CF3‐ or HCF2‐substituted cyclopropanes are of great interest in pharmaceutical chemistry and agrochemistry, and thus significant efforts have been directed towards the development of efficient methods for the installation of these motifs. This Minireview summarizes recent efforts for the construction of CF3‐ or HCF2‐substituted cyclopropanes. CF3‐cyclopropanes are usually synthesized by a transition‐metal‐catalyzed cyclopropanation of alkenes with a trifluoromethylcarbene generated in situ from a diazocompound, CF3CHN2 or CF3C(Ar)N2. The synthesis of HCF2‐cyclopropanes remains largely unexplored. Some difluoromethylcarbene reagents have been developed, such as HCF2CHN2, Ph2S+CH2CF2H TfO−, and difluoroacetaldehyde N‐triftosylhydrazone (DFHZ‐Tfs), and cyclopropanation of alkenes with these reagents could also occur by transition metal catalysis. These protocols may find great utility in the synthesis of biologically active molecules.

BackgroundIsoliquiritigenin (ISL), a natural flavonoid isolated from the root of licorice (Glycyrrhiza uralensis), has shown various pharmacological properties including anti-oxidant, anti-inflammatory and anti-cancer activities. MicroRNAs (miRNAs), a class of small non-coding RNAs, have been reported as post-transcriptional regulators with altered expression levels in melanoma. This study aims to investigate the anti-melanoma effect of ISL and its potential mechanism.MethodsWe investigated the effect of ISL on the proliferation and apoptosis of melanoma cell lines with functional assays, such as CCK-8 assay, colony formation assay and flow cytometry. The protein level of apoptosis related genes were measured by western blotting. High-throughput genome sequencing was used for screening differentially expressed miRNAs of melanoma cell lines after the treatment of ISL. We performed functional assays to determine the oncogenic role of miR-301b, the most differentially expressed miRNA, and its target gene leucine rich repeats and immunoglobulin like domains 1 (LRIG1), confirmed by bioinformatic analysis, luciferase reporter assay, western blotting and immunohistochemical assay in melanoma. Immunocompromised mouse models were used to determine the role of miR-301b and its target gene in melanoma tumorigenesis in vivo. The relationship between miR-301b and LRIG1 was further verified in GEO data set and tissue specimens.ResultsFunctional assays indicated that ISL exerted significant growth inhibition and apoptosis induction on melanoma cells. MiR-301b is the most differentially expressed miRNA after the treatment of ISL and significantly downregulated. The suppressive effect of ISL on cell growth is reversed by ectopic expression of miR-301b. Intratumorally administration of miR-301b angomir enhances the inhibitory effect of ISL on tumor growth in vivo. Bioinformatic analysis showed that miR-301b may target LRIG1, miR-301b suppresses the luciferase activity of reporter constructs containing 3’UTR of LRIG1 as well as the expression level of LRIG1. And the anti-cancer effect of ISL is mitigated when LRIG1 is silenced in vivo and in vitro. Analysis of the melanoma samples obtained from patients shows that LRIG1 is negatively correlated with miR-301b.ConclusionsISL may inhibit the proliferation of melanoma cells by suppressing miR-301b and inducing its target LRIG1.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0844-x) contains supplementary material, which is available to authorized users.

The molybdenum-catalyzed asymmetric ring-closing metathesis of the various Cs -symmetric (π-arene)chromium substrates provides the corresponding bridged planar-chiral (π-arene)chromium complexes in excellent yields with up to >99 % ee. With a bulky and unsymmetrical substituent, such as N-indolyl or 1-naphthyl, at the 2-positions of the η(6) -1,3-diisopropenylbenzene ligands, both biaryl-based axial chirality and π-arene-based planar chirality are simultaneously induced in the products. The axial chirality is retained even after the removal of the dicarbonylchromium fragment, and the chiral biaryl/heterobiaryl compounds are obtained with complete retention of the enantiopurity.

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Planar-chiral (h 6 -arene)chromium complexes are useful chiral scaffolds in asymmetric synthesis, and have found widespread application as chiral ligands for asymmetric catalysis, or as chiral building blocks for natural product syntheses. [1] Typical methods for the preparation of enantiomerically enriched planar-chiral (arene)chromium species are based either on the optical resolution of racemates [2] or on stereoselective transformations, which include diastereoselective complexation, [3] diastereo-or enantioselective ortho-lithiation by utilizing a chiral directing group or a chiral base, [4] and diastereo-or enantioselective nucleophilic addition/hydride abstraction. [5] Whereas these methods require a stoichiometric amount of chiral reagents or auxiliaries, asymmetric catalysis is an attractive and effective alternative for preparing optically active (h 6 -arene)chromium complexes. Since the first report on such a catalytic process by Uemura et al. in 1993, [6] only a handful of examples of the desymmetrization of prochiral (arene)chromium substrates have been reported by Gotov and Schmalz, [7] Kündig and co-workers, [8,9] and Uemura and co-workers [10,11] .Recently, we reported the preparation of phosphinechelate (h 6 -arene)chromium complexes by Ru-catalyzed ringclosing metathesis. [12] We also demonstrated that Mo-catalyzed asymmetric ring-closing metathesis (ARCM) was highly effective for the asymmetric synthesis of the various planarchiral ferrocenes. [13] Thus, we are interested in controlling the planar chirality of (h 6 -arene)chromium complexes by ARCM. [14,15] Indeed, the kinetic resolution of racemic (h 6 -1,2-disubstituted benzene)chromium complexes proceeds efficiently in the presence of a chiral Mo-alkylidene species to give the planar-chiral chromium complexes with excellent enantiomeric purity. Furthermore, a highly enantiomerically enriched (h 6 -bromoarene)chromium complex that was prepared by using the present method is an excellent precursor to various planar-chiral (arene)chromium derivatives. A (phos-phinoarene)chromium species was derived from the (h 6bromoarene)chromium complex and applied as a chiral ligand in Rh-catalyzed asymmetric reactions, which achieved excellent enantioselectivity of up to 99.5 %.The (h 6 -arene)chromium complexes (rac-1) that were used in this study contain an h 6 -(2-substituted alkenylbenzene) ligand, which constructs the planar-chiral environment upon coordination to the chromium atom, and an alkenylphosphine ligand. The chiral catalysts were screened by using racemic [(h 6 -2-methylstyrene)Cr(CO) 2 (methallyldiphenylphosphine)] (1 a) as a prototypical substrate. The asymmetric reactions were carried out in benzene at 40 8C in the presence of an appropriate chiral Mo catalyst (10 mol %), which was generated in situ from the Mo precursor [(pyrrolyl) 2 Mo( = CHCMe 2 Ph)(=NC 6 H 3 -2,6-iPr 2 )] and an axially chiral biphenol derivative (Table 1). [16] Under these conditions, the Mo catalyst that was generated with (R)-L1 [17a] gave the ARCM product 2 a...

Cryptotanshinone (CPT) is an efficacious acne treatment, while niosomal hydrogel is a known effective topical drug delivery system that produces a minimal amount of irritation. Three-dimensional (3D) printing technologies have the potential to improve the field of personalized acne treatment. Therefore, this study endeavored to develop a 3Dprinted niosomal hydrogel (3DP-NH) containing CPT as a topical delivery system for acne therapy. Specifically, CPT-loaded niosomes were prepared using a reverse phase evaporation method, and the formulation was optimized using a response surface methodology. In vitro characterization showed that optimized CPT-loaded niosomes were below 150 nm in size with an entrapment efficiency of between 67 and 71%. The CPT-loaded niosomes were added in a dropwise manner into the hydrogel to formulate CPT-loaded niosomal hydrogel (CPT-NH), which was then printed as 3DP-CPT-NH with specific drug dose, shape, and size using an extrusion-based 3D printer. The in vitro release behavior of 3DP-CPT-NH was found to follow the Korsmeyer-Peppas model. Permeation and deposition experiments showed significantly higher rates of transdermal flux, Q 24 , and CPT deposition (p < 0.05) compared with 3D-printed CPT-loaded conventional hydrogel (3DP-CPT-CH), which did not contain niosomes. In vivo anti-acne activity evaluated through an acne rat model revealed that 3DP-CPT-NH exhibited a greater anti-acne effect with no skin irritation. Enhanced skin hydration, wide inter-corneocyte gaps in the stratum corneum and a disturbed lipid arrangement may contribute towards the enhanced penetration properties of CPT. Collectively, this study demonstrated that 3DP-CPT-NH is a promising topical drug delivery system for personalized acne treatments.

Summary of main observation and conclusionCF3S, CF3 and HCF2 groups have been identified as valuable functionalities for drug development. Despite significant accomplishments in the trifluoromethylthiolation, trifluoromethylation and difluoromethylation reactions, directly converting common functional groups into CF3S, CF3 or HCF2 groups is still highly desirable. Described here is the dehydroxylative trifluoromethylthiolation, trifluoromethylation and difluoromethylation of alcohols promoted by a R3P/ICH2CH2I system. All of these dehydroxylative reactions were achieved under mild conditions via the activation of the hydroxyl group by the R3P/ICH2CH2I system. A wide substrate scope and good functional group tolerance were observed.

A series of phosphoric acid (PA) doped imidazolium poly­(phenylene oxide) (PPO) membranes with different methylimidazole (MeIM) contents were prepared to tailor the performance of solid-state membranes. First, brominated poly­(phenylene oxide) (BPPO) was synthesized by methyl bromination. Then BPPO was reacted with MeIM and doped with PA. The process was confirmed by Fourier transform infrared spectroscopy and 13C NMR. The PA absorption ability of the imidazolium poly­(phenylene oxide) (PPO-MeIM) membranes changed with increasing MeIM content. PPO-MeIM membrane showed the best proton conductivity of 6.79 × 10–2 S cm–1 at 0% relative humidity, the highest mechanical strength of 4.8 MPa at the molar ratio of 4:10 (M-3#) at 30 °C, and high power density of 260 mW cm–2 without additional humidification at 160 °C. Results indicated that incorporation of an appropriate amount of MeIM groups can achieve the best proton conduction performance and mechanical properties.