Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to N-Unprotected Ketimines: Efficient Synthesis of Cipargamin.

Highly enantioselective rhodium-catalyzed addition of arylboroxines to N-unprotected ketimines is realized for the first time by employing chiral BIBOP-type ligands with a Rh loading as low as 1 mol %. A range of chiral α-trifluoromethyl-α,α-diaryl α-tertiary amines or 3-amino-3-aryloxindoles were formed with excellent ee values and yields by employing either WingPhos or PFBO-BIBOP as the ligand. The method has enabled an efficient enantioselective synthesis of cipargamin.

Unexpected O-H Insertion of Rhodium-Azavinylcarbenes with N-Acylhydrazones: Divergent Synthesis of 3,6-Disubstituted- and 3,5,6-Trisubstituted-1,2,4-Triazines.

A practical and efficient method for divergent synthesis of 3,6-disubstituted- and 3,5,6-trisubstituted-1,2,4-triazines via unexpected rhodium-catalyzed O-H insertion/rearrangement/conditions-controlled intramolecular cyclization and oxidation reaction under mild conditions has been developed. Notably, it is the first example for the synthesis of 1,2,4-triazines with different substituted-patterns via a common intermediate with excellent chemoselectivities by the reaction of N-acylhydrazones as aze-[3C] or [4C] synthons with N-sulfonyl-1,2,3-triazoles as aze-[2C] synthons. Furthermore, this method allows direct access to di(het)aryl ketone frameworks containing 1,2,4-triazine moiety for the first time, serving as a versatile building block for the synthesis of other useful heterocyclic skeletons, such as pyridine or pyridazinone-fused triazine in excellent yields.

Highly Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram.

Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)-WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram.

Chiral N,O-Ligand/[Cu(OAc)2 ]-Catalyzed Asymmetric Construction of 4-Aminopyrrolidine Derivatives by 1,3-Dipolar Cycloaddition of Azomethine Ylides with α-Phthalimidoacrylates.

A protocol to access useful 4-aminopyrrolidine-2,4-dicarboxylate derivatives has been developed. A variety of chiral N,O-ligands derived from 2,3-dihydroimidazo[1,2-a]pyridine motifs have been evaluated in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides to α-phthalimidoacrylates. Reactions catalyzed by copper in combination with ligand 7-Cl-DHIPOH provided the highest level of stereoselectivity for the 1,3-dipolar cycloaddition reaction. The reaction tolerates both ß-substituted and ß-unsubstituted α-phthalimidoacrylate as dipolarophiles, affording the corresponding quaternary 4-aminopyrrolidine cycloadducts with excellent diastereo- (>98:2 d.r.) and enantioselectivities (up to 97 % ee). Removal of the phthalimido protecting group can be accomplished by a simple NaBH4 reduction. Theoretical calculations employing DFT methods show this cycloaddition reaction is likely to proceed through a stepwise mechanism and the stereochemistry was also theoretically rationalized.

Kinetic resolution of α-methylene-ß-hydroxy esters catalyzed by acyl transfer catalyst An-PIQ.

A highly efficient nonenzymatic kinetic resolution of a series of structurally diverse racemic α-methylene-ß-hydroxy esters utilizing the acyl transfer catalyst An-PIQ and propionic anhydride is reported. This procedure provides recovered alcohols with extremely high ee's (up to >99%) in reasonable conversions and excellent selectivity factors (S up to 108). Several synthetically important substrates were resolved in gram-scale reactions, and highly optically pure α-methylene-ß-hydroxy esters were obtained with excellent S values and good yields.

Double carbometallation of alkynes: an efficient strategy for the construction of polycycles.

Cyclization reactions of alkynes, especially the double carbometallation of alkynes, have drawn much interest from organic chemists because of their high efficiency in the construction of polycycles. Utilizing different nucleophiles or catalytic systems, various efficient strategies to access challenging skeletons have been extensively explored in recent years. In this review, achievements in this field are presented in three major parts (the syn-syn, anti-anti, and syn-anti addition reactions of diynes or two alkyne molecules). Cyclization reactions of diynes initiated by nucleophiles, [2+2+n] cycloaddition, or other processes and reactions, involving two identical or different alkynes are described, which provide facile and reliable approaches to various π systems, medium-sized rings, and even macrocycles.

Silver(I) and copper(I) cocatalyzed tandem reaction of 2-alkynylbenzaldoximes with aldehydes or alcohols: approach to 4-carboxylated isoquinolines.

A novel and efficient route for the preparation of 4-carboxylated isoquinolines via a Ag(I) and Cu(I) cocatalyzed tandem reaction of 2-alkynylbenzaldoximes with aldehydes or alcohols in moderate to good yields is described. The reaction proceeds smoothly to produce C-N and C-O bonds in a one-pot procedure with structural complexity and molecular diversity.

Dissecting microenvironment in cystadenomas and hepatic cysts based on single nucleus RNA-sequencing data.

Hepatic cystadenoma is a rare disease, accounting for about 5% of all cystic lesions, with a high tendency of malignant transformation. The preoperative diagnosis of cystadenoma is difficult, and some cystadenomas are easily misdiagnosed as hepatic cysts at first. Hepatic cyst is a relatively common liver disease, most of which are benign, but large hepatic cysts can lead to pressure on the bile duct, resulting in abnormal liver function. To better understand the difference between the microenvironment of cystadenomas and hepatic cysts, we performed single-nuclei RNA-sequencing on cystadenoma and hepatic cysts samples. In addition, we performed spatial transcriptome sequencing of hepatic cysts. Based on nucleus RNA-sequencing data, a total of seven major cell types were identified. Here we described the tumor microenvironment of cystadenomas and hepatic cysts, particularly the transcriptome signatures and regulators of immune cells and stromal cells. By inferring copy number variation, it was found that the malignant degree of hepatic stellate cells in cystadenoma was higher. Pseudotime trajectory analysis demonstrated dynamic transformation of hepatocytes in hepatic cysts and cystadenomas. Cystadenomas had higher immune infiltration than hepatic cysts, and T cells had a more complex regulatory mechanism in cystadenomas than hepatic cysts. Immunohistochemistry confirms a cystadenoma-specific T-cell immunoregulatory mechanism. These results provided a single-cell atlas of cystadenomas and hepatic cyst, revealed a more complex microenvironment in cystadenomas than in hepatic cysts, and provided new perspective for the molecular mechanisms of cystadenomas and hepatic cyst.

Synthesis of pyrazolo[5,1-a]isoquinolines via silver(I)-rhodium(I) cooperative catalysis in the reaction of N'-(2-alkynylbenzylidene)hydrazide with cycloprop-2-ene-1,1-dicarboxylate.

A tandem reaction between N'-(2-alkynylbenzylidene)hydrazide and cycloprop-2-ene-1,1-dicarboxylate co-catalyzed by silver triflate and tris(triphenylphosphine)rhodium chloride is reported. The reaction proceeds through 6-endo-cyclization, [3 + 2] cycloaddition, cyclopropane opening, and aromatization, leading to pyrazolo[5,1-a]isoquinolines in moderate to good yields.

Silver triflate-catalyzed tandem reaction of N'-(2-alkynylbenzylidene)hydrazide with pyridyne.

A silver triflate-catalyzed tandem reaction of N'-(2-alkynylbenzylidene)hydrazide with pyridyne is presented. Different outcomes are obtained, depending on the pyridynes utilized in the transformation.

An efficient approach to pyrazolo[5,1-a]isoquinolin-2-amines via a silver(I)-catalyzed three-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, and nitrile.

A three-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, and nitrile catalyzed by silver triflate under mild conditions is reported, which generates pyrazolo[5,1-a]isoquinolin-2-amines in good to excellent yields.

Risk factors for hepatic insufficiency after major hepatectomy in non-cirrhotic patients.

It is very necessary for patients with liver cancer to reasonably apply the prediction method of liver failure after hepatectomy before liver surgery. Liver surgeons can benefit greatly from clinical activities.

Synthesis of 1-(1H-indol-3-yl)-1,2-dihydroisoquinolines via AgOTf-catalyzed three-component reactions of 2-alkynylbenzaldehydes, amines, and indoles.

Three-component reactions of 2-alkynylbenzaldehydes, amines, and indoles catalyzed by AgOTf under mild conditions afford the 1-(1H-indol-3-yl)-1,2-dihydroisoquinolines in good yields. This silver-catalyzed tandem reaction is found to be workable with various indoles, anilines or alkyl amines, and 2-alkynylbenzaldehydes with electron-withdrawing groups attached on the aromatic backbone.

Tandem reactions of N'-(2-alkynylbenzylidene)hydrazides with silyl enolates: a facile route to H-pyrazolo[5,1-a]isoquinolines.

A silver triflate-catalyzed tandem reaction of N'-(2-alkynylbenzylidene)hydrazide with silyl enolate is described, which generates the unexpected H-pyrazolo[5,1-a]isoquinolines in good to excellent yields. Intramolecular cyclization, nucleophilic addition, condensation, and aromatization may be involved in the reaction process.

Generation of diverse 2H-isoindol-1-ylphosphonates via three-component reaction of 2-alkynylbenzaldehyde, aniline, and phosphite.

Diverse 2H-isoindol-1-ylphosphonates as potential HCT-116 inhibitors are easily generated via a FeCl(3) and PdCl(2) cocatalyzed three-component reaction of 2-alkynylbenzaldehyde, aniline, and phosphite. The focused small library is constructed based on parallel diversity-oriented synthesis.

[Assessment of cerebral oxygen saturation using near infrared spectroscopy under driver fatigue state].

The objective of the present study is to assess the cerebral saturation under driver fatigue based on the near infrared spectroscopy (NIRS) signals. Twenty healthy male subjects were randomly divided into two groups: A-group (study group) and B-group (control group). All subjects were required to be well rested before the experiment. In A-group the subjects were required to perform the simulated driving task for 3 hours. Cerebral oxygenation signal was monitored for 20 minutes prior to and after the prescribed task period from the left frontal lobe. The results show that cerebral oxygen saturation was found to be significantly lower following 3-hour driving in the task group compared to that in the control group (F = 15.92, p < 0.001). Also a significant difference in selective reaction time was observed between the task group and control group during the post task period (p = 0.021). These findings showed that the cerebral blood oxygen saturation was closely related to the driver fatigue. The decline of the cerebral oxygen saturation might indicate a reduced cerebral oxygen delivery. This suggests that NIRS could provide a non-invasive method to detect driver fatigue.

Multicatalytic tandem reaction of N'-(2-alkynylbenzylidene)hydrazide with indole.

The combination of AgOTf and Dy(OTf)(3) shows high efficiency as a catalyst in the tandem reactions of N'-(2-alkynylbenzylidene)hydrazides with indoles, which generate the unexpected 1-(indol-3-yl)-2-aminoisoquinolinium triflates in good yields.

Synthesis of functionalized H-pyrazolo[5,1-a]isoquinolines via sequential reactions of N'-(2-alkynylbenzylidene)hydrazides.

Diversity-oriented synthesis of functionalized H-pyrazolo[5,1-a]isoquinolines via sequential reactions of N'-(2-alkynylbenzylidene)hydrazide is described. Bromine-mediated electrophilic cyclization, Ag-catalyzed alkyne nucleophilic addition, and palladium-catalyzed cross-coupling reaction were involved in the transformation.

Synthesis of functionalized isoquinolines via sequential cyclization/cross-coupling reactions.

CuX(2)-mediated cyclization of 2-alkynylbenzaldehyde O-methyl oximes in N,N-dimethylacetamide (DMA) gave rise to 4-chloroisoquinolines in good yield, which underwent the palladium-catalyzed cross-coupling reactions of arylboronic acids subsequently to afford the functionalized isoquinolines.

Assessment of cerebral oxygenation during prolonged simulated driving using near infrared spectroscopy: its implications for fatigue development.

Information on cerebral oxygenation during prolonged driving in healthy humans may help to explain the cause and development of central fatigue and its effects on cortex activities. The objective of this study is to investigate the time course of cerebral oxygenation during a prolonged driving task. Forty healthy male subjects were randomly divided into two groups: task group (Task) and control group (CNL). All subjects were required to rest well prior to the experiment. For the task group, subjects were required to perform the simulated driving task for 3 h. Cerebral oxygenation signal was monitored from the left frontal lobe using near infrared spectroscopy throughout the entire experiment. Significant increases in the concentrations of HbO(2) (DeltaCHbO(2)) and HbT (DeltaCHbT) were recorded at the start of driving task compared with the resting value (p < 0.01). The cerebral oxygen saturation in the Task group was found to be significantly lower following three hours of driving compared with that in the CNL (F = 16.95, p < 0.001). In addition, a significant difference in selective reaction time was observed between the Task group and CNL during the post-task period (p = 0.023). The results demonstrated that the cerebral oxygenation is closely related to the mental stress. The decrease in the cerebral oxygen saturation may indicate reduced cerebral oxygen delivery, and this may be an important factor affecting central fatigue development during prolonged driving.