Reductive anti-Dizincation of Arylacetylenes.

Arylacetylenes undergo anti-1,2-dizincation to afford trans-1,2-dizincioalkenes. The process employs sodium dispersion as a reducing agent and zinc chloride TMEDA complex as a reduction-resistant zinc electrophile. This reductive anti-dizincation contrasts with the conventional additive syn-dimetalation like silylzincation. The resulting dizincated alkenes undergo the cross-coupling to yield multi-substituted alkenes stereoselectively.

Sodium-Mediated Reductive C-C Bond Cleavage Assisted by Boryl Groups.

In contrast to the well-established oxidative C=C double bond cleavage to give the corresponding carbonyl compounds, little is known about reductive C=C double bond cleavage. Here we report that C-C single bond cleavage in 1,2-diaryl-1,2-diborylethanes proceeds by reduction with sodium metal to yield α-boryl benzylsodium species. In combination with our previous reductive diboration of stilbenes, the overall transformation represents reductive cleavage of the C=C double bonds of stilbene to yield α-boryl-α-sodiated toluenes. This reductive two-step C=C double bond cleavage is applicable to ring-opening or ring-expansion reactions of polycyclic aromatic hydrocarbons.

Development of sexual dimorphism of skeletal muscles through the adrenal cortex, caused by androgen-induced global gene suppression.

The zona fasciculata (zF) in the adrenal cortex contributes to multiple physiological actions through glucocorticoid synthesis. The size, proliferation, and glucocorticoid synthesis characteristics are all female biased, and sexual dimorphism is established by androgen. In this study, transcriptomes were obtained to unveil the sex differentiation mechanism. Interestingly, both the amount of mRNA and the expressions of nearly all genes were higher in females. The expression of Nr5a1, which is essential for steroidogenic cell differentiation, was also female biased. Whole-genome studies demonstrated that NR5A1 regulates nearly all gene expression directly or indirectly. This suggests that androgen-induced global gene suppression is potentially mediated by NR5A1. Using Nr5a1 heterozygous mice, whose adrenal cortex is smaller than the wild type, we demonstrated that the size of skeletal muscles is possibly regulated by glucocorticoid synthesized by zF. Taken together, considering the ubiquitous presence of glucocorticoid receptors, our findings provide a pathway for sex differentiation through glucocorticoid synthesis.

Oxidative Addition of Aryl Electrophiles into a Red-Light-Active Bismuthinidene.

The oxidative addition of aryl electrophiles is a fundamental organometallic reaction widely applied in the field of transition metal chemistry and catalysis. However, the analogous version based on main group elements still remains largely underexplored. Here, we report the ability of a well-defined organobismuth(I) complex to undergo formal oxidative addition with a wide range of aryl electrophiles. The process is facilitated by the reactivity of both the ground and excited states of N,C,N-bismuthinidenes upon absorption of low-energy red light.

Stereoselective Synthesis of Tetraarylethylenes Enabled by Reductive anti-1,2-Dimetallation of Alkynes.

Tetraarylethylenes (TAEs) have been gaining attention from various scientific disciplines for their characteristic chemical and physical properties. From the synthetic perspective, however, efficient methods for the selective synthesis of different isomers of TAEs are still underdeveloped. Here, we report the regio- and stereoselective synthesis of TAEs by means of sodium-promoted reductive anti-1,2-dimagnesiation of alkynes. Subsequent transmetallation to zinc generates trans-1,2-dizincioalkenes, which underwent the stereoselective arylation under a palladium catalysis to afford a variety of TAEs that had been difficult to prepare according to the conventional procedures. In addition, the present method accommodates not only diarylacetylenes but also alkyl aryl acetylenes and thus enables to synthesize a wide range of all-carbon tetrasubstituted alkenes.

Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway.

Leydig cells in fetal testes play crucial roles in masculinizing fetuses through androgen production. Gene knockout studies have revealed that growth factors are implicated in fetal Leydig cell (FLC) differentiation, but little is known about the mechanisms regulating this process. We investigate this issue by characterizing FLC progenitor cells using single-cell RNA sequencing. The sequence datasets suggest that thymosin ß10 (Tmsb10) is transiently upregulated in the progenitors. While studying the function of Tmsb10, we reveal that platelet-derived growth factor (PDGF) regulates ciliogenesis through the RAS/ERK and PI3K/AKT pathways, and thereby promotes desert hedgehog (DHH)-dependent FLC differentiation. Tmsb10 expressed in the progenitor cells induces their differentiation into FLCs by suppressing the RAS/ERK pathway. Through characterizing the transiently expressed Tmsb10 in the FLC progenitors, this study unveils the molecular process of FLC differentiation and shows that it is cooperatively induced by DHH and PDGF.

Syn and Anti Metal Complexes of 24π Antiaromatic Bis(Dicarbonylrhodium(I))Dithiaamethyrin.

From the reaction of sterically less hindered tetrapropyl[24]dithiaamethyrin(1.0.0.1.0.0) 5, with [Rh(CO)2 Cl]2 , a unique anti form of the bis(dicarbonylrhodium(I)) complex (6-anti), where two rhodium ions are on the opposite faces of the macrocyclic ligand, was isolated for the first time in 12% yield along with the corresponding syn isomer (6-syn, 61% yield). These structures were characterized in detail by single-crystal X-ray structure analysis. Compound 6-syn exhibited a bowl-shaped structure with the two rhodium atoms separated by a distance of ∼4.5 Å. In contrast, 6-anti contained a wave-shaped macrocycle with a distance of ∼5.3 Šbetween the two rhodium atoms. Furthermore, the 1 H nuclear magnetic resonance spectra and density functional theory calculation results revealed that 6-anti had a stronger paratropic ring current and a more planar structure than 6-syn. The isolation of both 6-anti and 6-syn enabled detailed discussion of the structure-property relationship.

Effects of exposure to oxytetracycline on the liver proteome of red seabream (Pagrus major) in a real administration scenario.

Oxytetracycline (OTC) is a widely used antibiotic in aquaculture. In this study, red seabream (Pagrus major), the most popular aquaculture species in Japan, were treated with OTC mimicking a real administration scenario in aquaculture. The treatment groups were as follows: no OTC, 40 mg/kg body wt/day (equivalent to the dose used in actual aquaculture), or 178 mg/kg body wt/day. The first exposure was conducted for a week (1st OTC exposure period), followed by a 4-week interval, and the second exposure was for one week (2nd OTC exposure period). We investigated the effects of OTC on the liver proteome with the isobaric tags for relative and absolute quantitation (iTRAQ) technology accompanied by liquid chromatography and mass spectrometry. The pathway and disease enrichment analyses of differentially abundant proteins in OTC-exposed groups compared to their respective controls showed that the abundance of proteins related to the immune and nervous systems was altered after the 1st and 2nd OTC exposures, respectively. Quantitative real-time PCR of the transcripts of immune-related genes corroborated with the results of proteome analysis. OTC exposure also modulated the expression of metabolism-related proteins after the 1st and 2nd OTC exposures. Furthermore, after four weeks of the 2nd exposure, weight loss and changes in the expression of proteins related to metabolism were observed, suggesting that OTC exposure disrupts the metabolic system and causes growth inhibition. Based on these results, we suggest that the use of OTC in aquaculture poses a health risk in fish species. Thus, we need to pay more attention to the contamination with OTC in aquaculture.

Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle.

Skeletal muscles display sexually dimorphic features. Biochemically, glycolysis and fatty acid ß-oxidation occur preferentially in the muscles of males and females, respectively. However, the mechanisms of the selective utilization of these fuels remains elusive. Here, we obtain transcriptomes from quadriceps type IIB fibers of untreated, gonadectomized, and sex steroid-treated mice of both sexes. Analyses of the transcriptomes unveil two genes, Pfkfb3 (phosphofructokinase-2) and Pdk4 (pyruvate dehydrogenase kinase 4), that may function as switches between the two sexually dimorphic metabolic pathways. Interestingly, Pfkfb3 and Pdk4 show male-enriched and estradiol-enhanced expression, respectively. Moreover, the contribution of these genes to sexually dimorphic metabolism is demonstrated by knockdown studies with cultured type IIB muscle fibers. Considering that skeletal muscles as a whole are the largest energy-consuming organs, our results provide insights into energy metabolism in the two sexes, during the estrus cycle in women, and under pathological conditions involving skeletal muscles.

Reductive Cleavage of Propargylic Ethers with Alkali Metal: Application to the Synthesis of Allenylboronates.

Treatment of propargylic ethers with sodium dispersion in the presence of lithium iodide results in the generation of the corresponding carbanion species via cleavage of the propargylic C-O bond. The anionic species react with trimethoxyborane to yield the allenylboronates including highly substituted ones that are difficult to synthesize.

Sodium-Promoted Borylation of Polycyclic Aromatic Hydrocarbons.

Sodium dispersion promotes the reductive borylation of polycyclic aromatic hydrocarbons (PAHs) with MeOBpin. Anthracenes and phenanthrenes are converted to the corresponding dearomatized diborylated products. The reductive diborylation of naphthalene-based small π-systems yields similar yet unstable products that are oxidized into formal C-H borylation products with unique regioselectivity. Pyrene is converted to 1-borylpyrene without the addition of an oxidant. The latter two reactions represent a new route to useful borylated PAHs that rivals C-X borylation and catalytic C-H borylation.

Gene expression and functional abnormalities in XX/Sry Leydig cells.

The SRY gene induces testis development even in XX individuals. However, XX/Sry testes fail to produce mature sperm, due to the absence of Y chromosome carrying genes essential for spermatogenesis. XX/Sry Sertoli cells show abnormalities in the production of lactate and cholesterol required for germ cell development. Leydig cells are essential for male functions through testosterone production. However, whether XX/Sry adult Leydig cells (XX/Sry ALCs) function normally remains unclear. In this study, the transcriptomes from XY and XX/Sry ALCs demonstrated that immediate early and cholesterogenic gene expressions differed between these cells. Interestingly, cholesterogenic genes were upregulated in XX/Sry ALCs, although downregulated in XX/Sry Sertoli cells. Among the steroidogenic enzymes, CYP17A1 mediates steroid 17α-hydroxylation and 17,20-lyase reaction, necessary for testosterone production. In XX/Sry ALCs, the latter reaction was selectively decreased. The defects in XX/Sry ALCs, together with those in the germ and Sertoli cells, might explain the infertility of XX/Sry testes.

Reductive Difunctionalization of Aryl Alkenes with Sodium Metal and Reduction-Resistant Alkoxy-Substituted Electrophiles.

A general method for alkali-metal-promoted reductive difunctionalization of alkenes has been developed by means of reduction-resistant alkoxy-substituted electrophiles. A series of 1,2-diboration and 1,2-dicarbofunctionalization products can be synthesized by employing trimethoxyborane and strained cyclic ethers such as oxirane and oxetane. In addition, unsymmetrical carbo- or thioborations have been accomplished via sequential treatment with trimethoxyborane and carbon or sulfur electrophiles.

Diborative Reduction of Alkynes to 1,2-Diboryl-1,2-Dimetalloalkanes: Its Application for the Synthesis of Diverse 1,2-Bis(boronate)s.

Reduction of alkynes with alkali metals in the presence of B2pin2 results in diboration of alkynes. Distinct from conventional dissolving metal hydrogenations, two carbon-boron bonds and also two carbon-alkali metal bonds can be constructed in one operation to form 1,2-diboryl-1,2-dimetalloalkanes. The 1,2-diboryl-1,2-dimetalloalkanes generated are readily convertible to a wide range of vicinal bis(boronate)s. In particular, oxidation of the 1,2-dianionic species provides ( E)-1,2-diborylalkenes, unique anti-selective diboration of alkynes being thus executed.

Three populations of adult Leydig cells in mouse testes revealed by a novel mouse HSD3B1-specific rat monoclonal antibody.

Leydig cells play a pivotal function in the synthesis of a male sex steroid, testosterone. The ability of the steroid production is dependent on the expression of the steroidogenic genes, such as HSD3B (3ß-hydroxysteroid dehydrogenase/Δ5- Δ4 isomerase). It has been established that two different types of Leydig cells, fetal Leydig cells (FLCs) and adult Leydig cells (ALCs), are developed in mammalian testes. FLCs and ALCs are characterized by different sets of marker gene expression. In the case of mouse Leydig cells, Hsd3b1 (Hsd3b type 1) is expressed both in FLCs and ALCs whereas Hsd3b6 (Hsd3b type 6) is expressed in ALCs but not in FLCs. However, because the antibodies established so far for HSD3B were unable to distinguish between the HSD3B1 and HSD3B6 isoforms, it remained unclear whether both of them are expressed in every ALC. Therefore, in the present study, we generated a rat monoclonal antibody specific for mouse HSD3B1. Intriguingly, this monoclonal antibody together with an antibody specific for HSD3B6 identified three populations of ALCs based on the expression levels of these HSD3Bs.

Intramolecular Desulfitative Coupling: Nickel-Catalyzed Transformation of Diaryl Sulfones into Biaryls via Extrusion of SO2.

As a new transformation of organosulfur compounds, intramolecular desulfitative coupling of diaryl sulfones to the corresponding biaryls has been developed with the aid of nickel-NHC catalysts. This catalytic elimination of SO2 was also applicable to alkenyl aryl sulfone to furnish the corresponding alkenyl arene.