastereo-/enantioselectivity by employing one single prolinosulfonamide catalyst.

Chromanone is a privileged structure with a wide range of unique biological activities. A phosphine-promoted, three-component domino sequence of salicylaldehyde with but-3-yn-2-one was well designed for the construction of the chromanone skeleton under mild conditions. As a consequence, a series of novel chromanone analogues bearing an all-carbon quaternary center were facilely assembled from commercially available starting materials with moderate to good yields, which hold promising applications in pharmacological studies. Mechanistic experiments were conducted to confirm the proposed mechanism.

A photoinduced SET process enables the direct B-H bond activation of NHC-boranes. In contrast to common hydrogen atom transfer (HAT) strategies, this photoinduced reaction simply takes advantage of the beneficial redox potentials of NHC-boranes, thus obviating the need for extra radical initiators. The resulting NHC-boryl radical was used for the borylation of a wide range of α-trifluoromethylalkenes and alkenes with diverse electronic and structural features, providing facile access to highly functionalized borylated molecules. Labeling and photoquenching experiments provide insight into the mechanism of this photoinduced SET pathway., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A visible-light-induced, catalyst-free radical cross-coupling cyclization of diselenides or disulfides with N -allylbromodifluoroacetamide has been developed. This developed protocol exhibits good functional group tolerance and affords a variety of 4-thio- and 4-seleno-substituted 3,3-difluoro-γ-lactams in moderate to good yields. Based on control experiments, a plausible radical-radical cross-coupling pathway is proposed.

The first photoredox-catalyzed defluoroborylation of polyfluoroarenes with NHC-BH 3 has been facilely achieved at room temperature via a single-electron-transfer (SET)/radical addition pathway. This new strategy makes full use of the advantage of photoredox catalysis to generate the key boryl radical via direct activation of a B-H bond. Good functional group tolerance and high regioselectivity offer this protocol incomparable advantages in preparing a wide array of valuable polyfluoroarylboron compounds. Moreover, both computational and experimental studies were performed to illustrate the reaction mechanism.

We herein report a phosphine-mediated domino process of MBH-type reaction/umpolung γ-addition through the rational integration of the privileged reactivities of alkynoate. Simply by manipulating the nucleophilic reagent, the developed protocol offers a facile, diversity-oriented construction of a wide range of three-substituted coumarins.

A general and straightforward protocol for di-/perfluoroalkylation of ortho-hydroxycinnamic esters via a photoredox-catalyzed cascade was developed to access a variety of 3-fluoroalkylated coumarins. This method was characterized by all-in-one synthetic design, simplified operation, mild reaction conditions, and broad substrate scope. Moreover, a sequential one-pot procedure starting from commercially available salicylaldehyde was also successfully realized to synthesize 3-fluoroalkylated coumarins.

Background and Objective: Photodynamic therapy has emerged as a promising treatment for cancer and other malignancies. Design of photosensitizers with two different action mechanisms may be an essential strategy for the improvement of the efficacy of phototherapeutic drugs. The objective of this study was to evaluate the anticancer photo- and chemocytotoxic effects of the novel half-sandwich rhodium(III) and iridium(III) photosensitizers., Materials and Methods: A series of novel half-sandwich Cp*-Rh(III) and Cp*-Ir(III) complexes containing 9-anthraldehyde thiosemicarbazones, (Cp*)M(L)Cl (M = Rh or Ir, L = 9-anthraldehyde thiosemicarbazones), were compared for cell uptake and photo- and chemocytotoxic effects against human prostate carcinoma (PC3) and human ovarian carcinoma (SKOV3) cell lines., Results: Cp*-Ir(III) complexes, (Cp*)Ir(L)Cl, showed remarkable phototoxic behavior against human ovarian adenocarcinoma SKOV3 cells (IC 50  = 2.7 and 2.3 μM, respectively, λ irr > 400 nm), as well as the 7.4 and 5.3-fold lower toxicity in the dark, implying possibility of dual action as chemo- and phototherapeutic agents., Conclusion: The complexes, which present a synergistic effect with good properties of both the Cp*-Rh(III) and Cp*-Ir(III) chemotherapeutic effect and the anthracene photodynamic therapy efficiency, show great potential as a new generation of light activated dual-action anticancer agents for photodynamic therapy., (Copyright © 2019. Published by Elsevier B.V.)

A one-pot squaramide-catalyzed enantioselective ring-reorganization domino sequence (Michael addition/intramolecular ring-opening/lactamization) of 3-hydroxyoxindole and methyleneindolinone, which can be readily derived from 3-oxindole, has been established in this work. As a result, novel polycyclic quinolinone-spirooxindoles bearing three contiguous chiral centers were efficiently and step-economically assembled under mild conditions in high yields (up to 97%) with excellent enantioselectivities (up to >99% ee) and moderate to good diastereoselectivities (up to >95:5 dr).

One-pot ring-opening/ring-closure process of combining methyleneindolinone with 3-aminooxindole has been developed in this work. Novel polycyclic spirooxindoles were efficiently assembled under mild conditions in high yields (up to 95 %) with moderate to good diastereoselectivities (up to >95:5 d.r.) through simple filtration., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A visible-light-induced difluoroalkylation of N,N'-cyclicazomethine imine was successfully realized through a novel photoredox radical-radical cross-coupling reaction. This developed protocol exhibits high functional group tolerance and affords a variety of difluorinated 3-pyrazolidinone scaffolds. Extensive mechanistic investigations have been undertaken, well revealing the involvement of a reductive radical-radical coupling pathway.

A new strategy for the synthesis of functionalized tetrahydrofuran derivatives was developed via a phosphine-catalysed [3 + 2] cyclization reaction of aromatic aldehydes with 4-phenylbut-3-yn-2-one. This is the first example of intermolecular cyclization of ynones with benzaldehydes, which essentially benefited from the intramolecular hydrogen bonding. This new protocol features a broad substrate scope, mild reaction conditions, operational simplicity and easy scale-up.

A palladium-catalyzed ring-opening oxo-formal [3 + 2]-cycloaddition reaction of novel donor-acceptor spirovinylcyclopropyl oxindole with 3-oxindole is described. The developed protocol provides facile access to oxo-bispirooxindole derivatives in good yields (up to 82% yield) with excellent diastereoselectivities (up to 20:1 dr).

A novel palladium-catalysed ring-opening [3 + 2]-annulation of spirovinylcyclopropyl oxindole with α,β-unsaturated nitroalkenes is reported. A series of spirooxindole derivatives were synthesized in high yields and good to excellent diastereoselectivities. This developed protocol offers a new and efficient pathway for the assembly of spirooxindoles.

An l-pyroglutamic acid-derived bifunctional organocatalyst was designed and applied in an organocatalytic asymmetric direct aldol reaction between isatins and cyclohexanone, in which an erosion of enantiomeric excess of aldol adduct was unexpectedly observed. Through closely monitoring the reaction and performing extensive control experiments, it was determined that the erosion of ee was attributed to a rare stereospecific retro-aldol process. Moreover, effective manipulation of the retro-aldol process by tuning the use of starting materials was ultimately accomplished, leading to evidently upgraded enantioselectivity and functional group tolerance. This study demonstrates the impact of the hidden reaction pathway on the enantioselectivity in asymmetric transformation.

A facile and enantioselective access to a functionalized octahydroacridine scaffold was developed via an organocatalytic domino sequence between cyclohexenone and 2- N-substituted benzaldehyde. High levels of yields (up to 99%) and enantioselectivities (up to 99:1 er) were readily achieved in this developed organocatalytic transformation, which holds promising applications in the construction of complex multicyclic systems for further pharmacological studies.

An efficient and diastereoselective decarboxylative oxa-1,3-dipolar cycloaddition between 3-oxindoles and diverse amino acids is developed to access novel oxazolidine-dispirooxindole skeletons bearing vicinal quaternary carbon centers. This protocol features operational simplicity, a broad substrate scope, and good to excellent chemical yields and diastereoselectivities. In particular, minimal solvent (1 mL/10 mmol) and chromatography-free purification render this synthetic process more efficient and environmentally benign in the context of green chemistry.

A facile and diversified synthesis of functionalized CF 2 -containing benzoxepine derivatives via photoredox catalysis was achieved in this work. This novel protocol features broad substrate scope, mild reaction conditions, operational simplicity, easy scale-up, and versatile derivatization, which would facilitate its practical and broad applications in the construction of valuable and synthetically challenging heterocycles.

A metal-free, mild and efficient protocol for the construction of aroylated N-heterocycles via radical cascade aroylation of phenyl or vinyl isocyanides with aromatic aldehydes has been developed. Both phenanthridine and isoquinoline derivatives are delivered quickly in moderate to good yields with high regioselectivity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

With the aid of in situ protection by N-(2-formylphenyl)-4-methyl-benzenesulfonamide, enantioselective allylic alkylation of Morita-Baylis-Hillman carbonates with diethyl 2-aminomalonate was successfully realized. The corresponding adducts can be obtained in up to 99% yield with up to 98% ee as well as excellent regioselectivity. Besides, the adducts with opposite configurations were readily prepared by utilizing easily available and inexpensive quinine or quinidine as organocatalyst. Facile deprotection of the resulting adduct provides straightforward access to enantiopure α-methylene-γ-lactam.