Stereoselective Synthesis of Monofluoroalkenylphosphine Oxides via Photoinduced Decarboxylative Coupling of α-Fluoroacrylic Acids with P(O)H Compounds.

Herein, a practical and efficient method for synthesizing monofluoroalkenyl phosphine oxides via photoinduced decarboxylative/dehydrogenative coupling of α-fluoroacrylic acids with phosphine oxides and phosphonates has been developed. Various α-fluoroacrylic acids and P(O)H compounds containing relevant functional groups, including tetrafluorobenzene and pentafluorobenzene, were converted into corresponding products with excellent E-stereoselectivity in satisfactory yields. This method can be extended to achieve the synthesis of monofluoroalkenyl silanes under similar conditions.

[Research progress on camptothecin and its derivative nano-prodrugs based on tumor microenvironment response].

Nano-prodrug, one of the most widely used nano-formulation at present, has excellent efficacies in tumor treatment with high potential and clinical value. Camptothecin and its derivatives have broad prospects in the preparation of prodrugs for the treatment of tumors. Given the special microenvironment of tumors, including partial acidity, high concentration of reactive oxygen species, high concentration of glutathione and enzyme concentration, a large number of tumor microenvironment-responsive camptothecin and its derivative prodrugs were prepared. This paper classified them from the microenvironment response types and drug release characteristics, reviewed the research progress of camptothecin and its derivative prodrugs based on safety and clinical trials, and analyzed the existing problems and deficiencies, hoping to provide references for the development of camptothecin and its derivatives.

Synthesis of gem-difluoroalkenes via nickel-catalyzed allylic defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides.

A nickel-catalyzed defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides has been developed. Various substituted trifluoromethyl alkenes and epoxides were found to be suitable reaction substrates. This reaction enabled C(sp3)-C(sp3) bond construction through allylic defluorinative cross-coupling of trifluoromethyl alkenes under mild reaction conditions. This methodology was highly compatible with various sensitive functional groups, providing access to a diverse array of functionalized gem-difluoroalkene-containing alcohol compounds.

Base-free Ni-catalyzed Suzuki-type cross-coupling reactions of epoxides with boronic acids.

A Ni-catalyzed Suzuki-type cross-coupling of boronic acids with epoxides without an exogenous base and with broad substrate scope has been developed. The product selectivity of styrenyl epoxides is different from that of previous work. This methodology uses readily available starting materials to access a range of substituted alcohols, which are valuable feedstock chemicals.

Pd-Catalyzed decarboxylative cross-coupling reactions of epoxides with α,ß-unsaturated carboxylic acids.

A Pd-catalyzed decarboxylative cross-coupling of α,ß-unsaturated carboxylic acids with cyclic and acyclic epoxides has been developed. Both ß-monosubstituted and ß-disubstituted unsaturated carboxylic acids, as well as conjugated diene unsaturated carboxylic acids are suitable reaction substrates. Substituted homoallylic alcohols were obtained in moderate to good yields. The product was obtained as a mixture of diastereomers favoring the anti diastereomer of the cyclic epoxides. This work provides a method for the modification of complex organic molecules containing α,ß-unsaturated carboxylic acids.

Trisubstituted olefin synthesis via Ni-catalyzed hydroalkylation of internal alkynes with non-activated alkyl halides.

The stereoselective synthesis of tri-substituted alkenes is challenging. Herein, we report a Ni-catalyzed regio- and stereo-selective hydroalkylation of internal alkynes with non-activated alkyl halides. This method does not use any sensitive organometallic reagents and shows good functional group compatibility, which enables the efficient synthesis of many tri-substituted olefins from readily available coupling partners. It also provides a straightforward method for the modification of bioactive organic molecules.

New arylpyrazoline-coumarins: Synthesis and anti-inflammatory activity.

To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of new phenyl-pyrazoline-coumarin derivatives (4a∼4m) were designed and synthesized. Compounds 4a and 4b were determined by X-ray crystallography. All of the compounds have been screened for their anti-inflammatory activity characterized by evaluating their inhibition against LPS-induced IL-6 release. Among them, compound 4m showed the highest anti-inflammatory activity with inhibiting IL-6, TNF-α and nitric oxide (NO) production lipopolysaccharide (LPS)-stimulated. The further study showed that title compound 4m could significantly suppress expressions of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and the productions of IL-6, TNF-α, NO through NF-κB/MAPK signaling pathway. The anti-inflammatory activity of compound 4m was determined by carrageenan induced paw edema. Furthermore in vivo evaluation results indicated that compound 4m could inhibit AA-induced rat ankle joints.

Novel benzopyran derivatives and their therapeutic applications: a patent review (2009-2016).

INTRODUCTION: The benzopyran derivatives present a wide variety of biological activity and behaviour. At the same time the benzopyran derivatives support their use as therapeutic agents for multiple diseases. Their structural characteristics correlated to physicochemical properties seem to define the extent of the biological activity. Areas covered: This review summarizes new patents published on new benzopyran derivatives from 2009 to 2016. Expert opinion: Many benzopyran derivatives have vivo/vitro biological responses. Their clinical evaluation will be critical to assess therapeutic utility. The compounds containing benzopyran moiety is well defined as lead compounds for design of new more promising molecules.

Diarylpentadienone derivatives (curcumin analogues): Synthesis and anti-inflammatory activity.

A series of new (2E,4E)-1-(substitutedphenyl)-5-(substitutedphenyl)penta-2,4-dien-1-one derivatives were designed and synthesized. Compounds 3i, 3k were determined by X-ray. All of the compounds have been screened for their anti-inflammatory activity characterized by evaluating their inhibition against LPS-induced IL-6 and TNF-α release in cell RAW 264.7 stimulated with LPS. Compound 3i showed the highest anti-inflammatory activity on decreasing IL-6 and TNF-α. The further study showed that title compound 3i inhibited expression of proteins p-p65, iNOS, COX-2 LPS-induced. Immunofluorescence also revealed compound 3i could lightly reduce activation p65 in nuclei. These results indicate that compound 3i anti-inflammatory role may partly due to its inhibitory effect on the NF-κB signaling pathway.

Benzophenone-nucleoside derivatives as telomerase inhibitors: Design, synthesis and anticancer evaluation in vitro and in vivo.

Based on telomerase, thirteen novel phenstatin moiety linked stavudine derivatives (8a∼8e and 11a∼11f) were synthesized. The structures were determined by NMR and TOF-HRMS. The screening results showed that some compounds had better anti-cancer activity in vivo and in vitro. Among them, Compound 8d showed high inhibitory activity against telomerase and showed good antiproliferative activity against SGC-7901 cell with IC50 value 0.77 µM by inducing cell cycle arrest at G2 phase. It also could improve SGC-7901 cell apoptosis, mitochondrial membrane potential assay indicated that the dissipation of MMP might participate in apoptosis induced by title compound. In vivo studies showed that compound 8d displayed potent anticancer activity with inhibition tumor growth.