Ruthenium-Catalyzed Enantioselective Hydrogenation of 9-Phenanthrols.

The enantioselective hydrogenation of arenols to corresponding chiral cyclic alcohols remains a challenge because of their aromaticity and the difficulty in controlling the regio-, chemo-, and stereoselectivity. In this work, the first highly efficient ruthenium-catalyzed enantioselective hydrogenation of 9-phenanthrols has been successfully realized under mild conditions via trapping the unstable keto tautomers. The method provides a facile access to a range of chiral 9,10-dihydrophenanthren-9-ols with up to 98 % yield and >99 % ee. The hydrogenation pathway includes base-promoted tautomerization of 9-phenanthrols and Ru-catalyzed asymmetric hydrogenation of the in situ generated unstable keto tautomers.

[Q-markers of Yuquan Capsules based on serum pharmacochemistry of Chinese medicine].

This study analyzed the quality markers(Q-markers) of Yuquan Capsules(YQC) based on serum pharmacochemistry of Chinese medicine and detected the components and metabolites of YQC absorbed into the blood by UPLC-Q-TOF-MS and UNIFI systems. As a result, 32 components of YQC were detected, including 17 prototype components and 15 metabolized components. Among them, 12 prototype components(ginsenoside Rh_2, genistein, formononetin, puerarin, daidzein, schizandrin A, schizandrin B, schizandrin C, schizandrol A, schizandrol B, gomisin D, and ononin) and 12 metabolized components(ginsenoside Rg_1, ginsenoside Rg_2, ginsenoside Rg_3, ginsenoside Ro, 3'-methoxypuerarin, daidzin, astragaloside Ⅱ, astragaloside Ⅳ, glycyrrhizic acid, liquiritigenin, isoliquiritin, and verbascoside) showed inhibitory effects and pharmacological activities against diabetes, and these 24 blood-entering components against diabetes were identified as Q-markers of YQC.

Manganese-Catalyzed Asymmetric Formal Hydroamination of Allylic Alcohols: A Remarkable Macrocyclic Ligand Effect.

A unique family of chiral peraza N6 -macrocyclic ligands, which are conformationally rigid and have a tunable saddle-shaped cavity, is described. Utilizing their manganese(I) complexes, the first example of earth-abundant transition metal-catalyzed asymmetric formal anti-Markovnikov hydroamination of allylic alcohols was realized, providing a practical access to synthetically important chiral γ-amino alcohols in excellent yields and enantioselectivities (up to 99 % yield and 98 % ee). The single-crystal structure of a MnI complex indicates that the manganese atom coordinates with the chiral dialkylamine moiety in a bidentate fashion. Further DFT calculations revealed that five of the six nitrogen atoms in the ligand were engaged in multiple noncovalent interactions with Mn, an isopropanol molecule, and a ß-amino ketone intermediate via coordination, hydrogen bonding, and/or CH⋅⋅⋅π interactions in the transition state, showing a remarkable role of the macrocyclic framework.

Rhodium-Catalyzed ON-OFF Switchable Hydrogenation Using a Molecular Shuttle Based on a [2]Rotaxane with a Phosphine Ligand.

A novel pH-responsive molecular shuttle based on a [2]rotaxane with a phosphine ligand has been designed and synthesized. In the rhodium-catalyzed hydrogenation of α,ß-dehydroamino acid esters and aryl enamides, ON/OFF-switchable catalysis was accomplished with high ON/OFF ratios by adjusting the movements of the rotaxane wheels located at the catalyst terminals with acid/base. Mechanistic studies using NMR spectroscopy and quasi in situ X-ray photoelectron spectroscopy revealed that RhIII -hydride species are possibly formed in a H2 atmosphere when the catalyst is in the OFF state. During the reaction, a heterolytic activation of dihydrogen occurs by the interlocked rotaxane dibenzylamine and RhI catalytic center acting as a frustrated Lewis pair. Subsequent homolytic splitting of dihydrogen with the newly formed RhI -hydride species generates RhIII -hydride species. These findings show that a substrate-selective hydrogenation can be achieved by using the OFF-state catalyst.

Asymmetric Ruthenium-Catalyzed Hydrogenation of Terpyridine-Type N-Heteroarenes: Direct Access to Chiral Tridentate Nitrogen Ligands.

The first enantioselective hydrogenation of terpyridine-type N-heteroarenes has been successfully developed by using Ru(diamine) complexes as catalysts, providing partially reduced chiral pyridine-amine-type products in high yield (up to 93%) with excellent diastereo- and enantioselectivity (up to 94:6 dl/meso, > 99% ee). These pyridine-amine-type compounds can be served as a new class of chiral multidentate nitrogen-donor ligands, which were successfully applied to the Cu-catalyzed asymmetric Friedel-Crafts alkylation reaction of indoles with nitroalkenes.

Ovarian endometrioid carcinoma resembling sex cord-stromal tumor: A case report.

BACKGROUND: Ovarian endometrioid carcinoma resembling sex cord-stromal tumor (ECSCSs) is rare. CASE SUMMARY: We present a rare case of primary ECSCSs in the left ovary. A 39-year-old female patient had persistent dull pain in the lower abdomen for more than 1 mo, and she was initially diagnosed with pelvic inflammatory disease at a hospital. The patient received transabdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymph node dissection at our hospital and finally diagnosed with ECSCSs. After the operation, the patient received eight courses of cisplatinum + etoposide + bleomycin chemotherapy treatment and no evidence of tumor recurrence or metastasis was found in a 2-year follow-up period. CONCLUSION: Ovarian endometrioid carcinoma is similar to the ovary sex cord-stromal tumor, especially when the cord-like structure is obvious. The clinical diagnosis for this tumor is difficult before surgery and pathology examination. The necessary immunohistochemical markers are of positive significance for assisting diagnosis and differential diagnosis.

Diaza-Crown Ether-Bridged Chiral Diphosphoramidite Ligands: Synthesis and Applications in Asymmetric Catalysis.

A small library of diaza-crown ether-bridged chiral diphosphoramidite ligands was prepared. In the rhodium-catalyzed asymmetric hydrogenation and hydroformylation reactions, these ligands exhibited distinct properties in catalytic activity and/or enantioselectivity. Hydrogenated products with opposite absolute configurations could be obtained in high yields with excellent ee values by utilizing (S,S)-L1 and (S,S)-L3, respectively. Meanwhile, the addition of alkali metal cations caused variations in catalytic outcomes, showing the supramolecular tunability of these Rh/diphosphoramidite catalytic systems.

Highly Enantioselective Ruthenium-Catalyzed Cascade Double Reduction Strategy: Construction of Structurally Diverse Julolidines and Their Analogues.

A direct and facile construction of optically pure julolidine derivatives through ruthenium-catalyzed enantioselective cascade hydrogenation and reductive amination of 2-(quinolin-8-yl)ethyl ketones has been developed. By means of this protocol, various chiral julolidine compounds were obtained in high isolated yields (up to 94%) with excellent diastereoselectivities (up to >20:1 dr) and enantioselectivities (up to 99% ee) under mild conditions. Furthermore, the synthetic practicality of this protocol was illustrated by the preparation of hexahydrojulolidines and a chiral fluorescent molecular rotor.

Consecutive Intermolecular Reductive Amination/Asymmetric Hydrogenation: Facile Access to Sterically Tunable Chiral Vicinal Diamines and N-Heterocyclic Carbenes.

A highly enantioselective iridium- or ruthenium-catalyzed intermolecular reductive amination/asymmetric hydrogenation relay with 2-quinoline aldehydes and aromatic amines has been developed. A broad range of sterically tunable chiral N,N'-diaryl vicinal diamines were obtained in high yields (up to 95 %) with excellent enantioselectivity (up to >99 % ee). The resulting chiral diamines could be readily transformed into sterically hindered chiral N-heterocyclic carbene (NHC) precursors, which are otherwise difficult to access. The usefulness of this synthetic approach was further demonstrated by the successful application of one of the chiral vicinal diamines and chiral NHC ligands in a transition-metal-catalyzed asymmetric Suzuki-Miyaura cross-coupling reaction and asymmetric ring-opening cross-metathesis, respectively.

Asymmetric Hydrogenation of Dibenzo[c,e]azepine Derivatives with Chiral Cationic Ruthenium Diamine Catalysts.

An efficient Ru-catalyzed asymmetric hydrogenation of dibenzo[c,e]azepines is reported. A series of seven-membered cyclic amines were obtained with moderate to excellent enantioselectivity. The catalyst counteranion played an important role in achieving high-level chiral induction. Moreover, a one-pot synthesis of chiral 6,7-dihydro-5H-dibenz[c,e]azepines via two-step reductive amination was also developed.

Enantioselective synthesis of tunable chiral pyridine-aminophosphine ligands and their applications in asymmetric hydrogenation.

A small library of tunable chiral pyridine-aminophosphine ligands were enantioselectively synthesized based on chiral 2-(pyridin-2-yl)-substituted 1,2,3,4-tetrahydroquinoline scaffolds, which were obtained in high yields and with excellent enantioselectivities via ruthenium-catalyzed asymmetric hydrogenation of 2-(pyridin-2-yl)quinolines. The protocol features a wide substrate scope and mild reaction conditions, enabling scalable synthesis. These chiral P,N ligands were successfully applied in the Ir-catalyzed asymmetric hydrogenation of benchmark olefins and challenging seven-membered cyclic imines including benzazepines and benzodiazepines. Excellent enantio- and diastereoselectivity (up to 99% ee and >20 : 1 dr), and/or unprecedented chemoselectivity were obtained in the asymmetric hydrogenation of 2,4-diaryl-3H-benzo[b]azepines and 2,4-diaryl-3H-benzo[b][1,4]diazepines.

Genome-Wide Profiling of Long Noncoding RNA Expression Patterns in Women With Repeated Implantation Failure by RNA Sequencing.

OBJECTIVES: To compare long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression levels in endometrium between patients with repeated implantation failure (RIF) following in vitro fertilization (IVF)-embryo transfer and control women. MATERIALS AND METHODS: RNA sequencing (RNA-seq) and alignments were performed to identify lncRNAs and mRNAs using endometrial samples collected from 3 patients and 3 control women. A subset of 10 differentially expressed lncRNAs and 6 mRNAs were validated in all participants using quantitative reverse transcription polymerase chain reaction. The potential biological roles of identified lncRNAs were predicted via coexpressed mRNA annotations. Twenty patients with RIF and 30 control women were recruited for validation. RESULTS: We identified 1202 differentially expressed genes, including 742 lncRNAs and 460 mRNAs, in mid-secretory phase endometrial tissue from patients with RIF following IVF compared to control women. We analyzed the target genes of the lncRNAs and uncovered 148 lncRNAs corresponding to 147 cis-regulated target genes. The cis-regulated target genes of these significantly differentially expressed lncRNAs were clustered into several pathways, such as the tumor necrosis factor signaling pathway, the Toll-like receptor signaling pathway, and the NF-kappa B (NF-κB) signaling pathway. CONCLUSION: Our study constitutes the first report on the investigation of the regulatory mechanisms of lncRNAs in endometrial receptivity in women experiencing RIF using RNA-seq. Our results provide a valuable candidate reservoir for future functional studies of lncRNAs.

Rapid Construction of Structurally Diverse Quinolizidines, Indolizidines, and Their Analogues via Ruthenium-Catalyzed Asymmetric Cascade Hydrogenation/Reductive Amination.

A rapid construction of enantioenriched benzo-fused quinolizidines, indolizidines, and their analogues by ruthenium-catalyzed asymmetric cascade hydrogenation/reductive amination of quinolinyl- and quinoxalinyl-containing ketones has been developed. This reaction proceeds under mild reaction conditions, affording chiral benzo-fused aliphatic N-heterocyclic compounds with structural diversity in good yields (up to 95 %) with excellent diastereoselectivity (up to >20:1 dr) and enantioselectivity (up to >99 % ee). Furthermore, this catalytic protocol is applicable to the formal synthesis of (+)-gephyrotoxin.

Asymmetric Hydrogenation of In†Situ Generated Isochromenylium Intermediates by Copper/Ruthenium Tandem Catalysis.

The first asymmetric hydrogenation of in situ generated isochromenylium derivatives is enabled by tandem catalysis with a binary system consisting of Cu(OTf)2 and a chiral cationic ruthenium-diamine complex. A range of chiral 1H-isochromenes were obtained in high yields with good to excellent enantioselectivity. These chiral 1H-isochromenes could be easily transformed into isochromanes, which represent an important structural motif in natural products and biologically active compounds. The chiral induction was rationalized by density functional theory calculations.

Highly Enantioselective Direct Synthesis of Endocyclic Vicinal Diamines through Chiral Ru(diamine)-Catalyzed Hydrogenation of 2,2'-Bisquinoline Derivatives.

An asymmetric hydrogenation of 2,2'-bisquinoline and bisquinoxaline derivatives, catalyzed by chiral cationic ruthenium diamine complexes, was developed. A broad range of chiral endocyclic vicinal diamines were obtained in high yields with excellent diastereo- and enantioselectivity (up to 93:7 dl/meso and >99 % ee). These chiral diamines could be easily transformed into a new class of chiral N-heterocyclic carbenes (NHCs), which are important but difficult to access.

Asymmetric Hydrogenation of Quinoline Derivatives Catalyzed by Cationic Transition Metal Complexes of Chiral Diamine Ligands: Scope, Mechanism and Catalyst Recycling.

This personal account is focused on the asymmetric hydrogenation of quinolines and their analogues recently developed by using phosphorus-free chiral cationic ruthenium(II)/η6 -arene-N-monosulfonylated diamine complexes. In our initial study, the chiral Ru-diamine complexes were found to be highly effective catalysts for the asymmetric hydrogenation of difficult quinoline substrates in room temperature ionic liquids (RTILs) with unprecedentedly excellent enantioselectivity. Our further systematic study revealed that a wide range of quinoline derivatives could be efficiently hydrogenated in alcoholic solvents, or under solvent-free and concentrated conditions with good to excellent stereoselectivity. Complexes of iridium analogues could also efficiently catalyze the asymmetric hydrogenation of quinolines in undegassed solvent. Asymmetric tandem reduction of various 2-(aroylmethyl)quinolines was achieved in high yield with excellent enantioselectivity and good diastereoselectivity. More challenging substrates, alkyl- and aryl-substituted 1,5- and 1,8-naphthyridine derivatives were successfully hydrogenated with these chiral ruthenium catalysts to give 1,2,3,4-tetrahydronaphthyridines with good to excellent enantioselectivity. Unlike the asymmetric hydrogenation of ketones, quinoline is reduced via a stepwise H+ /H- transfer process outside the coordination sphere rather than a concerted mechanism. The enantioselectivity originates from the CH/π attraction between the η6 -arene ligand in the Ru-complex and the fused phenyl ring of dihydroquinoline via a 10-membered ring transition state with the participation of TfO- anion. In addition, the Ru-catalyzed asymmetric hydrogenation of quinolines could be carried out in some environmentally benign reaction media, such as undegassed water, RTILs and oligo(ethylene glycol)s (OEGs). In the latter two cases, unique chemoselectivity and/or reactivity were observed. Catalyst recycling could also be realized by using [BMIM]PF6 and OEGs as solvents, as well as via magnetic nanoparticles. Applications of this catalytic protocol were also exemplified by the employments of the reduced products for the syntheses of some important natural alkaloids, pharmaceutical intermediates, as well as chiral diamine ligands.

From Weakness to Strength: C-H/π-Interaction-Guided Self-Assembly and Gelation of Poly(benzyl ether) Dendrimers.

The C-H/π interactions as the key driving force for the construction of supramolecular gels remain a great challenge because of their weak nature. We hereby employed for the first time weak C-H/π interactions for the construction of supramolecular dendritic gels based on peripherally methyl-functionalized poly(benzyl ether) dendrimers. Their gelation property is highly dependent on the nature of the peripheral methyl groups. Furthermore, single-crystal X-ray analysis and NMR spectroscopy revealed that multiple C-H/π interactions between the proton of the methyl group and the electron-rich peripheral methyl-substituted aryl ring played significant roles in the formation of supramolecular nanofibers and organogels. This study uncovers the critical role of weak noncovalent interactions and provides new insights into the further design of self-assembled nanomaterials.

Solvent-Regulated Asymmetric Hydrogenation of Quinoline Derivatives in Oligo(Ethylene Glycol)s through Host-Guest Interactions.

The asymmetric hydrogenation of quinolines in oligo(ethylene glycol)s (OEGs) and poly(ethylene glycol)s (PEGs) with chiral cationic ruthenium diamine complexes has been investigated. Interestingly, in liquid PEGs or long-chain OEGs, the Ru catalysts lost their reactivity. Upon the addition of a little MeOH, the hydrogenation of quinoline was switched "ON". Evidence from mass spectrometry and control experiments revealed that encapsulation of the quinolinium salt by PEG or long-chain OEG molecules through supramolecular interactions is possibly the main reason for such a switchable hydrogenation reaction. Moreover, the asymmetric hydrogenation of 2-substituted quinoline derivatives was achieved in triethylene glycol (3-OEG), thereby affording 1,2,3,4-tetrahydroquinolines with excellent reactivities and enantioselectivities (up to 99 % ee). Furthermore, the Ru catalyst could be readily recycled for both pure 3-OEG and biphasic 3-OEG/n-hexane systems without a clear loss of reactivity and enantioselectivity.

Ruthenium-Catalyzed Enantioselective Hydrogenation of 1,8-Naphthyridine Derivatives.

The first asymmetric hydrogenation of 2,7-disubstituted 1,8-naphthyridines catalyzed by chiral cationic ruthenium diamine complexes has been developed. A wide range of 1,8-naphthyridine derivatives were effectively hydrogenated to give 1,2,3,4-tetrahydro-1,8-naphthyridines with up to 99% ee and full conversions. The method provides a practical and facile approach to the preparation of valuable chiral heterocyclic building blocks and useful motifs for a new kind of P,N-ligand.

Asymmetric Hydrogenation of α-Purine Nucleobase-Substituted Acrylates with Rhodium Diphosphine Complexes: Access to Tenofovir Analogues.

The first asymmetric hydrogenation of α-purine nucleobase-substituted α,ß-unsaturated esters, catalyzed by a chiral rhodium (R)-Synphos catalyst, has been developed. A wide range of mono- and disubstituted acrylates were successfully hydrogenated under very mild conditions in high yields with good to excellent enantioselectivities (up to 99% ee). This method provides a convenient approach to the synthesis of a new kind of optically pure acyclic nucleoside and Tenofovir analogues.