RhIII-Catalyzed Direct Heteroarylation of Unactivated C(sp3)-H with N-Heteroaryl Boronates.

Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.

RhIII-promoted directed C-H N-heteroarylation of 2-pyridones.

A catalytic protocol for the Cp*RhIII-promoted C6-selective N-heteroarylation of 2-pyridones with N-heterocyclic boronates has been successfully developed utilizing a removable pyridine auxiliary. This system features high efficiency with mild conditions and also tolerates ortho- and meta-substituted pyridines, pyrazoles, pyrimidine, non-substituted quinolines, thiophene and furan well. The easy synthetic approach could potentially be applied to construct heterocyclic drug molecules bearing 2-pyridone-heteroaryl motifs.

One-Pot Construction of Heteroarylation/Esterification Products of Acrylic Acids via Iridium(III)-Catalyzed C-H Activation.

A carboxylate-assisted iridium(III)-catalyzed regioselective C(sp2)-H heteroarylation/esterification reaction of acrylic acid is disclosed herein for the first time. This catalytic protocol tolerates various α-substituted, ß-substituted, and α, ß-disubstituted acrylic acids as well as heteroaromatic boronates well. The resulting 3,4-dihydro-2H-pyran-6-carboxylic acid derivative 3r highlighted the AIE-active luminophore with multiple emission signal properties and a high quantum yield of 28%, exhibiting the potential application of this methodology for the synthesis of nitrogen-containing organic functional materials.

RhIII-Catalyzed C-H N-Heteroarylation and Esterification Cascade of Carboxylic Acid with Organoboron Reagents and 1,2-Dichloroethane in One-Pot Synthesis.

A RhIII-catalyzed C(sp2)-H N-heteroarylation and esterification cascade of aryl carboxylic acids with N-heteroaromatic boronates and 1,2-dichloroethane in a one-pot synthesis has been disclosed. The strong coordinating ability of ortho- and meta-substituted pyridine boronates and pyrazoles as well as unsubstituted pyrimidine allows them to serve as the coupling partners. This protocol allows late-stage modification of the key precursor of roflumilast and compounds of pharmaceutical interest, which highlights the potential application of this synthetic method.

The synthesis of aryl-heteroaryl derivatives via the RhIII-catalyzed heteroarylation of arenes and heteroaromatic boronates.

An efficient RhIII-catalyzed strategy for constructing aryl-heteroaryl derivatives with removable ketoxime ether auxiliaries via direct C-H heteroarylation based on arenes and heteroaromatic boronates has been disclosed. This protocol could tolerate various pyridine, pyrimidine, pyrazole, thiophene, and furan heteroaromatic boronates well, providing the desired products with high reactivities and excellent regioselectivity. The easy synthetic accessibility may offer potential for application in the synthesis of heterocyclic drug molecules containing aryl-heteroaryl motifs.

RhIII-Catalyzed Direct Heteroarylation of C(sp3)-H and C(sp2)-H Bonds in Heterocycles with N-Heteroaromatic Boronates.

Herein, we disclose a RhIII-catalyzed heteroarylation of C(sp3)-H and C(sp2)-H bonds in heterocycles with organoboron reagents. This protocol displays high efficiency and excellent functional group tolerance. A range of heterocyclic boronates with strong coordinating atoms, including pyridine, pyrimidine, pyrazole, thiophene, and furan derivatives, can be extensively served as the coupling reagents. The direct heteroarylation method could supply potential application in terms of the synthesis of drug molecules with multiple heterocycles.

RhIII-Catalyzed C-H (Het)arylation/Vinylation of N-2,6-Difluoroaryl Acrylamides.

RhIII-catalyzed sp2 C-H cross-coupling of acrylamides with organoboron reactants has been accomplished using a commercially available N-2,6-difluoroaryl acrylamide auxiliary. A broad range of aryl and vinyl boronates as well as a variety of heterocyclic boronates with strong coordinating ability can serve as the coupling partners. This transformation proceeds under moderate reaction conditions with excellent functional group tolerance and high regioselectivity.

Potential Risks Associated with Japanese Encephalitis Prevalence in Shandong Province, China.

Japanese encephalitis (JE), which is caused by the Japanese encephalitis virus (JEV), is a zoonotic, vector-borne neurotropic disease that remains a major cause of viral encephalitis in Asia. JEV is spread to humans through mosquitoes, and its primary transmission vector is Culex tritaeniorhynchus. Mosquitoes were sampled from three collection sites: Hanzhuang town in Weishan County, Taibai Lake in Jining city, and Dongping Lake in Shandong Province, China. Pyrethroid insecticide resistance bioassays were conducted using adult mosquitoes. Cx. tritaeniorhynchus and C. pipiens pallens populations in Hanzhuang town and Dongping Lake showed resistance to pyrethroid insecticides, and populations in Taibai Lake showed incipient resistance. Coquillettidia ochracea populations in Hanzhuang town presented resistance as well, while in Taibai Lake, resistance was incipient. A total of 16,711 mosquitoes were collected, identified, and divided into 346 pools for JEV testing. Cx. tritaeniorhynchus had the advantage of being a local mosquito species. Overall, 31 (22.96) of the 135 pools of Cx. Tritaeniorhynchus were positive for JEV. The overall maximum likelihood estimates of Cx. tritaeniorhynchus, C. pipiens pallens, and Cq. ochracea indicated pooled infection rates of 5.29/1000 mosquitoes (95% confidence interval [CI] = 3.67-7.42), 1.60/1000 mosquitoes (95% CI = 0.82-2.85), and 6.39/1000 mosquitoes (95% CI = 0.39-32.23), respectively. There were no significant differences in the pooled infection rates between the districts. The resistance to pyrethroids has increased the difficulty in controlling the mosquito vectors, especially JEV-positive mosquitoes. Given the changes in the JEV transmission vectors, the spatial and temporal diversity and the dynamic variety of mosquito species, insecticide resistance and global warming have the potential to facilitate the transmission of JE to humans.

Rhodium-Catalyzed Direct Ortho C-H Arylation Using Ketone as Directing Group with Boron Reagent.

A general method for selective ortho C-H arylation of ketone, with boron reagent enabled by rhodium complexes with excellent yields, is developed. The transformation is characterized by the use of air-stable Rh catalyst, high monoarylation selectivity, and excellent yields of most of the substrates.

Epidemiological analysis of 133 malaria cases in Shanxian county, Shandong Province, China.

OBJECTIVE: To conduct an analysis of the epidemiological changes in malaria that have occurred in Shanxian county from 2002 to 2016. METHODS: A retrospective study was conducted and data were collected from web-based reporting system to explore the epidemiological characteristics in Shanxian county from 2002 to 2016. All individual case information was obtained from village malaria servicers organized by the local Shandong Institute of Parasitic Diseases. RESULTS: A total of 133 cases were identified as malaria in Shanxian county during this period, including 124 indigenous cases (93.2%) and 9 imported cases (6.8%). The 124 indigenous malaria cases were infected with Plasmodium vivax (P. vivax), whereas 7 of the 9 confirmed imported cases were infected with Plasmodium falciparum (P. falciparum), 1 was infected with Plasmodium ovale (P. ovale) and 1 patient was infected with P. falciparum mixed with P. vivax. The total number of malaria cases included 86 males (64.7%) and 47 females (35.3%). Age of the patients ranged from 1 to 83 years, although most (64.7%) infections occurred in the 21-to 60-year-old age group. Remarkably, 117 of the total malaria cases (98.0%) were reported from 2006 to 2011. The epidemic season was from June to October, with the peak occurring yearly from July to September. The most common occupation of the infected patients was farmer. In total, 58.1% of the cases occurred in 3 townships, namely, Fugang, Huanggang and Caozhuang. CONCLUSIONS: In Shanxian county, the local malaria incidence experienced an emerge-peak-control-eliminate status. However, due to the numbers of migrant labourers returning from Africa, imported cases were continuous and presented an increasing annual trend, which became a non-negligible and a significant impediment for malaria elimination. Therefore, the need to eliminate instances of malaria reintroduction to receptive malaria-free areas should drive strategies to align with the epidemiological changes.

Fine tuning of catalytic and sorption properties of metal-organic frameworks via in situ ligand exchange.

Metal-organic frameworks (MOFs) are gaining considerable attention not only because of their diverse structures but also due to their interesting properties and potential applications. However, fabrication of MOFs with desired structures and properties remains a great challenge. In this study, a strategy based on ligand exchange via single-crystal-to-single-crystal (SCSC) transformation has been undertaken, which can be used to achieve MOFs not available by direct synthesis and also to enrich the family of isoreticular MOFs. Direct X-ray crystallographic observation provides undoubted evidence that the pyrazine (pyz) ligand in [Cu3(L)2(pyz)(H2O)] (L3- = [1,1':3',1''-terphenyl]-4,4'',5'-tricarboxylate) was replaced by its derivatives without damaging the framework. Furthermore, the catalytic and sorption properties of the MOFs are able to be fine-tuned by introducing definite substituent group decorated on the pore surface. Thus, it is expected that the ligand exchange will be powerful for replacing linker molecules with others having desirable substituents, and as a result to afford desired MOFs.

Ligand-Promoted Rhodium(III)-Catalyzed ortho-C-H Amination with Free Amines.

Ligand development for rhodium(III)-catalyzed C-H activation reactions has largely been limited to cyclopentadienyl (Cp) based scaffolds. 2-Methylquinoline has now been identified as a feasible ligand that can coordinate to the metal center of Cp*RhCl to accelerate the cleavage of the C-H bond of N-pentafluorophenylbenzamides, providing a new structural lead for ligand design. The compatibility of this reaction with secondary free amines and anilines also overcomes the limitations of palladium(II)-catalyzed C-H amination reactions.

Rh(III)-Catalyzed meta-C-H Olefination Directed by a Nitrile Template.

A range of Rh(III)-catalyzed ortho-C-H functionalizations have been developed; however, extension of this reactivity to remote C-H functionalizations through large-ring rhodacyclic intermediates has yet to be demonstrated. Herein we report the first example of the use of a U-shaped nitrile template to direct Rh(III)-catalyzed remote meta-C-H activation via a postulated 12-membered macrocyclic intermediate. Because the ligands used for Rh(III) catalysts are significantly different from those of Pd(II) catalysts, this offers new opportunities for future development of ligand-promoted meta-C-H activation reactions.

Synthesis, structure, and magnetic and catalytic properties of metal frameworks with 2,2'-dinitro-4,4'-biphenyldicarboxylate and imidazole-containing tripodal ligands.

Based on 1,3,5-tris(1-imidazolyl)benzene (tib) and 2,2'-dinitro-4,4'-biphenyldicarboxylic acid (H2dnbpdc), four new metal-organic frameworks [M3(tib)(dnbpdc)3(H2O)2] [M = Mn (1), Cd (2)], [Zn3(tib)2(dnbpdc)2.5(Hdnbpdc)]·4DEF (3), and [Cd(tib)(dnbpdc)(H2O)]·DMF·H2O (4) (DEF = N,N-diethylformamide, DMF = N,N-dimethylformamide) were successfully synthesized. Isomeric 1 and 2 were unusual 8-connected uninodal three-dimensional (3D) frameworks with a point symbol of {3(3)·4(15)·5(9)·6}. Compound 3 was a (3,3,4,4)-connected 4-nodal 3D net with a point symbol of {4·6·8}2{4·6(2)}{4·8(5)}{6(2)·8(3)·10}, whereas 4 was a one-dimensional (1D) chain, which was further linked with neighboring 1D chains by hydrogen bonding interactions to give a 3D framework. It is interesting that 1 displayed ferromagnetic and antiferromagnetic interactions within the trinuclear Mn(ii) subunit. We also performed Knoevenagel condensation reactions catalyzed by activated 3 to demonstrate its heterogeneous catalytic property. Furthermore, the adsorption property of 3 was also investigated.

Ligand-Promoted Rh(III)-Catalyzed Coupling of Aryl C-H Bonds with Arylboron Reagents.

Rhodium(III)-catalyzed C-H arylation of arenes with phenylboronic acid pinacol esters has been achieved using a readily removable N-pentafluorophenylbenzamide directing group for the first time. The use of a bidentate phosphine ligand (Binap) significantly increased the yield of the cross-coupling of C-H bonds with organoboron reagents.

[Research Progress on the Molecular Mechanisms of Mosquito Innate Immunity].

As the important vector of the mosquito-borne diseases, mosquitos rely on their innate immune system against pathogens infection, which includes cellular immunity and humoral immunity. Both of them are interacted and coordinated, via the pattern recognition receptors, immune signaling, antimicrobial peptides, phenoloxidase-based melanization, phagocytosis, and so on. This paper reviews the research progress on the molecular mechanisms of mosquito innate immunity.

Resistance Level of Mosquito Species (Diptera: Culicidae) from Shandong Province, China.

This study describes the aquatic habitats, species composition, and the insecticide resistance level of the mosquito Culex pipiens pallens in Shandong Province, China. A cross-sectional survey of mosquito larval habitats was conducted from May to November 2014 to determine the species composition and larval abundance. Larvae were collected using the standard dipping technique, and a total of four habitat types were sampled. The fourth instar larvae of Cx. pipiens pallens collected in each habitat type were tested for resistance to five insecticides according to a WHO bioassay. A total of 7,281 mosquito larvae were collected, of which 399 (5.48%) were categorized as Anopheles mosquito larvae (An. sinensis), 6636 (91.14%) as culicine larvae (Cx. pipiens pallens, Cx. tritaeniorhynchus, Cx. halifaxii, and Cx. bitaeniorhynchus), 213 (2.93%) as Armigeres larvae, and 33 (0.45%) as Aedes larvae (Aedes albopictus). In addition, a total of 1,149 mosquito pupae were collected. Culex larvae were distributed in all habitats investigated. Tukeys HSD analysis showed that roadside drainages were the most productive habitat type for Culex larvae. Armigeres species were found only in drains, Aedes only in water tanks, and Anopheles in water that was comparatively clear and rich in emergent plants. Bioassay showed that the maximum resistance level of Cx. pipiens pallens was to deltamethrin, while it was lowest to plifenate. The productivity of various mosquitoes in different habitat types is very heterogeneous. It is particularly important to modify human activity and the environment to achieve effective mosquito vector control. For effective larval control, the type of habitat should be considered, and the most productive habitat type should be given priority in mosquito abatement programs.

Rh(iii)-catalyzed C-H olefination of N-pentafluoroaryl benzamides using air as the sole oxidant.

The oxidative olefination of a broad array of arenes and heteroarenes with a variety of activated and unactivated olefins has be achieved via a rhodium(iii)-catalyzed C-H activation reaction. The use of an N-pentafluorophenyl benzamide directing group is crucial for achieving catalytic turnovers in the presence of air as the sole oxidant without using a co-oxidant.

[Experimental study on cross-resistance of Culex pipiens pallens to 3 kinds of chemical pesticides].

OBJECTIVE: To understand the cross-resistance of Culex pipiens pallens to common pesticides, so as to provide the evidence for improving the application of chemical pesticides. METHODS: The IV instar larvae of DDVP-resistant, propoxur-resistant and cypermethrin-resistant strains as well as the sensitive strain of Culex pipiens pallens were collected to detect the resistance to DDVP, propoxur and cypermethrin based on the WHO bioassay method. RESULTS: The resistance coefficients of DDVP-resistant strain to DDVP, propoxur and cypermethrin were 14.47, 8.96 and 207.27 respectively. The resistance coefficients of propoxur-resistant strain to DDVP, propoxur and cypermethrin were 3.27, 6.93 and 8.65 respectively. The resistance coefficients of cypermethrin-resistant strain to DDVP, propoxur and cypermethrin were 2.93, 1.61 and 501.11 respectively. CONCLUSION: The resistance and cross-resistance could be generated during the long-term application of a single kind of chemical pesticide, and we should pay more attention to the varieties and dosages of them.

[Sequence analysis of ribosomal DNA internal transcribed spacer 2 of sympatric populations of Anopheles sinensis of different feeding preferences].

OBJECTIVE: To investigate the existence of genetic divergence of sympatric populations of Anopheles sinensis of different feeding preferences based on the rDNA-ITS2 sequence differences. METHODS: A large number of wild anopheles populations were trapped all night by man-baited net and calf-baited net that had been set up between high-density natural villages of An. sinensis populations and vector-breeding sites, from which two groups of An. sinensis were separated by morphological identification and brought back to the lab for conventional breeding. A large closed greenhouse which temperature and humidity was appropriate was selected as research settings of mark-release-recapture methods by female mosquitoes, in the center of which above An. sinensis populations baited by man and calf and respectively correspondingly marked by red and yellow phosphors were released in together, in each side of which An. sinensis were recaptured simultaneously by man-baited net and calf-baited net. An. sinensis populations trapped by man twice were brought back to the lab and bred with man-blood, correspondingly ones trapped by calf with calf-blood. Man-preferring and calf-preferring strains were screened respectively from An. sinensis which had been baited by man and calf by the mark-release-recapture methods after parent and F1 mosquitoes, and sequencing and aligning of both rDNA-ITS2 were conducted via PCR amplification. RESULTS: The recapture ratios of wild parental mosquitoes An. sinensis of man-preferring group by man-baited net and calf-baited net were 54.07% (339/627) and 45.93% (288/627) respectively, and ones of calf-preferring group by man-baited net and calf-baited net were 58.01% (409/705) and 41.99% (296/ 705) respectively. Two groups of parental mosquitoes trended towards selecting the original blood hosts in host-seeking preference (Χ2 = 19.42, P < 0.01). The recapture ratios of F1 mosquitoes An. sinensis of man-preferring group by man-baited net and calf-baited net were 63.43% (765/1 206) and 36.57% (441/1 206), and ones of calf-preferring group by man-baited net and calf-baited net were 68.22% (1 039/1 523) and 31.78% (484/1 523). Two groups of F1 mosquitoes had more significant characteristics of selecting the original blood hosts in host-seeking preference (Χ2 = 271.69, P < 0.01) and showed the genetic differentiation phenomenon, but the results of sequencing and aligning of the rDNA-ITS2 via PCR amplification showed no difference in base sequence between the two strains and both were 469 bp. CONCLUSIONS: The genetic divergence based on the rDNA-ITS2 sequence does not happen in An. sinensis sympatric populations of different feeding preferences.