Photosensitized 1,2-Difunctionalization of Alkenes to Access ß-Amino Sulfonamides.

A metal-free photosensitized 1,2-imino-sulfamoylation of olefins by employing a tailor-made sulfamoyl carbamate as the difunctionalization reagent has been established. This protocol exhibits versatility across a broad substrate scope, including aryl and aliphatic alkenes, leading to the synthesis of diverse ß-imino sulfonamides in moderate to good yields. This method is characterized by its metal-free reaction system, mild reaction conditions, excellent regioselectivity, and high atom economy, serving as a promising platform for the preparation of ß-amino sulfonamide-containing molecules, particularly in the context of drug discovery.

Photoredox-Catalyzed Selective α-Scission of PR3-OH Radicals to Access Hydroalkylation of Alkenes.

Photoinduced generation of phosphoranyl radicals offers a versatile strategy to access a variety of synthetically valuable radicals. A long-standing challenge remains in the regulation of phosphoranyl radical to undergo α-scission pathway, although the ß-scission mode has been intensively studied. We herein developed an unprecedented protocol for selective α-scission of the P(OH)R3 radical intermediate under photocatalytic conditions. This efficient P-C bond cleavage via α-scission of the P(OH)R3 radicals has been successfully utilized in the alkylation/fluoroalkylation of alkenes.

Photocatalysed C-H amidation of indoles enabled by tert-butyl alkyl((perfluoropyridin-4-yl)oxy)carbamate.

Development of a new catalytic and straightforward strategy to construct C-N bonds is playing a pivotal role in synthetic chemistry. Here, we report a photocatalysed protocol to access direct C-H amidation of indoles, enabled by a rationally designed tert-butyl alkyl((perfluoropyridin-4-yl)oxy)carbamate. A series of biologically important aminoindoles were prepared under mild conditions with excellent regioselectivity and broad substrate scope.

N-Chlorosulfonyl carbamate-enabled, photoinduced amidation of quinoxalin-2(1H)-ones.

Reported herein is the design and development of a new photo-induced amidation protocol with the readily available N-chlorosulfonyl carbamate as an effective amidyl-radical precursor, which could be readily prepared from commercial low-cost chlorosulfonyl isocyanate (CSI) and alcohol feedstocks. The synthetic potency of this developed protocol was well demonstrated by direct amidation of various quinoxalin-2(1H)-ones. The protocol could be further streamlined by implementing a one-pot/two-step/three-component process of CSI, alcohol, and quinoxalin-2(1H)-one, with significantly improved reaction efficiency. This methodology offers an intriguing opportunity for rapid expansion of nitrogen-containing molecular complexity, thus inspiring comprehensive exploration of a new reaction mode of CSI reagent.

The role of KLF transcription factor in the regulation of cancer progression.

Kruppel-like factors (KLFs) are a family of zinc finger transcription factors that have been found to play an essential role in the development of various human tissues, including epithelial, teeth, and nerves. In addition to regulating normal physiological processes, KLFs have been implicated in promoting the onset of several cancers, such as gastric cancer, lung cancer, breast cancer, liver cancer, and colon cancer. To inhibit cancer progression, various existing medicines have been used to modulate the expression of KLFs, and anti-microRNA treatments have also emerged as a potential strategy for many cancers. Investigating the possibility of targeting KLFs in cancer therapy is urgently needed, as the roles of KLFs in cancer have not received enough attention in recent years. This review summarizes the factors that regulate KLF expression and function at both the transcriptional and posttranscriptional levels, which could aid in understanding the mechanisms of KLFs in cancer progression. We hope that this review will contribute to the development of more effective anti-cancer medicines targeting KLFs in the future.

Photosensitized Vicinal Sulfonylamination of Alkenes with Oxime Ester and DABCO·(SO2)2.

A metal-free photosensitized three-component reaction of oxime esters, alkenes, and DABCO·(SO2)2 was developed. This protocol could accommodate a wide substrate scope, including activated and unactivated alkenes and aryl and aliphatic carboxylic acid oxime esters, delivering a broad range of ß-amino sulfones in moderate to high yields. The insertion of SO2 as a linker moiety allows the manipulation of the functionality in the reaction process, expanding the utility of oxime esters as bifunctional reagents.

Integrin-mediated cancer progression as a specific target in clinical therapy.

Integrins, a group of heterodimer receptors for cell-matrix and cell-cell adhesion, mediate various intracellular activities, including cell migration, polarity, survival, growth, and death. Multiple types of integrins are differentially expressed in various cancers during different stages of progression, which are involved in the regulation of cancer cell proliferation, invasion, migration, and angiogenesis. The crucial roles of integrins in tumor progression provide valuable clues for cancer diagnosis and targeted therapy. Numerous integrin inhibitors have been investigated in clinical trials to explore effective regimens and minimize side effects. Given the complexity of the integrin-mediated tumor-promoting effect, challenges and difficulties remain in the research and development of integrin inhibitors, which seriously restrict the efficacy and application of integrin-targeted therapy. Novel targeted therapy of integrins, however, is beneficial for patients as a potential avenue forward, which needs better pharmacological effect, valid experimental models, and in-depth understanding of integrins. This review provides the insight needed to elucidate the mechanisms underlying cancer progression and novel protocols for the clinical treatment of cancer.

Photoredox-Catalyzed Deoxygenation of Hexafluoroacetone Hydrate Enables Hydroxypolyfluoroalkylation of Alkenes.

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.

Regioselective Access to Vicinal Diamines by Metal-Free Photosensitized Amidylimination of Alkenes with Oxime Esters.

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.

[3 + 2] vs. [4 + 1] Annulation: revisiting mechanism studies on the phosphine-catalysed domino sequence of alkynoates and activated methylenes.

The mechanism of the phosphine-catalysed domino sequence of alkynoates and activated methylenes has been computationally studied. The computational results revealed that the [3 + 2] annulation sequence could be ruled out, due to a difficult Knoevenagel condensation of aromatic aldehydes and active methylenes. The reaction proceeds through a [4 + 1] annulation pathway, which involves a phosphine-catalysed MBH-type reaction followed by a [1,5]-proton shift and dehydration to afford vinyl phosphonium intermediates as four-carbon synthons in the annulation reaction. Then 1,3-dicarbonyls act as nucleophiles to attack vinyl phosphonium intermediates, subsequently leading to a stepwise [1,3]-proton shift and an intramolecular nucleophilic attack to close the five-member ring.

Programmable iodization/deuterolysis sequences of phosphonium ylides to access deuterated benzyl iodides and aromatic aldehydes.

Herein, a tunable iodization/deuterolysis protocol for phosphonium ylides by employing D2O as the deuterium source was designed. Notably, this process could be manipulated by tuning the base, thus leading to two valuable deuterated building blocks - benzyl iodides and aromatic aldehydes with broad substrate scope, good functional group compatibility and excellent deuteration degree. Concise syntheses of a series of deuterated drug analogues have been achieved based on the developed deuteration reaction platform.

Visible-Light-Induced, Palladium-Catalyzed 1,4-Difunctionalization of 1,3-Dienes with Bromodifluoroacetamides.

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 CF2-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.

Phosphine-Mediated Morita-Baylis-Hillman-Type/Wittig Cascade: Access to E-Configured 3-Styryl- and 3-(Benzopyrrole/furan-2-yl) Quinolinones.

A phosphine-mediated, well-designed Morita-Baylis-Hillman-type/Wittig cascade for the rapid assembly of a quinolinone framework from benzaldehyde derivatives is developed for the first time. By rationally combining I2/NIS-mediated cyclization, biologically relevant 3-(benzopyrrole/furan-2-yl) quinolinones were facilely synthesized in a one-pot process by starting from 3-styryl-quinolinones bearing an o-hydroxy/amino group, significantly expanding the chemical space of this privileged skeleton. Further utility of this protocol is illustrated by successfully performing this transformation in a catalytic manner through in situ reduction of phosphine oxide by phenylsilane.

Visible-Light-Promoted Hydroxydifluoroalkylation of Alkenes Enabled by Electron Donor-Acceptor Complex.

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.

A phosphine-catalysed one-pot domino sequence to access cyclopentene-fused coumarins.

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.

Phosphonium Ylide-Mediated Programmable Fluorination to Access Mono- and Difluoromethylarenes.

Compounds bearing fluorinated moieties are pervasive in a wide range of pharmaceuticals and agrochemicals. The installation of fluorinated units is a persistently vital task in synthetic chemistry, where facile and manipulable assays are highly demanding. Herein, we establish a general and programmable fluorination strategy for the modular assembly of mono- and difluoromethylarenes through the controllable deprotonation and fluorination of phosphonium ylides. Moreover, the rational combination of the reaction sequence allows the rapid construction of diversified fluorine-containing arenes.

A phosphine-mediated domino sequence of salicylaldehyde with but-3-yn-2-one: rapid access to chromanone.

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.

High-quality genome assembly and transcriptome of Ancherythroculter nigrocauda, an endemic Chinese cyprinid species.

Ancherythroculter nigrocauda is a cyprinid fish endemic of the upper reaches of the Yangtze River in China, where it is an important aquaculture and commercial species. It is also a threatened species as a result of overfishing, dam construction and water pollution. In this study, a chromosome-level genome assembly of A. nigrocauda is reported and built using PacBio sequencing and the Hi-C technology. The 1.04-Gb sequenced genome of A. nigrocauda contained 2,403 contigs, with an N50 length of 3.12 Mb. Then, 1,297 contigs, which represented 54.0% of all contigs and 97.2% of the whole content of the genome nucleotide base, were assembled into 24 chromosomes. Combined with transcriptome data from 10 tissues, 27,042 (78.5%) genes were functionally annotated out of 34,414 predicted protein-coding genes. Interestingly, high expression of many positively selected genes and expanded gene families in the brain suggested that these genes might play important roles in brain development in A. nigrocauda. Finally, we found tissue-specific expression of 10,732 genes. Functional analyses showed that they were mainly composed of genes related to (a) environmental information processing, (b) the circulatory system, and (c) development, suggesting they might be important for adaptation to different environments and for development of A. nigrocauda. The high-quality genome obtained in this study not only provides a valuable genomic resource for future studies of A. nigrocauda populations and conservation, but is also an important resource for further functional genomics studies of fishes.

Phosphine-Mediated MBH-Type/Umpolung Addition Domino Sequence: Divergent Construction of Coumarins.

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.

Organocatalytic, Enantioselective, Polarity-Matched Ring-Reorganization Domino Sequence Based on the 3-Oxindole Scaffold.

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).