Synthesis of Carboranylated Dihydropyrrolo[1,2-a]quinoxalines and Dihydroindolo[1,2-a]quinoxalines by BF3·OEt2-Catalyzed Heterocyclization of C-Formyl-o-carboranes and Investigation of Their Oxidation Stability.

A BF3·OEt2-catalyzed synthesis of carboranylated dihydropyrrolo[1,2-a]quinoxalines and dihydroindolo[1,2-a]quinoxalines in 30-99% yields is presented through the heterocyclization of various C-modified C-formyl-o-carboranes with 1-(2-aminophenyl)-pyrroles/indoles. A systematic comparative investigation of their oxidation stability in air confirmed that 4-carboranyl-4,5-dihydropyrrolo[1,2-a]quinoxaline had better stability than the 4-phenyl analogue. A cage-deboronation reaction for N-acetyl-substituted carboranylated dihydropyrrolo[1,2-a]quinoxaline produced the corresponding 7,8-nido-carborane cesium salt. A kinetic resolution was also realized to obtain an optically pure carboranylated N-heterocycle scaffold bearing a carborane cage carbon-bonded chiral stereocenter.

Enantioselective Synthesis of Biphenyl-Bridged ϵ-Sultams by Organocatalytic Mannich Reactions of Cyclic N-Sulfonylimines with Unactivated Ketones.

A highly enantioselective Mannich reaction of biphenyl-bridged seven-membered cyclic N-sulfonylimines with methyl alkyl ketones is disclosed in this study. The reaction was performed under organocatalysis by using a quinine-derived primary amine as the catalyst in combination with a Brønsted acid as the co-catalyst. High yields (up to 89 %) and excellent enantioselectivities (up to 97 % ee) were observed. For methyl alkyl ketones containing a larger alkyl substituent, specific regioselective addition to the C=N bond is favored at the methyl group. On the contrary, ketones containing a smaller alkyl substituent or hydroxyacetone substrates gave major syn selective Mannich products at the methylene group.

Catalytic asymmetric synthesis of carboranylated diols bearing two adjacent stereocenters located at the α,ß-position of o-carborane cage carbon.

Despite the great interest in carborane-containing molecules, there is a lack of literature on the generation of central chiralities, via catalytic asymmetric transformations using prochiral carboranyl substrates. Herein, we have synthesized novel optically active icosahedral carborane-containing diols via Sharpless catalytic asymmetric dihydroxylation of carborane-derived alkenes, under mild conditions. The reaction showed a good substrate scope with 74-94% yields and 92->99% ee. This synthetic approach facilitated the creation of two adjacent stereocenters respectively located at the α,ß-position of o-carborane cage carbon, with a single syn-diastereoisomer. In addition, the obtained chiral carborane-containing diol product can be transformed to cyclic sulfate and can subsequently undergo a nucleophilic substitution and reduction to obtain the unexpected nido-carboranyl derivatives of chiral amino alcohols in the form of zwitterions.

Chiral Chalcogenide-Catalyzed Enantioselective Electrophilic Hydrothiolation of Alkenes.

A new strategy for the construction of chiral sulfides by catalytic enantioselective hydrothiolation of alkenes via an electrophilic pathway has been developed. Using this strategy, cyclic and acyclic unactivated alkenes efficiently afforded various chiral products in the presence of electrophilic sulfur reagents and silanes through chiral chalcogenide catalysis. The obtained products were easily transformed into other types of valuable chiral sulfur-containing compounds. Mechanistic studies revealed that the superior construction of chiral thiiranium ion intermediate is the key to achieving such a transformation.

Cancer incidence and mortality in Zhejiang Province, Southeast China, 2016: a population-based study.

BACKGROUNDS: Cancer is one of the main causes of death worldwide, seriously threatening human health and life expectancy. We aimed to analyze the cancer incidence and mortality rates during 2016 in Zhejiang Province, Southeast China. METHODS: Data were collected from 14 population-based cancer registries across Zhejiang Province of China. Cancer incidence and mortality rates stratified by sex and region were analyzed. The crude rate, age-standardized rate, age-specific and region-specific rate, and cumulative rate were calculated. The proportions of 10 common cancers in different groups and the incidence and mortality rates of the top five cancers in different age groups were also calculated. The Chinese national census of 2000 and the world Segi population was used for calculating the age-standardized incidence and mortality rates. RESULTS: The 14 cancer registries covered a population of 14,250,844 individuals, accounting for 29.13% of the population of Zhejiang Province. The total reported cancer cases and deaths were 55,835 and 27,013, respectively. The proportion of morphological verification (MV%) was 78.95% of the population, and percentage of incident cases identified through death certificates only (DCO%) was 1.23% with a mortality-to-incidence ratio (M/I ratio) of 0.48. The crude incidence rate in Zhejiang cancer registration areas was 391.80/105; the age-standardized incidence rate of the Chinese standard population (ASIRC) and the age-standardized incidence rate of the world standard population (ASIRW) were 229.76/105 and 220.96/105, respectively. The incidence rate in men was higher than that in women. The incidence rate increased rapidly after 45 years of age and peaked in individuals aged 80 to 84 years. The top 10 incidence rates of cancers were lung cancer, female breast cancer, thyroid cancer, colorectal cancer, stomach cancer, liver cancer, prostate cancer, cervical cancer, esophageal cancer, and pancreatic cancer (from highest to lowest). The crude mortality rate in Zhejiang cancer registration areas was 189.55/105; the age-standardized mortality rate of the Chinese standard population (ASMRC) and the age-standardized mortality rate of the world standard population (ASMRW) were 94.46/105 and 93.42/105, respectively. The mortality rate in men was higher than that in women, and the male population in rural areas was higher than that in urban areas. The cancer mortality rate increased rapidly after 50 years of age and peaked in individuals aged 85+ years. The top 10 mortality rates of cancers were lung cancer, liver cancer, stomach cancer, colorectal cancer, pancreatic cancer, esophageal cancer, female breast cancer, prostate cancer, lymphoma, and leukemia (from highest to lowest). CONCLUSIONS: Lung cancer, female breast cancer, thyroid cancer, colorectal cancer, prostate cancer, liver cancer, and stomach cancer were the most common cancers in Zhejiang Province. Effective prevention and control measures should be established after considering the different characteristics of cancers in urban and rural areas.

Dissymmetric interface design of SnO2/TiO2 side-by-side bi-component nanofibers as photoanodes for dye sensitized solar cells: Facilitated electron transport and enhanced carrier separation.

SnO2/TiO2 type II heterojunctions are often introduced to enhance the separation efficiency of photogenerated carriers in photoelectrochemical electrodes, while most of these heterojunctions are of core-shell structure, which often limits the synergistic effect from the two components. In this work, dissymmetric SnO2/TiO2 side-by-side bi-component nanofibers (SBNFs) with tunable composition ratios have been prepared by a novel needleless electrospinning technique with two V-shape connected conductive channels (V-channel electrospinning). Results show that this V-channel electrospinning technique is more stable, controllable and tunable for the large-scale preparation of SBNF materials compared to the traditional electrospinning using two side-by-side metal needles. And these SnO2/TiO2 SBNFs are dissymmetric and comprised of a tiny SnO2 NF (tunable diameter within 20-80 nm) and a Sn-doped TiO2 NF (diameter of ~ 250 nm) with a side-by-side structure. Moreover, the dye-sensitized solar cells (DSSCs) based these dissymmetric SnO2/TiO2 SBNFs show the maximum power conversion efficiency (PCE) of 8.3%, which is 2.59 times that of the ones based on the TiO2 NFs. Series of analyses indicate that the enhancements in PCE could mainly be due to the improved electron transport via SnO2 NFs and the enhanced carrier separation via dissymmetric SnO2/TiO2 heterojunction interface. This research will give some new insight in the preparation of SBNFs for high-performance photoelectrochemical devices.

C2-Symmetric 1,2-Diphenylethane-1,2-diamine-Derived Primary-Tertiary Diamine-Catalyzed Asymmetric Mannich Addition of Cyclic N-Sulfonyl Trifluoromethylated Ketimines.

A simple chiral primary-tertiary diamine derived from C2-symmetric 1,2-diphenylethane-1,2-diamine as the organocatalyst in combination with the trifluoroacetic acid additive for the asymmetric Mannich reaction of cyclic N-sulfonyl trifluoromethylated ketimines and methyl ketones afforded the desired product with high enantioselectivity (73-96% ee). The reactions proceeded well for a variety of different substituted cyclic N-sulfonyl trifluoromethyl ketimines and various alkyl methyl ketones, providing access to diverse enantioenriched benzo-fused cyclic sulfamidate N-heterocycles bearing a trifluoromethylated α-tetrasubstituted carbon stereocenter. This study also investigated the diastereoselective reduction of the carbonyl group and ring cleavage reduction of the sulfamidate group of the corresponding Mannich product.

Enantioselective (3+2) cycloaddition via N-heterocyclic carbene-catalyzed addition of homoenolates to cyclic N-sulfonyl trifluoromethylated ketimines: synthesis of fused N-heterocycle γ-lactams.

An enantioselective (3+2) cycloaddition of enals and cyclic N-sulfonyl trifluoromethyl ketimines via N-heterocyclic carbene-catalyzed homoenolate addition is described. This reaction can efficiently construct fused N-heterocycle γ-lactams bearing two adjacent chiral centers with >20 : 1 dr and 94-99% ee, with one chiral center as a trifluoromethylated α-tetrasubstituted carbon stereocenter.

Enantioselective organocatalytic Michael additions of N,N'-dialkylbarbituric acids to enones.

N,N'-Dialkylbarbituric acids as cyclic malonamide donors were successfully used in the enantioselective Michael addition reaction of enones. Using cinchona alkaloid-based bifunctional squaramide as an organocatalyst, this Michael reaction of N,N'-di-tert-butylbarbituric acid with various enones features a highly enantioselective (91-99% ee) production of the corresponding optically active 5-substituted barbituric acid derivatives. The transformations of the Michael product for the barbituric acid structural unit were realized in two ways, deprotection to remove the N-tert-butyl group and alkylation to produce 5,5-disubstituted barbituric acid derivatives.

Asymmetric Mannich Reaction of Aryl Methyl Ketones with Cyclic Imines Benzo[e][1,2,3]oxathiazine 2,2-Dioxides Catalyzed by Cinchona Alkaloid-based Primary Amines.

Aryl ketones represent problematic substrates for asymmetric Mannich reactions due to a large steric hindrance exhibited by such compound species. A highly enantioselective direct Mannich reaction of aryl methyl ketones with cyclic imine benzo[e][1,2,3]oxathiazine 2,2-dioxides could be successfully carried out utilizing a combination of cinchona alkaloid-derived primary amines with trifluoroacetic acid (TFA); the primary amines feature a superior catalytic efficacy over secondary amines with a variety of sterically hindered carbonyl compounds as substrates. The reaction proceeded well with various cyclic imines in 89-97 % ee and with various aryl methyl ketones in 85-98 % ee. Moreover, the aryl carbonyl of a Mannich product could be transformed to ketoxime, which further undergoes a Beckmann rearrangement to produce an amide compound while maintaining enantioselectivity.

Body Mass Index and Mortality: A 10-Year Prospective Study in China.

Although several studies have evaluated the role of body weight as a risk factor for mortality, most studies have been conducted in Western populations and the findings remain controversial. We performed a prospective study to examine the association between body mass index (BMI) and all-cause mortality in Yinzhou District, Ningbo, China. At baseline, 384,533 subjects were recruited through the Yinzhou Health Information System between 2004 and 2009. The final analysis was restricted to 372,793 participants (178,333 men and 194,460 women) aged 18 years and older. Cox proportional hazards models were used to estimate hazard ratios(HRs) and 95% confidence intervals(CIs). We found an increased risk of all-cause mortality among individuals with BMI levels <22.5-24.9, although several groups were not statistically significant-adjusted HRs for persons with BMIs of <15.0, 15.0-17.4, 17.5-19.9, and 20.0-22.4 were 1.61(95% CI: 1.17-2.23), 1.07(0.94-1.20), 1.04(0.98-1.10), 1.06(1.02-1.11), respectively. In the upper BMI range, subjects with BMIs of 25.0-34.9 had a reduced risk of all-cause mortality. Sensitivity analyses excluding smokers, those with prevalent chronic disease or those with less than four years of follow-up did not materially alter these results. Our findings provide evidence for an inverse association of BMI and mortality in this population.

[Body mass index and all-cause mortality in Asian adults: a meta-analysis].

OBJECTIVE: To perform a systematic review between all-cause mortality and body mass index (BMI) in Asian adults. METHOD: Relevant prospective studies that reported the relative risks (RRs) of all-cause mortality for community-based adults in Asia were identified by a literature search.PubMed and CNKI electronic databases were searched from inception through September 30, 2014, with language restrictions of English and Chinese. Data were extracted by 1 reviewer and then reviewed by 3 independent reviewers. The overall effect of varied levels of BMI and all-cause mortality were then pooled and analyzed.Potential sources of heterogeneity were detected by stratification analyses and sensitivity analyses. Publication bias was detected by funnel plot, Egger's test and Begg's test. RESULTS: Seventeen studies met the inclusion criteria; these studies included 1 769 369 individuals with 104 888 deaths. Random-effects summary all-cause mortality RRs was calculated. With the use of a BMI (in kg/m²) of 18.5~22.9 as the reference, the summary RRs were 1.39(95% CI: 1.31~1.47) for BMI less than 18.5 kg/m² , 0.88 (95% CI: 0.85~0.92) for BMI of 23.0~29.9 kg/m² and 1.14 (95% CI: 1.05~1.23) for BMI more than 30.0 kg/m². The RRs tended to be higher when weight and height were self-reported rather than measured. The RRs were higher when papers were published before the year 2005 rather than after the year 2006. Also, the RRs were higher when the quality scores were higher. Potential sources of heterogeneity were gender, the method of obtaining weight and height, geography, publication year and quality scores. There was no publication bias (P>0.05) in this meta-analysis. CONCLUSION: There was an increased risk of all-cause mortality for those both at the lower and higher level of BMI in Asian adults.

Asymmetric alkynylation of seven-membered cyclic imines by combining chiral phosphoric acids and Ag(I) catalysts: synthesis of 11-substituted-10,11-dihydrodibenzo[b,f][1,4]oxazepine derivatives.

Asymmetric alkynylation of seven-membered cyclic imine dibenzo[b,f][1,4]oxazepines is successfully achieved by combining chiral phosphoric acid and Ag(I) catalysts. Various arylacetylenes, conjugated enynes, and terminal 1,3-diynes are good substrates for this reaction, and aliphatic hexyne is also a suitable donor at elevated temperature. Optimization of this approach has provided a facile method to synthesize optically active 11-substituted-10,11-dihydrodibenzo[b,f][1,4]oxazepine derivatives containing a carbon-carbon triple bond with 63-99% ee. Subsequent transformations of the carbon-carbon triple bond for the heterocyclic products have been disclosed.

A highly enantioselective and regioselective organocatalytic direct Mannich reaction of methyl alkyl ketones with cyclic imines benzo[e][1,2,3]oxathiazine 2,2-dioxides.

A highly enantioselective direct Mannich reaction of methyl alkyl ketones with cyclic imines benzo[e][1,2,3]oxathiazine 2,2-dioxides, catalyzed by the combination of cinchona alkaloid derived primary amine and TFA, is disclosed. For unsymmetrical methyl alkyl ketones, it is favoured that specific regioselective addition to the imine substrates occurs at the less-substituted methyl group by steric control.

Enantioselective synthesis of cyclic sulfamidates via Pd-catalyzed hydrogenation.

Using Pd(CF3CO2) 2/(S,S)-f-binaphane as the catalyst, an efficient enantioselective synthesis of cyclic sulfamidates was developed via asymmetric hydrogenation of the corresponding cyclic imines in 2,2,2-trifluoroethanol at room temperature with high enantioselectivities (up to 99% ee).

Highly enantioselective Pd-catalyzed asymmetric hydrogenation of activated imines.

Pd/bisphosphines complexes are highly effective catalysts for asymmetric hydrogenation of activated imines in trifluoroethanol. The asymmetric hydrogenation of N-diphenylphosphinyl ketimines 3 with Pd(CF3CO2)/(S)-SegPhos indicated 87-99% ee, and N-tosylimines 5 could gave 88-97% ee with Pd(CF3CO2)/(S)-SynPhos as a catalyst. Cyclic N-sulfonylimines 7 and 11 were hydrogenated to afford the useful chiral sultam derivatives in 79-93% ee, which are important organic synthetic intermediates and structural units of agricultural and pharmaceutical agents.

Palladium-catalyzed asymmetric hydrogenation of functionalized ketones.

[reaction: see text]. A novel catalytic system for asymmetric hydrogenation of functionalized ketones has been developed using a Pd/bisphosphine complex as the catalyst in 2,2,2-trifluoroethanol. The reaction exhibits high enantioselectivity, and up to 92.2% ee was obtained.