Substrate-directed divergent annulations of sulfur ylides: synthesis of functionalized bispirocyclopentane and bispirocyclopropane derivatives.

Herein, an efficient, substrate-directed divergent [2 + 3]/[2 + 1] annulation of tetra-substituted oxa-dienes and allylic sulfur ylides has been successfully developed. Under precise annulation regulation, a series of functionalized bispirocyclopentane and bispirocyclopropane derivatives were synthesized in a highly stereoselective and economical manner (up to 95% yield, >20 : 1 dr or >20 : 1 E/Z). This protocol offers the advantages of mild conditions, high chemo-, regio- and diastereoselectivity and broad substrate compatibility. In addition, the synthetic practicality of this protocol was evaluated through a scale-up preparation and a series of three-component reactions utilizing in situ generated sulfur ylides.

COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.

Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.

Catalytic Asymmetric [8+2] Annulation Reactions Promoted by a Recyclable Immobilized Isothiourea.

Higher-order cycloaddition reactions constitute an efficient approach towards the construction of medium to large ring systems. However, enantioselective versions of these transformations remain scarce, which hampers their deployment in medicinal chemistry, or any other discipline in which homochirality is deemed crucial. Herein, we report a novel method for the production of enantiomerically enriched cycloheptatrienes fused to a pyrrolidone ring on the basis of an isothiourea-catalyzed periselective [8+2] cycloaddition reaction between chiral ammonium enolates (generated in situ from carboxylic acids) and azaheptafulvenes. The resulting bicyclic compounds can be hydrogenated, but, most remarkably, they can also undergo completely regioselective [4+2] cycloaddition with active dienophiles to give architecturally complex polycyclic compounds in a straightforward manner.

Highly enantioselective cross-aldol reactions of acetaldehyde mediated by a dual catalytic system operating under site isolation.

Polystyrene-supported (PS) diarylprolinol catalysts 1 a (Ar = phenyl) and 1 b (Ar = 3,5-bis(trifluoromethyl)phenyl) have been developed. Operating under site-isolation conditions, PS-1 a/1 b worked compatibly with PS-bound sulfonic acid catalyst 2 to promote deoligomerization of paraldehyde and subsequent cross-aldol reactions of the resulting acetaldehyde in one pot, affording aldol products in high yields with excellent enantioselectivities. The effect of water on the performance of the catalytic system has been studied and its optimal amount (0.5 equiv) has been determined. The dual catalytic system (1/2) allows repeated recycling and reuse (10 cycles). The potential of this methodology is demonstrated by a two-step synthesis of a phenoperidine analogue (68% overall yield; 98% ee) and by the preparation of highly enantioenriched 1,3-diols 4 and 3-methylamino-1-arylpropanols 5, key intermediates in the synthesis of a variety of druglike structures.

Key candidate genes and pathways in T lymphoblastic leukemia/lymphoma identified by bioinformatics and serological analyses.

T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL) is an uncommon but highly aggressive hematological malignancy. It has high recurrence and mortality rates and is challenging to treat. This study conducted bioinformatics analyses, compared genetic expression profiles of healthy controls with patients having T-ALL/T-LBL, and verified the results through serological indicators. Data were acquired from the GSE48558 dataset from Gene Expression Omnibus (GEO). T-ALL patients and normal T cells-related differentially expressed genes (DEGs) were investigated using the online analysis tool GEO2R in GEO, identifying 78 upregulated and 130 downregulated genes. Gene Ontology (GO) and protein-protein interaction (PPI) network analyses of the top 10 DEGs showed enrichment in pathways linked to abnormal mitotic cell cycles, chromosomal instability, dysfunction of inflammatory mediators, and functional defects in T-cells, natural killer (NK) cells, and immune checkpoints. The DEGs were then validated by examining blood indices in samples obtained from patients, comparing the T-ALL/T-LBL group with the control group. Significant differences were observed in the levels of various blood components between T-ALL and T-LBL patients. These components include neutrophils, lymphocyte percentage, hemoglobin (HGB), total protein, globulin, erythropoietin (EPO) levels, thrombin time (TT), D-dimer (DD), and C-reactive protein (CRP). Additionally, there were significant differences in peripheral blood leukocyte count, absolute lymphocyte count, creatinine, cholesterol, low-density lipoprotein, folate, and thrombin times. The genes and pathways associated with T-LBL/T-ALL were identified, and peripheral blood HGB, EPO, TT, DD, and CRP were key molecular markers. This will assist the diagnosis of T-ALL/T-LBL, with applications for differential diagnosis, treatment, and prognosis.

Enantioselective metal/organo-catalyzed aerobic oxidative sp3 C-H olefination of tertiary amines using molecular oxygen as the sole oxidant.

An organocatalysis/copper-catalyzed asymmetric oxidative sp(3) C-H olefination reaction of tertiary amines with olefins using molecular oxygen as the sole oxidant under mild conditions was realized for the first time. This novel strategy provides an efficient and environmentally friendly way to access diversify optically active C(1)-alkene tetrahydroisoquinoline derivatives.

One-pot enantioselective synthesis of functionalized pyranocoumarins and 2-amino-4H-chromenes: discovery of a type of potent antibacterial agent.

Function-oriented design and synthesis of chiral small molecules with novel activity is a key goal in modern organic chemistry. As multiple antibiotic-resistant pathogens are emerging and causing serious diseases, the need for practical routes for the development of new types of antibacterial agents is very urgent. Herein, we present a highly efficient process for the synthesis of optically active pyranocoumarins and 2-amino-4H-chromenes through an organocatalytic Knoevenagel/Michael/cyclization sequence, and the preliminary biological studies of these new heterocyclic compounds revealed potent antibacterial activity. This study provides a novel strategy for further research and development of new types of antibacterial agents effective against human pathogens.

Comparative analysis of three serum-free light-chain detection systems in the diagnosis of multiple myeloma.

OBJECTIVE: To observe the comparability of serum-free light chain (sFLC) detected by Beckman, Siemens, and Binding Site. METHODS: In this study, 110 patients who were diagnosed with multiple myeloma in State Key Laboratory of Experimental Hematology from November 2019 to August 2020. According to the instructions of equipment and reagent manufacturers, three detection systems (Binding Site, Beckman, and Siemens) were used to detect the serum-free light chain of selected analysis samples. Meanwhile, sFLC test results of the three instruments were compared. According to EP9-A3 guide, correlation and consistency were conducted by Bland-Altman and Passing-Bablok regression. RESULTS: The free kappa light-chain serum samples and the free lambda light-chain samples were quantitatively analyzed by the three systems. Binding Site, Beckman, and Siemens free light-chain detection results were as follows: FLC-κ: 42.23 (3.73, 423), 34.55 (6.5, 194), 39.85 (3.73, 423); FLC-λ: 31.46 (1.39, 8180.42), 32 (4.3, 275), 37.65 (2.28, 526); rFLC (FLC-κ/FLC-λ): 1.21 (0, 131.28), 0.96 (0.02, 43.49), 1.04 (0.04, 40.29). The Kappa valuation of FLC-κ between Beckman and Binding Site is 0.97, Kappa valuation of FLC-λ between Beckman and Binding Site is 0.96, Kappa valuation of rFLC between Beckman and Binding Site is 0.97. The Kappa valuation of FLC-κ between Siemens and Binding Site is 0.96, Kappa valuation of FLC-λ between Siemens and Binding Site is 0.88, Kappa valuation of rFLC between Siemens and Binding Site is 0.94. CONCLUSION: All of the three systems can meet the needs of diagnosis and treatment in clinical application. These analyses showed a very good concordance between Beckman, Siemens, and Binding Site.

[Two Serum Free Light Chain Detection Systems in the Diagnosis of Multiple Myeloma].

OBJECTIVE: To investigate the comparability of the Freelite, Binding Site, Beckman and N Latex FLC, Siemens in the detection of serum free light chain (sFLC) . METHODS: Fifty newly diagnosed multiple myeloma (MM) patients in Tianjin Institute of Blood Research from November 2019 to February 2020 were enrolled. The two systems (Freelite, Binding Site, Beckman and N Latex FLC, Siemens) were used to detect the sFLC of the samples. Outlier detection was performed by ESD method, methodological comparison and deviation assessment were performed by Passing-Bablok regression and Bland-Altman regression. RESULTS: Both the systems could quantitatively analyze free kappa light chain serum samples and free lambda light chain samples. Freelite, Binding Site, Beckman and N Latex FLC, Siemens free light chain test showed FLC-κ：36.5 (6.5, 194), 40.5 (6.94, 288), FLC-λ: 30.1 (4.3, 170.5), 35.1 (2.28, 526), rFLC (FLC-κ/ FLC-λ) : 0.82 (0.05, 43.25), 1.03 (0.03, 32.04), dFLC (｜FLC-κ- FLC-λ｜) : -5.8 (-161.97, 183.7), 1.1 (-505.1, 279.01), which existed no outliers. There were systematic differences, and the deviation level was not within the clinically acceptable range. CONCLUSION: Both the systems can meet the needs of clinical diagnosis and treatment, but there is a significant deviation between the two systems, the results are not comparable, and should be analyzed separately. In particular, the same system should be selected for monitoring the prognosis of MM.

Diastereodivergent Enantioselective [8 + 2] Annulation of Tropones and Enals Catalyzed by N-Heterocyclic Carbenes.

N-Heterocyclic carbene catalysts are used for the first time to mediate asymmetric [8 + 2] cycloadditions of enals with tropones. The kinetic [8 + 2] cis-cycloadducts can be epimerized to their trans analogues by simply using increased amounts of base and longer reaction times. Substituted tropones are also tolerated, and the cycloaddition products can be derivatized by hydrogenation or methanolysis. The main stereochemical features of the process have been rationalized by microkinetic modeling based on the results of DFT calculations.

Synthesis of Diverse 11- and 12-Membered Macrolactones from a Common Linear Substrate Using a Single Biocatalyst.

The diversification of late stage synthetic intermediates provides significant advantages in efficiency in comparison to conventional linear approaches. Despite these advantages, accessing varying ring scaffolds and functional group patterns from a common intermediate poses considerable challenges using existing methods. The combination of regiodivergent nickel-catalyzed C-C couplings and site-selective biocatalytic C-H oxidations using the cytochrome P450 enzyme PikC addresses this problem by enabling a single late-stage linear intermediate to be converted to macrolactones of differing ring size and with diverse patterns of oxidation. The approach is made possible by a novel strategy for site-selective biocatalytic oxidation using a single biocatalyst, with site selectivity being governed by a temporarily installed directing group. Site selectivities of C-H oxidation by this directed approach can overcome positional bias due to C-H bond strength, acidity, inductive influences, steric accessibility, or immediate proximity to the directing group, thus providing complementarity to existing approaches.

H-Bond-Directing Organocatalyst for Enantioselective [4 + 2] Cycloadditions via Dienamine Catalysis.

An efficient, highly regio- and stereoselective [4 + 2] cycloaddition reaction to generate tetrahydropyranopyrazole frameworks has been developed. To this end, a dienamine-based catalytic strategy that relies on the H-bond-directing effect of the hydroxy group of a dinaphthylprolinol-type aminocatalyst has been used. This enables the synthesis of multifunctionalized heterocyclic derivatives with three contiguous stereocenters in good yields and excellent enantioselectivities.

An asymmetric approach toward chiral multicyclic spirooxindoles from isothiocyanato oxindoles and unsaturated pyrazolones by a chiral tertiary amine thiourea catalyst.

The first organocatalytic Michael-cyclization cascade reaction between isothiocyanato oxindoles and unsaturated pyrazolones has been developed. The multicyclic spiro[oxindole/thiobutyrolactam/pyrazolone] core structures containing three contiguous stereogenic centers, including two spiro quaternary centers, were prepared with excellent diastereo- (up to >20 : 1) and enantioselectivities (up to 99% ee).

Highly enantioselective Friedel-Crafts alkylation reaction catalyzed by rosin-derived tertiary amine-thiourea: synthesis of modified chromanes with anticancer potency.

We present herein for the first time the synthesis and preliminary biological evaluation of various modified chromanes via a rosin-derived tertiary amine-thiourea-catalyzed highly enantioselective Friedel-Crafts alkylation reaction.

PPh3-catalyzed synthesis of dicyano-2-methylenebut-3-enoates as efficient dienes in catalytic asymmetric inverse-electron-demand Diels-Alder reaction.

We present here the synthesis of dicyano-2-methylenebut-3-enoates as novel Diels-Alder dienes through an efficient PPh(3)-catalyzed strategy, and an unprecedented PPh(3)-catalyzed addition/all-carbon-based asymmetric inverse-electron-demand Diels-Alder sequence reaction is disclosed for the first time.