Metal-free directed sp2-C-H borylation.

Organoboron reagents are important synthetic intermediates that have a key role in the construction of natural products, pharmaceuticals and organic materials1. The discovery of simpler, milder and more efficient approaches to organoborons can open additional routes to diverse substances2-5. Here we show a general method for the directed C-H borylation of arenes and heteroarenes without the use of metal catalysts. C7- and C4-borylated indoles are produced by a mild approach that is compatible with a broad range of functional groups. The mechanism, which is established by density functional theory calculations, involves BBr3 acting as both a reagent and a catalyst. The potential utility of this strategy is highlighted by the downstream transformation of the formed boron species into natural products and drug scaffolds.

Genomics insights into flowering and floral pattern formation: regional duplication and seasonal pattern of gene expression in Camellia.

BACKGROUND: The formation and domestication of ornamental traits are influenced by various aspects, such as the recognition of esthetic values and cultural traditions. Camellia japonica is widely appreciated and domesticated around the world mainly due to its rich variations in ornamental traits. Ornamental camellias have a diverse range of resources, including different bud variations from Camellia spp. as well as inter- and intra- specific hybridization. Despite research on the formation of ornamental traits, a basic understanding of their genetics and genomics is still lacking. RESULTS: Here, we report the chromosomal-level reference genome of C. japonica through combining multiple DNA-sequencing technologies and obtain a high-density genetic linkage map of 4255 markers by sequencing 98 interspecific F1 hybrids between C. japonica and C. chekiangoleosa. We identify two whole-genome duplication events in C. japonica: one is a shared ancient γ event, and the other is revealed to be specific to genus Camellia. Based on the micro-collinearity analysis, we find large-scale segmental duplication of chromosome 8, resulting to two copies of the AGAMOUS loci, which may play a key role in the domestication of floral shapes. To explore the regulatory mechanisms of seasonal flowering, we have analyzed year-round gene expression patterns of C. japonica and C. azalea-a sister plant of continuous flowering that has been widely used for cross breeding. Through comparative analyses of gene co-expression networks and annual gene expression patterns, we show that annual expression rhythms of some important regulators of seasonal growth and development, including GIGANTEA and CONSTANS of the photoperiod pathway, have been disrupted in C. azalea. Furthermore, we reveal that the distinctive expression patterns of FLOWERING LOCUS T can be correlated with the seasonal activities of flowering and flushing. We demonstrate that the regulatory module involved in GIGANTEA, CONSTANS, and FLOWERING LOCUS T is central to achieve seasonality. CONCLUSIONS: Through the genomic and comparative genomics characterizations of ornamental Camellia spp., we propose that duplication of chromosomal segments as well as the establishment of gene expression patterns has played a key role in the formation of ornamental traits (e.g., flower shape, flowering time). This work provides a valuable genomic platform for understanding the molecular basis of ornamental traits.

P(III)-Directed Asymmetric C-H Arylation toward Planar Chiral Ferrocenes by Palladium Catalysis.

Planar chiral ferrocenyl phosphines have been employed as highly valuable ligands in metal-catalyzed asymmetric reactions. However, their preparation remains a formidable challenge due to the requirement for intricate, multistep synthetic sequences. In addressing this issue, we have developed a groundbreaking enantioselective C-H activation strategy facilitated by P(III) directing groups, enabling the efficient construction of planar chiral ferrocenyl phosphines in a single step. Our innovative approach entails the combination of a palladium catalyst, a parent ferrocenyl phosphine, and a chiral phosphoramidite ligand, leading to exceptional reactivity and enantioselectivity. Remarkably, these novel ligands exhibit remarkable efficacy in silver-catalyzed asymmetric 1,3-dipolar cycloadditions. We carried out a combination of experimental and computational studies to obtain a more comprehensive understanding of the reaction pathway and the factors contributing to enantioselectivity.

Asymmetric 2,3-Addition of Sulfinylamines with Arylboronic Acids Enabled by Nickel Catalysis.

Sulfinamides have been widely used in organic synthesis, with research on their preparation spanning more than a century. Despite advancements in catalytic methodologies, creating sulfur stereocenters within these molecules remains a significant challenge. In this study, we present an effective and versatile method for synthesizing a diverse range of S-chirogenic sulfinamides through catalytic asymmetric aryl addition to sulfinylamines. By utilizing a nickel complex as a catalyst, this process exhibits impressive enantioselectivity and can incorporate various arylboronic acids at the sulfur position. The resulting synthetic sulfinamides are stable and highly adaptable, allowing for their conversion to a variety of sulfur-containing compounds. Our study also incorporates detailed experimental and computational studies to elucidate the reaction mechanism and factors influencing enantioselectivity.

Palladium-Catalyzed Divergent Enantioselective Functionalization of Cyclobutenes.

Aliphatic strained rings have been increasingly applied in medicinal chemistry due to their beneficial physicochemical and pharmacokinetic properties. However, the divergent synthesis of enantioenriched cyclobutane derivatives with various structural patterns continues to be a significant challenge. Here, we disclose a palladium-catalyzed enantioselective desymmetrization of cyclobutenes, resulting in a series of hydroarylation and 1,2- and 1,3-diarylation products via the interceptions of a common Heck intermediate. Mechanistic investigations provide valuable insights into understanding the catalytic mode of the palladium catalysts and the observed variations in the deuterium-responsive behavior during reactions. Furthermore, the synthetic utility is demonstrated in the syntheses of deuterated drug candidate belaperidone skeletons and pseudosymmetrical truxinic acid-type derivatives.

Challenging Task of Ni-Catalyzed Highly Regio-/Enantioselective Semihydrogenation of Racemic Tetrasubstituted Allenes via a Kinetic Resolution Process.

The first earth-abundant transition metal Ni-catalyzed highly regio- and enantioselective semihydrogenation of racemic tetrasubstituted allenes via a kinetic resolution process as a challenging task was well established. This protocol furnishes expedient access to a diversity of structurally important enantioenriched tetrasubstituted allenes and chiral allylic molecules with high regio-, enantio-, and Z/E-selectivity. Remarkably, this semihydrogenation proceeded with one carbon-carbon double bond of allenes, which was regioselective complementary to the Rh-catalyzed asymmetric version. Deuterium labeling experiments and density functional theory (DFT) calculations were carried out to reveal the reasonable reaction mechanism and explain the regio-/stereoselectivity.

Ligand-Controlled, Nickel-Catalyzed Stereodivergent Construction of 1,3-Nonadjacent Stereocenters.

In contrast to the asymmetric synthesis of molecules with a single stereocenter or 1,2-adjacent stereocenters, the simultaneous construction of acyclic 1,3-nonadjacent stereocenters via a single catalyst in an enantioselective and diastereoselective manner remains a formidable challenge. Here, we demonstrate the enantioselective and diastereodivergent construction of 1,3-nonadjacent stereocenters through Ni-catalyzed reductive cyclization/cross-coupling of alkene-tethered aryl bromides and α-bromoamides, which represents the major remaining stereochemical challenge of cyclization/difunctionalization of alkenes. Using Ming-Phos as ligand, a diverse set of oxindoles containing 1,3-nonadjacent stereocenters were obtained with high levels of enantio- and diastereoselectivity. Mechanistic experiments and density functional theory calculations indicate that magnesium salt plays a key role in controlling the diastereoselectivity. Furthermore, another set of complementary stereoisomeric products were constructed from the same set of starting materials using Ph-Phox as ligand.

Integrative Analysis of Small RNA and Gene Expression Uncovers a Novel Long-Noncoding MicroRNA Targeting a UDP-Transferase in Camellia chekiangoleosa.

Biosynthesis of specific secondary metabolites in plants involves fine regulation of gene expression. Camellia chekiangoleosa has important economic value: the seeds contain high-quality unsaturated fatty acids and the pericarp is rich in tea saponins. As an important posttranscriptional regulator, the role of microRNAs (miRNAs) in controlling secondary metabolism in C. chekiangoleosa is not fully studied. Here, we investigated the role of miRNAs and their targets in the secondary metabolic regulatory network by comprehensively analyzing small RNAs, transcriptomes, and degradomes from different tissues. We identified 168 known miRNAs and 74 novel miRNAs in the C. chekiangoleosa genome and revealed 15 tandem clusters containing 35 miRNAs. By establishing a gene regulatory network containing miRNAs, target genes, and transcription factors, we unravelled the multiplicity of miRNA tissue-specific regulation of gene expression, which may be tightly linked to the synthesis of secondary metabolites. Furthermore, we characterized a novel long-noncoding miRNA gene (cch-miR3633) that targeted a UDP-transferase gene (CchUGT94E5). We showed that, ectopic expression of CchUGT94E5 caused outgrowth of shoot branching and changes in cytokinin contents in Arabidopsis, indicating a potential role of regulating secondary metabolism. This work provides valuable information for the study of miRNA regulation of secondary metabolism.

Modeling and oblique transmission characteristics of an underwater wireless optical communication channel based on ocean depth layering.

Underwater wireless optical communication is widely considered in the field of underwater communication due to its high bandwidth and low latency. In a real transmission link, the temperature and salinity of seawater, chlorophyll concentration, and bubble density vary with ocean depth. Therefore, the depth of the optical transmitter in seawater and the tilt angle of the beam will exhibit different beam transmission characteristics. In this paper, an underwater oblique-range layered channel model considering the combined effects of dynamic turbulence, absorption, and scattering is developed based on real data of seawater at different depths measured by the Global Ocean Observing Buoy Argo and the Woods Hole Oceanographic Institution BCO-DMO. The effects of transmission distance, transmitter tilt angle, and transmitter depth on the oblique-range transmission characteristics of the beam in seawater are discussed. The simulation results show that, at the same transmission distance, the beam centroid displacement increases with an increase in transmitter depth only when the transmitter is located above the interior of the thermocline. When the transmitter is located below the interior of the thermocline, the influence of the transmitter tilt angle on the beam centroid displacement decreases. This indicates that at different depths within the interior of the thermocline, the optical beam transmission characteristics exhibit significant variations.

Converting flooded rice to dry farming can alleviate MeHg accumulation in grains.

The study explored the impact of water management on rice cultivation in mercury-contaminated paddy soil. The objective was to analyze the characteristics of mercury translocation by converting flooded soils to dry farming (non-flooded) to alleviate mercury accumulation in rice grains. The experiment was conducted over three consecutive rice-growing seasons, employing two distinct water management models: a continuously flooded rice cultivation mode and a flooded rice planting mode in the first season, followed by a non-flooded rice farming mode in the second and third seasons. The results showed that the change from flooded to non-flooded rice cultivation patterns presented extremely excellent environmental potential for inhibiting the uptake of both methylmercury and total mercury in rice. When transitioning from flooded cultivation to dry farming, the concentration of methylmercury and total mercury in the grains of non-flooded rice decreased by 87.15 % and 9.57 %, respectively, compared to that in the grains of flooded rice. In the third season, the methylmercury and total mercury in the grains of non-flooded rice decreased further by 95.03 % and 69.45 %, respectively. This study verified that the conversion of rice cultivation from flooded to non-flooded is an efficient strategy for suppressing the accumulation of methylmercury in rice grains, and it might offer a promising solution for managing soil mercury risks and ensuring the safety of rice for human consumption.

Algae decomposition released dissolved organic matter subfractions on dark abiotic mercury methylation.

To understand the mechanism of dark abiotic mercury (Hg) methylation by algae-derived dissolved organic matter (DOM) and effectively manage the environmental risks of mercury methylation in aquaculture areas, we investigated the influence of subfractions of DOM released from algae (Ulothrix sp.) decomposition on mercury methylation. The results showed that the hydrophobic basic component (HOB) in DOM exhibited the most substantial promotion effect on Hg methylation. The methylmercury (MeHg) production in the HOB treatment increased significantly, while the production rate of MeHg (%MeHg represented the concentration ratio of MeHg to THg) in the six subfractions treated solutions decreased significantly with the increase of Hg concentration. The change of the %MeHg was more evident at low Hg concentration, indicating the limited number of binding sites and methyl donors on DOM. As a consequence, Hg(Ⅱ) in the solution could not be converted into MeHg in equal proportion. Furthermore, the production of MeHg in solution was significantly reduced by the decomposed algae DOM, and its concentration was in the range of 0.017-0.085 ng·L-1 (significantly lower than undecomposed algal). The difference between the decomposed and the non-decomposed algae DOM reached a significant level (P < 0.05). When the DOM decayed for 20 and 30 days, the Hg methylation ability of DOM was weakened most obviously. During the decomposition process, considerable variations were observed among the subfractions, with HOB consistently playing a dominant role in Hg methylation. At the same time, the hydrophilic acid component exhibited a significant inhibitory effect on Hg methylation. Generally, the main components (e.g. HOB and HIA (hydrophilic acid component)) of DOM affecting mercury methylation were found in our study, which provided a better understanding of algae-derived DOM subfractions on the Hg methylation, in an attempt to prevent and control water pollution in aquaculture areas.

Genome-Wide Analysis of MADS-Box Gene Family Reveals CjSTK as a Key Regulator of Seed Abortion in Camellia japonica.

The plant MADS-box transcription factor family is a major regulator of plant flower development and reproduction, and the AGAMOUS-LIKE11/SEEDSTICK (AGL11/STK) subfamily plays conserved functions in the seed development of flowering plants. Camellia japonica is a world-famous ornamental flower, and its seed kernels are rich in highly valuable fatty acids. Seed abortion has been found to be common in C. japonica, but little is known about how it is regulated during seed development. In this study, we performed a genome-wide analysis of the MADS-box gene the in C. japonica genome and identified 126 MADS-box genes. Through gene expression profiling in various tissue types, we revealed the C/D-class MADS-box genes were preferentially expressed in seed-related tissues. We identified the AGL11/STK-like gene, CjSTK, and showed that it contained a typical STK motif and exclusively expressed during seed development. We found a significant increase in the CjSTK expression level in aborted seeds compared with normally developing seeds. Furthermore, overexpression of CjSTK in Arabidopsis thaliana caused shorter pods and smaller seeds. Taken together, we concluded that the fine regulation of the CjSTK expression at different stages of seed development is critical for ovule formation and seed abortion in C. japonica. The present study provides evidence revealing the regulation of seed development in Camellia.

Molecular Mechanisms of Seasonal Gene Expression in Trees.

In trees, the annual cycling of active and dormant states in buds is closely regulated by environmental factors, which are of primary significance to their productivity and survival. It has been found that the parallel or convergent evolution of molecular pathways that respond to day length or temperature can lead to the establishment of conserved periodic gene expression patterns. In recent years, it has been shown in many woody plants that change in annual rhythmic patterns of gene expression may underpin the adaptive evolution in forest trees. In this review, we summarize the progress on the molecular mechanisms of seasonal regulation on the processes of shoot growth, bud dormancy, and bud break in response to day length and temperature factors. We focus on seasonal expression patterns of genes involved in dormancy and their associated epigenetic modifications; the seasonal changes in the extent of modifications, such as DNA methylation, histone acetylation, and histone methylation, at dormancy-associated loci have been revealed for their actions on gene regulation. In addition, we provide an outlook on the direction of research on the annual cycle of tree growth under climate change.

Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity.

BACKGROUND: Src family kinases (SFKs) contribute to migraine pathogenesis, yet its role in regulating photophobia behaviour, one of the most common forms of migraine, remains unknown. Here, we addressed whether SFKs antagonism alleviates photophobia behavior and explored the underlying mechanism involving hypothalamus and trigeminal ganglion activity, as measured by the alteration of neuropeptide levels and transcriptome respectively. METHODS: A rapid-onset and injury-free mouse model of photophobia was developed following intranasal injection of the TRPA1 activator, umbellulone. The role of SFKs antagonism on light aversion was assessed by the total time the mouse stays in the light and transition times between the dark and light compartments. To gain insight to the preventive mechanism of SFKs antagonism, hypothalamic neuropeptides levels were assessed using enzyme linked immunofluorescent assay and trigeminal ganglion activity were assessed using RNA-sequencing and qPCR analysis. RESULTS: SFKs antagonism by a clinically relevant SFKs inhibitor saracatinib reduced the total time in light and transition times in male mice, but not in females, suggesting SFKs play a crucial role in photophobia progressing and exhibit a male-only effect. SFKs antagonism had no effect on hypothalamic calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide levels of all mice investigated, suggesting the gender-different effect of saracatinib on light aversion appears to be independent of these hypothalamic neuropeptide levels. In trigeminal ganglion of male mice, photophobia is associated with profound alteration of differentially expressed genes, part of which were reversed by SFKs antagonism. Subsequent qPCR analysis showed SFKs antagonism displayed gender-different modulation of expression in some candidate genes, particularly noteworthy those encoding ion channels (trpm3, Scn8a), ATPase signaling (crebbp, Atp5α1) and kinase receptors (Zmynd8, Akt1). CONCLUSIONS: In conclusion, our data revealed that SFKs antagonism reduced photophobia processing in male mice and exhibited gender-different modulation of trigeminal ganglion activity, primarily manifesting as alterations in the transcriptome profile. These findings underscore the potential of SFKs antagonism for allieving photophobia in males, highlighting its value in the emerging field of precision medicine.

Spirobipyridine Ligand Enabled Iridium-Catalyzed Site-Selective C-H Activation via Non-Covalent Interactions.

The selective borylation of specific C-H bonds in organic synthesis remains a formidable challenge. In this study, we present a novel spirobipyridine ligand that features a binaphthyl backbone. This ligand facilitates the iridium-catalyzed selective C-H borylation of benzene derivatives. The ligand is designed with "side-arm-wall" substituents that allow vicinal di- or multi-substituted benzene derivatives to approach metal center and effectively block other reactive sites by non-covalent interactions with substrates. The effectiveness of this strategy is demonstrated by the successful selective distal C-H activation of various alkaloids and its broad compatibility with functional groups.

Nickel-Catalyzed Asymmetric Propargyl-Aryl Cross-Electrophile Coupling.

Performing asymmetric cross-coupling reactions between propargylic electrophiles and aryl nucleophiles is a well-established method to build enantioenriched benzylic alkynes. Here, a catalytic enantioselective propargyl-aryl cross-coupling between two electrophiles was achieved for the first time in a stereoconvergent manner. Propargylic chlorides were treated with aryl iodides as well as heteroaryl iodides in the presence of a chiral nickel complex, and manganese metal was used as a stoichiometric reductant, allowing for the construction of a propargyl C-aryl bond under mild conditions. An alternative dual nickel/photoredox catalytic protocol was also developed for this cross-electrophile coupling in the absence of a metal reductant. The potential utility of this conversion is demonstrated in the facile construction of stereoenriched bioactive molecule derivatives and medicinal compounds based on the diversity of acetylenic chemistry. Detailed experimental studies have revealed the key mechanistic features of this transformation.

Enantioselective Rhodium-Catalyzed C-H Arylation Enables Direct Synthesis of Atropisomeric Phosphines.

Atropisomeric phosphines hold considerable significance in asymmetric catalysis, yet their synthesis presents a formidable challenge owing to intricate multistep procedures. In this context, a groundbreaking methodology has been presented for their preparation. This innovative approach entails an atroposelective rhodium-catalyzed C-H activation employing aryl and heteroaryl halides, chelated by a P(III) center. The essence of this strategy lies in its ability to directly construct chiral phosphine ligands in a single step, thereby exhibiting exceptional efficiency in terms of atom and redox economy. Illustrative examples serve to demonstrate the immense potential of in situ-formed ligands in asymmetric catalysis. Mechanistic experiments have further provided invaluable insights into this transformation.

Ni-Catalyzed Enantioselective Reductive Cyclization/Amidation and Amination of 1,6-Enynes and 1,7-Enynes.

Transition-metal-catalyzed hydroamination of unsaturated hydrocarbons is an appealing synthetic tool for the construction of high value-added chiral amines. Despite significant progress in the asymmetric hydroamination of alkenes, allenes, and 1,3-dienes, asymmetric hydroamination of 1,6-enynes or 1,7-enynes remains rather limited due to the enormous challenges in controlling the chemoselectivity and stereoselectivity of the reaction. Herein, we report a Ni-catalyzed chemo- and enantioselective reductive cyclization/amidation and amination of 1,6-enynes and 1,7-enynes using dioxazolones or anthranils as nitrene-transfer reagents. This mild, modular, and practical protocol provides rapid access to a variety of enantioenriched 2-pyrrolidone and 2-piperidone derivatives bearing an aminomethylene group at the 4-position in good yields (up to 83%) with excellent enantioselectivities (40 examples, up to 99% ee). Mechanistic experiments and density functional theory calculations indicate that the reaction is initiated by hydronickelation of alkynes followed by migratory insertion into alkenes, rather than by a [2+2+1] oxidative addition process of nickel to alkenes and alkynes.

Stereoselective Vinylic C-H Addition via Metallaphotoredox Migration.

Geometrically defined allylic alcohols with SE, SZ, RE and RZ stereoisomers serve as valuable intermediates in synthetic chemistry, attributed to the stereoselective transformations enabled by the alkenyl and hydroxyl functionalities. When an ideal scenario presents itself with four distinct stereoisomers as potential products, the simultaneous control vicinal stereochemistry in a single step would offer a direct pathway to any desired stereoisomer. Here, we unveil a metallaphotoredox migration strategy to access stereodefined allylic alcohols through vinylic C-H activation with aldehydes. This method harnesses a chiral nickel catalyst in concert with a photocatalyst to enable a 1,4-Ni migration by using readily accessible 2-vinyl iodoarenes as starting materials. The efficacy of this methodology is highlighted by the precise construction of all stereoisomers of allylic alcohols bearing analogous substituents and the efficient synthesis of key intermediates en route to Myristinin family. Experimental and computational studies have shed light on pivotal aspects including the synergy of metal catalysis and photocatalysis, the driving forces behind the migration, and the determination of absolute configuration in the C-H addition process.

Hydrodeuteroalkylation of Unactivated Olefins Using Thianthrenium Salts.

Isotopically labeled alkanes play a crucial role in organic and pharmaceutical chemistry. While some deuterated methylating agents are readily available, the limited accessibility of other deuteroalkyl reagents has hindered the synthesis of corresponding products. In this study, we introduce a nickel-catalyzed system that facilitates the synthesis of various deuterium-labeled alkanes through the hydrodeuteroalkylation of d2-labeled alkyl TT salts with unactivated alkenes. Diverging from traditional deuterated alkyl reagents, alkyl thianthrenium (TT) salts can effectively and selectively introduce deuterium at α position of alkyl chains using D2O as the deuterium source via a single-step pH-dependent hydrogen isotope exchange (HIE). Our method allows for high deuterium incorporation, and offers precise control over the site of deuterium insertion within an alkyl chain. This technique proves to be invaluable for the synthesis of various deuterium-labeled compounds, especially those of pharmaceutical relevance.