Catalyst-Free Synthesis of Polycyclic Spiroindolines by Cascade Reaction of 3-(2-Isocyanoethyl)indoles with 1-Sulfonyl-1,2,3-triazoles.

A catalyst-free cascade reaction of 3-(2-isocyanoethyl)indoles and 1-sulfonyl-1,2,3-triazoles was realized. This dearomative spirocyclization provided an efficient protocol to synthesize a series of polycyclic indolines bearing spiro-α-carboline in moderate to high yields in one step under thermal reaction conditions.

Synthesis of 3-aminoquinolines from α-imino rhodium carbenes and 2-aminobenzaldehydes.

A facile and efficient synthetic method for 3-aminoquinolines has been reported. The straightforward process starts from easily available triazoles and 2-aminobenzaldehydes. Low catalyst loading and good functional group compatibility are the other two merits of this transformation. Easy decoration of the 3-aminoquinoline motifs enabled the convenient synthesis of bioactive molecules, demonstrating the potential of this protocol in organic synthesis.

Access to tetrahydrocarbazoles and pyrrolo[3,4-b]carbazoles through sequential reactions of triazoles and indoles.

Tetrahydrocarbazoles and pyrrolo[3,4-b]carbazoles could be synthesized conveniently through sequential reactions of ester-tethered 1-sulfonyl-1,2,3-triazoles and indoles. The reaction conditions were mild and the procedures were quite simple. Moreover, the key intermediate α,ß-unsaturated imine acted as a [2C] synthon in the [4 + 2] cycloaddition reaction, and the imino group could be used as a nucleophile to construct the fourth ring.

Synthesis of benzothiazonine by rhodium-catalyzed denitrogenative transannulation of 1-sulfonyl-1,2,3-triazole and thiochromone.

A facile synthesis of multi-functionalized benzothiazonine was achieved by the rhodium-catalyzed denitrogenative annulation of 1-sulfonyl-1,2,3-triazole and thiochromone. In view of the excellent atom economy, broad substrate scope and easy availability of starting materials, the protocol provided an efficient strategy for the construction of medium N,S-heterocycles.

From Oxygen to Sulfur and Back: Difluoro -H-phosphinothioates as a Turning Point in the Preparation of Difluorinated Phosphinates: Application to the Synthesis of Modified Dinucleotides.

A simple, two-step procedure to convert α,α-difluorinated H-phosphinic acids into the corresponding H-phosphinothioates is described. The usefulness of these species is demonstrated by their transformation into difluorinated phosphinothioyl radicals and their addition onto alkenes. Additionally, sequential treatment of H-phosphinothioates by a strong base and a primary alkyl iodide constitutes an alternate route to the formation of the C-P bond. Both methods efficiently deliver difluorinated phosphinothioates. Similar reactions carried out with the fully oxygenated counterparts clearly indicate the superiority of the sulfur-based species and emphasize the crucial role played by sulfur in the construction of the second C-P bond. Oxidation easily transforms the thereby obtained phosphinothioates into the corresponding phosphinates. The whole strategy is applied to the stereoselective preparation of dinucleotide analogues featuring either a difluorophosphinothioyl or a difluorophosphinyl unit linking the two furanosyl rings.

Metal-free synthesis of imidazole by BF3·Et2O promoted denitrogenative transannulation of N-sulfonyl-1,2,3-triazole.

BF3·Et2O promoted metal-free denitrogenative transannulation of N-sulfonyl-1,2,3-triazole was reported. Rather than transition metals, BF3·Et2O was employed for the first time to promote the formation of α-diazoimines from N-sulfonyl-1,2,3-triazoles in nitriles, leading to the synthesis of various imidazoles. The protocol tolerates a broad range of functional groups and could also be applied to the late-stage modification of bioactive molecules, demonstrating the potential of this protocol in organic synthesis. A plausible mechanism was proposed.

Metal-free synthesis of 2-aminonaphthalenes by intramolecular transannulation of 1-sulfonyl-4-(2-alkenylphenyl)-1,2,3-triazoles.

A facile metal-free synthesis of naphthalenes by intramolecular transannulation of 1-sulfonyl-4-(2-alkenylphenyl)-1,2,3-triazoles was realized. The in situ formed ketenimine was proposed as the key intermediate, and the desired 2-aminonaphthalenes were generated in up to 87% yield in refluxing 1,2-dichloroethane without any catalyst or additive.

Copper-Catalyzed Synthesis of Furan-Tethered Benzocyclobutenes via Carbene-Mediated 1,4-Sulfinate Migration-Annulation.

A copper-catalyzed intramolecular cascade reaction of conjugated enynones has been achieved via a pivotal 1,4-sulfinate migration step. This process leverages a cost-effective and ecofriendly copper salt as catalyst, enabling the efficient construction of five- and four-membered rings in a rapid, sequential manner, producing furan-tethered benzocyclobutenes in good to excellent yields under mild conditions. The reaction is characterized by 100% atom economy, outstanding efficiency, and excellent diastereoselectivity in the cases studied. The robustness of this method is evidenced by its compatibility with air exposure and the use of undistilled, commercially available solvents, further enhancing its practicality.

Fe-TiO2-x/TiO2 S-scheme homojunction for efficient photocatalytic CO2 reduction.

CO2-to-high value-added chemicals via a photocatalytic route is of interest but strangled by the low efficiency. Herein, a novel Fe-TiO2-x/TiO2 S-scheme homojunction was designed and constructed by using a facile surface modification approach whereby oxygen vacancy (OV) and Fe introducing on the TiO2 nanorod surface. The as-synthesized Fe-TiO2-x/TiO2 S-scheme homojunction exhibits positive properties on promoting photocatalytic CO2 reduction: i) the nanorod structure provides numerous active sites and a radical charge transfer path; ii) the doped Fe and OV not only synergistically enhance light utilization but also promote CO2 adsorption; iii) the Fe-TiO2-x/TiO2 S-scheme homojunction benefits photoexcited charge separation and retains stronger redox capacity. Thanks to those good characters, the Fe-TiO2-x/TiO2 homojunction exhibits superior CO2 reduction performances with optimized CO/CH4 generation rates of 122/22 µmol g-1h-1 which exceed those of pure TiO2 by more than 9.4/7.3 folds and most currently reported catalytic systems. This manuscript develops a facile and universal approach to synthesize well-defined homojunction and may inspire the construction of other more high-efficiency photocatalysts toward CO2 reduction and beyond.

Synthesis of Piperidin-4-one Derivatives via α-Imino Rhodium Carbene-Initiated 1,2-Aryl/Alkyl Migration and Annulation.

Valuable piperidin-4-one derivatives were synthesized in excellent yields via an α-imino carbene-initiated cascade reaction involving 1,2-aryl/alkyl migration and annulation. The excellent selectivity of alkyl migration was attributed to the neighboring group participation of 2-bromoethyl. Features such as high efficiency, excellent migrating selectivity, broad substrate scope, and convenient one-pot procedure qualified this protocol as an effective tool for piperidine derivative synthesis. The product could be transformed to a bioactive molecule easily. The migration-annulation reaction of α-imino carbene provided a powerful strategy for heterocycle construction.

Synthesis of Azepane Derivatives via Formal 1,3-Migration of Hydroxy and Acyloxy Groups and Selective Annulation.

Formal 1,3-migration of hydroxy and acyloxy groups initiated by α-imino rhodium carbene was achieved, and the following selective annulations of the corresponding zwitterions could efficiently afford azepane derivatives. Benefiting from a time-saving procedure as well as a good functional group tolerance, this unique migration-annulation protocol could provide an efficient tool for synthesizing seven-membered N-heterocycles. The plausible mechanism is discussed.

Synthesis of dihydropyrroles from in situ-generated zwitterions via Rh2(adc)4/TBAI dual catalysis.

Triggered by formation of α-imino carbene, the regioselective synthesis of dihydropyrroles was achieved via a cascade 1,3-sulfinate migration/annulation. The sulfinate group was converted into sulfone during the group migration, and a stable anion bearing two electron-withdrawing groups was thus formed. The addition of a catalytic amount of iodide is believed to assist the cleavage of the C-O bond, and the formation of a more stable carbocation. Thermodynamic product dihydropyrroles were produced efficiently rather than kinetic product cyclopropanes. This dual catalysis system would afford chemists a new strategy to control the annulation selectivity of zwitterions bearing multiple reactive sites and may be employed in flexible and divergent synthesis of different ring systems.

Synthesis of α-Amino Cyclobutanones via Formal 1,3-Hydroxy Migration Triggered by Formation of α-Imino Rhodium Carbene.

Formal intramolecular 1,3-OH migration of α-imino carbene was achieved producing a unique zwitterion, and the subsequent selective annulation afforded α-amino cyclobutanone. Features such as readily available substrates, mild reaction conditions, a time-saving procedure, excellent functional group compatibility, and valuable transformations of the products qualified this unique protocol as an efficient tool for the synthesis of strained cyclic compounds. Density functional theory calculations were in good agreement with experimental observations, and a plausible mechanism is presented.

Synthesis of Cyclopropanes via 1,3-Migration of Acyloxy Groups Triggered by Formation of α-Imino Rhodium Carbenes.

A novel and highly efficient synthetic approach to cyclopropanes was realized via 1,3-migration of acyloxy groups triggered by α-imino rhodium carbenes. Excellent chemoselectivity ensured broad compatibility of common functional groups. Merits such as readily available substrates, mild reaction conditions, and time-saving processes qualified this transformation as an attractive alternative strategy to synthesize multifunctionalized cyclopropanes. Primary investigations and discussion on the mechanism are presented.

[Polymorphisms of RAD51(G135C) and XRCC3(C241T) genes and correlations thereof with prognosis and clinical outcomes of acute myeloid leukemia].

OBJECTIVE: To investigate the impacts of RAD51G(135C) and XRCC3(C241T) genotypes on the response, adverse effects, and prognosis of acute myelocytic leukemia (AML). METHODS: RAD51(G135C), XRCC3(C241T), GSTT1, and GSTM1 genotypes were analyzed in 372 patients with AML, 226 males and 146 females, by PCR-RFLP or PCR. The Complete remission (CR) rate, adverse effects, overall survival (OS), and relapse-free survival (RFS) were compared among the groups with different genotypes. RESULTS: (1) During the induction chemotherapy, XRCC3(C241T) polymorphic allele was significantly associated with the shorter survival of the AML patients with t (15; 17)/PML-RARalpha (OR = 8.750, P = 0.046). Among the non-M3 patients, the complete remission (CR) rate of those with double RAD51(G135C) and GSTT1 wild genotypes was 71.6%, significantly higher than that of those not with double RAD51(G135C) and GSTT1 wild genotypes (54.4%, P = 0.028). (2) The OS of the non-M3 AML patients with double RAD51(G135C) and GSTT1 wild genotypes was (39.1 +/- 7.1) months, significantly longer than those with double variant types [(22.4 +/- 3.2) months, P = 0.042]. The relapse-free survival (RFS) of the M4EO and M2 patients with double XRCC3(C241T) and GSTT1 wild type genotype were 48.3 months and 56.5 months, both significantly longer than those of the patients with double variant genotypes (28.8 months and 10.0 months respectively, both P < 0.05). The OS of the M2 patients with triple RAD51(G135C), GSTT1, and GSTM1 variant genotypes was (22.4 +/- 3.2) months, significantly shorter than those with triple RAD51(G135C), GSTT1, and GSTM1 wild genotypes [(39.1 +/- 7.1) months, P = 0.042]. The RFS of the M2 patients with triple RAD51(G135C), GSTT1, and GSTM1 variant genotypes was 10.0 months, significantly shorter than that of the patients with triple RAD51(G135C), GSTT1, and GSTM1 wild genotypes (64.2 months, P = 0.015). (3) The risk levels of neutropenia, nausea and vomiting, and alopecia of the patients with variant XRCC3(C241T) genotype were all significantly higher than those of the wild type genotype (all P < 0.05). The risk of hematuria of the patients with variant genotype was significantly higher than that of the patients with wild genotype (P = 0.017). CONCLUSION: The polymorphisms of XRCC3(C241T) and RAD51(G135C) genes are significantly related to response to therapy, adverse effects, and prognosis of AML. Detection of the XRCC3(C241T) and RAD51(G135C) genotypes may be useful in selecting individual chemotherapy regimens for patients with AML.

Metal-Free Synthesis of (E)-Monofluoroenamine from 1-Sulfonyl-1,2,3-triazole and Et2O·BF3 via Stereospecific Fluorination of α-Diazoimine.

A general, stereospecific, and straightforward method for the rapid preparation of functionalized (E)-monofluoroenamines is reported. Rather than transition metals (Rh, Ni, Pd, Cu, Ag, etc.), Et2O·BF3 was employed to promote the formation of α-diazoimine through the Dimroth equilibrium of common 1-sulfonyl-1,2,3-triazole for the first time. An overall migration of fluoride from boron to the diazo-linked carbon of α-diazoimine was achieved. Derivations and late-stage modification of bioactive molecule were conducted. A plausible mechanism was also proposed.

[Analysis of Early-Death and Factors Affecting Prognosis of Patients with Acute Promyelocytic Leukemia].

OBJECTIVE: To investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients. METHODS: The clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed. RESULTS: Among total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 109/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048). CONCLUSION: Importance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 109/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.

Rhodium-catalyzed synthesis of 1,2-dihydropyridine by a tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole.

A tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole including formation of α-imino rhodium carbene, 1,2-migration of an acetoxy group and six electron electrocyclic ring closure was reported. The migration of the OAc group with excellent chemoselectivity was the crucial process, leading to the formation of 1,2-dihydropyridine specifically in up to 90% yield. Several transformations of the dihydropyridine product were also achieved illustrating the potential of the protocol in organic synthesis. Based on the observation of the intermediate, a plausible mechanism was proposed.

Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by relative quantification with real-time polymerase chain reaction.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region and has a poor prognosis. Cytokeratin 19 (CK19) is a component of cytoskeleton protein. Previous studies have reported abnormal expression of CK19 protein in OSCC tissue. This study is to investigate the quantitative level of CK19 gene transcript in OSCC tissue as well as its clinical significance. Thirty-one OSCC patients (26 males and 5 females) took part in the present study, aged 34-78 years (mean 58.2 years). The level of CK19 mRNA was detected using fluorescent quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) in cancerous and paracancerous tissues. The relative quantification in cancerous tissue compared with paracancerous tissue was calculated using the 2(-DeltaDeltaCt) equation. The level of CK19 mRNA in cancerous tissue from OSCC patients was 2.21-fold higher than that in paracancerous tissue (P=0.020), and the amplicon was specific without genomic DNA contamination. The level of CK19 mRNA correlated significantly with the pathological differentiation grade of OSCC tissue (P=0.025), with poorer differentiation indicating a higher level of CK19 mRNA. These results suggest that fluorescent quantitative real-time RT-PCR is accurate and reliable for the detection of CK19 gene transcript levels in OSCC tissue. The level of CK19 mRNA was increased in OSCC tissue, and this was significantly correlated with the pathological differentiation grade.

[Knockdown of PLK1 mRNA by special siRNA].

To study knockdown effect of small interfering RNA (siRNA) to PLK1 (Polo-like kinase 1) mRNA in colorectal cancer cell line SW480 and its mitosis and growth was changed. Ten special siRNA molecules were designed targeting different sites of PLK1 mRNA sequence and chemically synthesized. The siRNA molecules were transfected into SW480 by Oligofectamine. The gene mRNA level was assayed by Real-Time PCR. The changes of PLK1 protein, SW480 cell cycle and survival percentage was checked by Western-blot, Flow cytometry and Cell counter assays respectively. All 10 siRNA molecules knocked PLK1 mRNA down in different level. Of them P1, P4 and P9 showed over 80% knockdown efficiency and the others had more than 20% knockdown efficiency to PLK1 mRNA. The best knockdown effect over 95% of all groups was at 25 nmol/L of a mixture with P1, P4 and P9 siRNA equally. In this situation the protein was very less and the cells were blocked at G2 phase of cell cycle. After 72 h cell survival percentages were consistent with PKL1 mRNA level change by siRNA gradient concentration. The results showed that siRNA targeting PLK1 mRNA had effectively knocked PLK1 mRNA down in SW480 cell line. And a blended siRNAs held the best knockdown effect. The cell was blocked on the mitosis and growth.