Cp*Rh(III)-Catalyzed Regioselective C(sp2)-H Mono- and Dialkynylation of Thioamides by Sulfur Coordination.

An efficient Cp*Rh(III)-catalyzed regioselective C(sp2)-H mono- and dialkynylation of thioamides was described. This reaction was performed under mild conditions in high yields (up to 98%) with a broad substrate scope. Significantly, the versatility of this method was further demonstrated by controlled mono- and dialkynylation. Application of this protocol in the late stage functionalization of two drug molecules (Adapalene and Amoxapine) was also demonstrated.

Metal-free sulfonylation of arenes with N-fluorobenzenesulfonimide via cleavage of S-N bonds: expeditious synthesis of diarylsulfones.

A novel metal-free sulfonylation of arenes with N-fluorobenzenesulfonimide (NFSI) toward the synthesis of diarylsulfones has been developed. The reaction represents a rare example of sulfonylation reaction using NFSI as an efficient sulfonyl donor and the first example of acid-mediated sulfonylation of unactivated arenes with NFSI via selective cleavage of S-N bonds. This protocol provides a concise approach for the construction of pharmaceutically and biologically important diarylsulfones. Applications in the functionalization of natural products (e.g., ß-estradiol) and in the synthesis of a key intermediate to an inhibitor of farnesyl-protein transferase, as well as in the gram-scale synthesis of the EPAC2 antagonist, are demonstrated.

Cobalt(III)-catalyzed C-H amidation of N,N-dialkyl thiobenzamides by sulfur coordination.

An efficient inexpensive cobalt(III)-catalyzed intermolecular amidation of N,N-dialkyl thiobenzamides with 1,4,2-dioxazol-5-ones via C-H bond activation is described. The reaction proceeds with high functional group tolerance under external oxidant free conditions, providing a straightforward approach for the direct modification of thioamide derivatives, which are prevalent organic motifs found in vital biological and pharmaceutical molecules.

[Prognostic Value of 18F-FDG PET/CT Metabolic Parameters in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the prognostic value of metabolic parameters of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 58 patients with DLBCL who were examined by 18F-FDG PET/CT before treatment and confirmed by pathology were analyzed retrospectively. The relationships between maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and clinical factors were analyzed. Kaplan Meier method, Log-rank test and multivariate Cox regression were used to analyze the relationships between metabolic SUVmax, MTV, TLG and times of total overall survival (OS) and progression-free survival (PFS). RESULTS: The SUVmax, MTV and TLG of 58 DLBCL patients were 21.45 (10.26-42.38), 27.30 (14.20-133.25) cm3 and 322.85 (47.35-1438.20), respectively. Univariate analysis showed that large mass, Ann Arbor stage, international prognostic index, MTV and TLG were the factors influencing OS and PFS in DLBCL patients (P<0.05), while lactate dehydrogenase and SUVmax were the factors influencing PFS only (P<0.05). Multivariate analysis showed that MTV (HR=2.974, 95%CI: 1.803-7.225)/(HR=3.925, 95%CI: 1.973-8.246) and TLG (HR=2.583, 95%CI: 1.192-5.316)/(HR=2.874, 95%CI: 1.538-6.483) were independent risk factors for OS and PFS in DLBCL patients (P<0.05), and international prognostic index (HR=2.490, 95%CI: 1.150-4.962) was independent risk factor for OS in DLBCL patients (P<0.05). CONCLUSION: MTV and TLG are independent risk factors for OS and PFS in patients with DLBCL, which may be valuable for prognosis of patients with DLBCL.

[Differential Diagnostic Value of 18F-FDG PET/CT Imaging in Multiple Myeloma and Bone Metastases].

OBJECTIVE: To investigate the imaging characteristics of 18F-FDG positron emission computed tomography (18F-FDG PET/CT) in multiple myeloma (MM) patients and to analyze its application value in MM and bone metastases. METHODS: A retrospective analysis was made on MM patients (n=72) and bone metastases patients (n=50) admitted to Hainan Western Central Hospital from January 2017 to March 2019. All patients underwent 18F-FDG PET/CT examination. The distribution of lesions, bone destruction, maximum standardized uptake (SUVmax) and metabolic homogeneity were analyzed in both groups. RESULTS: More than 80% of MM and bone metastases involved thoracic bone, spine and pelvis, followed by limbs. MM was more common in the lesions of thoracic bone and skull than those in bone metastases, the difference was statistically significant (P＜0.05). The majority of MM patients presented osteolytic bone destruction (97.2%), mostly showing "insect-like phagocytic pattern", so the bone showed dilated changes, and osteogenic changes were rarely seen (2.8%). Osteolytic bone destruction accounted for 74.0% in patients with bone metastatic tumor, presenting "focal" appearance more often, and osteogenic changes accounted for 26.0%. Osteolytic bone destruction in patients with MM was significantly higher than that in patients with bone metastases（χ2=14.757，P＜0.05）. The SUVmax of MM (4.25±2.16)was significantly lower than that of bone metastases (7.84±3.25) (t=6.830, P＜0.05). Diffuse mild uptake of 18F-FDG was more common in patients with MM, and heterogeneous high uptake of 18F-FDG was more common in patients with bone metastasis, the difference was statistically significant (P＜0.05). CONCLUSION: 18F-FDG PET/CT examination is helpful to acquire the imaging features of bone structure and metabolic changes, and shows an important clinical value in the differential diagnosis of MM and bone metastases.

Copper-catalyzed intermolecular amidation of 8-methylquinolines with N-fluoroarylsulfonimides via Csp(3)-H activation.

An efficient copper-catalyzed C-H amidation of 8-methylquinolines with N-fluoroarylsulfonimides via Csp(3)-H activation is described. The reaction proceeds with high functional group tolerance, providing a novel approach to valuable quinolin-8-ylmethanamine derivatives in the absence of an additional oxidant.

Ag-catalyzed C-H/C-C bond functionalization.

Silver, known and utilized since ancient times, is a coinage metal, which has been widely used for various organic transformations in the past few decades. Currently, the silver-catalyzed reaction is one of the frontier areas in organic chemistry, and the progress of research in this field is very rapid. Compared with other transition metals, silver has long been believed to have low catalytic efficiency, and most commonly, it is used as either a cocatalyst or a Lewis acid. Interestingly, the discovery of Ag-catalysis has been significantly improved in recent years. Especially, Ag(i) has been demonstrated as an important and versatile catalyst for a variety of organic transformations. However, so far, there has been no systematic review on Ag-catalyzed C-H/C-C bond functionalization. In this review, we will focus on the development of Ag-catalyzed C-H/C-C bond functionalization and the corresponding mechanism.

NBS mediated nitriles synthesis through C=C double bond cleavage.

An NBS mediated nitriles synthesis through C=C double bond cleavage has been developed. TMSN3 was employed as the nitrogen source for this Cu(OAc)2 promoted nitrogenation reaction. This transformation has a relatively high regio-selectivity to form aromatic nitriles.

Pd-catalyzed tandem C-H azidation and N-N bond formation of arylpyridines: a direct approach to pyrido[1,2-b]indazoles.

A novel Pd-catalyzed nitrogenation of arylpyridines via C-H azidation has been developed. Direct C-N and N-N formations are achieved for this N-atom incorporation transformation using azides as the N-atom source. This method provides an alternatively concise approach for the construction of bioactively important pyrido[1,2-b]indazoles.

Ru(II)-catalyzed intermolecular C-H amidation of weakly coordinating ketones.

An efficient Ru(II)-catalyzed intermolecular amidation of weakly coordinating ketones with sulfonyl azides via C-H bond activation is described. The reaction proceeds with high functional group tolerance, providing a novel approach to practical ketone-directed intermolecular C-N bond formation in the absence of an additional oxidant.

[Clinical application of self-regulating exterior bracket for zygomatic fracture].

PURPOSE: To investigate the clinical value of self-regulating exterior bracket for zygomatic fracture. METHODS: Thirty patients with unilateral zygomatic fracture were treated using self-regulating exterior bracket. They all had limitation of mouth opening and facial collapse. 1.5 cm incision was made from the distal upper first molar. After reducting to normal mouth opening and symmetrical face, self-regulating external bracket was used to fix the fracture for 3 weeks. RESULTS: After removing the self-regulating bracket, X-ray showed the fracture healing well. The patients had normal mouth opening. CONCLUSION: The clinical effect of using self-regulating bracket to fix fracture after reduction for unilateral zygomatic fracture is good, it is a simple surgical method.

Synthesis, biological evaluation, and molecular docking studies of 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety as potential antitumor agents.

A series of new 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety were synthesized. Antiproliferative assay results indicated that compounds 6o and 6u exhibited the most potent activity against gastric cancer cell SGC-7901, which was more potent than the positive control. Especially, compound 6o exhibited significant telomerase inhibitory activity (IC(50)=2.3±0.07µM), which was comparable to the positive control ethidium bromide. Docking simulation was performed to position compound 6o into the active site of telomerase (3DU6) to determine the probable binding model.

[Clinical study of two fixed prosthetics in dentition defect of Kennedy I and II type].

PURPOSE: To investigate the feasibility and clinical effect of two fixed prosthetic, supported by implant alone or by implant and natural teeth, in dentition defect of Kennedy I or II type. METHODS: Sixty subjects with dentition defect of Kennedy I or II were collected. They were divided into group A and group B, 30 subjects in each group respectively. Group A was restore with PFM crown or bridge, supported by implant or implant combined with natural teeth. Group B was treated by cantilever fixed bridge supported by natural teeth. The treatment outcomes were analyzed with SPSS17.0 software package. RESULTS: With 5 years of follow-up, all subjects in group A and 26/30 subjects in group B had successful restoration. There was significant difference in successful rate between group A and group B(P<0.05). CONCLUSION: Fixed prosthetics supported by implant alone and by both implant and natural teeth, in dentition defect of Kennedy I or II is feasible and its clinical effect is satisfactory. Supported by Research Fund of Science and Technology Commission of Fengxian District, Shanghai Municipality(Grant No.96-3).

Synthesis, molecular modeling and biological evaluation of dithiocarbamates as novel antitubulin agents.

A series of novel dithiocarbamate compounds with the chalcone scaffold have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and antitubulin polymerization inhibitors. Compound 2n showed the most potent biological activity in vitro, which inhibited the growth of MCF-7 cells with IC(50) of 0.04+/-0.01 microM and the polymerization of tubulin with IC(50) of 6.8+/-0.6 microM. To understand the tubulin-inhibitor interaction and the selectivity of the most active compound towards tubulin, molecular modeling studies were performed to dock compound 2n into the colchicine binding site, which suggested probable inhibition mechanism.

Synthesis of theanine from glutamic acid gamma-methyl ester and ethylamine catalyzed by Escherichia coli having gamma-glutamyltranspeptidase activity.

Glutamic acid gamma-methyl ester (GAME) was used as substrate for theanine synthesis catalyzed by Escherichia coli cells possessing gamma-glutamyltranspeptidase activity. The yield was about 1.2-fold higher than with glutamine as substrate. The reaction was optimal at pH 10 and 45 degrees C, and the optimal substrate ratio of GAME to ethylamine was 1:10 (mol/mol). With GAME at 100 mmol, 95 mmol theanine was obtained after 8 h.

Synthesis of some N-alkyl substituted urea derivatives as antibacterial and antifungal agents.

A series of N-alkyl substituted urea derivatives were synthesized and evaluated for their in vitro antibacterial and antifungal activities. The N-alkyl substituted urea derivatives bearing morpholine moiety (3a-3k) showed better activities than those bearing diethylamine moiety (2a-2f). Compounds having fluoro substituent at ortho (3c) and para (3b) positions of the phenyl ring exhibited potent antimicrobial activities against Gram-positive and Gram-negative bacteria as well as fungi.

Synthesis, molecular modeling and biological evaluation of PSB as targeted antibiotics.

We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli beta-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure-activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4-methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20-3.13microg/mL and 0.39-3.13microg/mL against various bacteria.

Enzymatic synthesis of theanine from glutamic acid γ-methyl ester and ethylamine by immobilized Escherichia coli cells with γ-glutamyltranspeptidase activity.

Theanine (γ-glutamylethylamide) is the main amino acid component in green tea. The demand for theanine in the food and pharmaceutical industries continues to increase because of its special flavour and multiple physiological effects. In this research, an improved method for enzymatic theanine synthesis is reported. An economical substrate, glutamic acid γ-methyl ester, was used in the synthesis catalyzed by immobilized Escherichia coli cells with γ-glutamyltranspeptidase (GGT) activity. The results show that GGT activity with glutamic acid γ-methyl ester as substrate was about 1.2-folds higher than that with glutamine as substrate. Reaction conditions were optimized by using 300 mmol/l glutamic acid γ-methyl ester, 3,000 mmol/l ethylamine, and 0.1 g/ml of immobilized GGT cells at pH 10 and 50°C. Under these conditions, the immobilized cells were continuously used ten times, yielding an average glutamic acid γ-methyl ester to theanine conversion rate of 69.3%. Bead activity did not change significantly the first six times they were used, and the average conversion rate during the first six instances was 87.2%. The immobilized cells exhibited favourable operational stability.

Synthesis, biological evaluation and molecular docking studies of amide-coupled benzoic nitrogen mustard derivatives as potential antitumor agents.

A series of amide-coupled benzoic nitrogen mustard derivatives as potential EGFR and HER-2 kinase inhibitors were synthesized and reported for the first time. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Of all the studied compounds, compounds 5b and 5t exhibited the most potent inhibitory activity, which was comparable to the positive control erlotinib. Docking simulation was performed to position compounds 5b and 5t into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicated that some of the benzoic nitrogen mustard derivatives possessed high antiproliferative activity against MCF-7. In particular, compounds 5b and 5t with potent inhibitory activity in tumor growth inhibition may function as potential antitumor agents.