Showing papers by "Yuxiu Liu published in 2019"
TL;DR: A protocol for direct visible-light-mediated Minisci C–H alkylation of heteroarenes with unactivated alkyl halides using molecular oxygen as an oxidant at room temperature is reported.
Abstract: Herein, we report a protocol for direct visible-light-mediated Minisci C–H alkylation of heteroarenes with unactivated alkyl halides using molecular oxygen as an oxidant at room temperature. This mild protocol is compatible with a wide array of sensitive functional groups and has a broad substrate scope. Notably, functionalization of (iso)quinolines, pyridines, phenanthrolines, quinazoline, and other heterocyclic compounds with unactivated primary, secondary, and tertiary alkyl halides proceeds smoothly under the standard conditions. The robustness of this protocol is further demonstrated by the late-stage functionalization of complex nitrogen-containing natural products and drugs.
92 citations
TL;DR: Mechanistic studies revealed that the catalytic behavior of CuI photocatalyst generated in situ was consistent with that of preformed [Cu(dmp)(xantphos)]BF4.
57 citations
TL;DR: A new catalytic activation mode that combines proton-coupled electron transfer (PCET) with spin-center shift (SCS) and enables C─H alkylation of heteroarenes using ketones and aldehydes as alkyl radical equivalents is described.
Abstract: The polar nature of the C═O bond commonly allows it to undergo direct attack by nucleophiles at the electrophilic carbon atom in which ketones and aldehydes act as alkyl carbocation equivalents. In contrast, transformations in which ketones and aldehydes act as alkyl radical equivalents (generated in carbonyl carbon) are unknown. Here, we describe a new catalytic activation mode that combines proton-coupled electron transfer (PCET) with spin-center shift (SCS) and enables C─H alkylation of heteroarenes using ketones and aldehydes as alkyl radical equivalents. This transformation proceeded via reductive PCET activation of the ketones and aldehydes to form α-oxy radicals, addition of the radicals to the N-heteroarenes to form C─C bonds, and SCS to cleave the C─O bonds of the resulting alcohols. This mild protocol represents a general use of abundant, commercially available, ketones and aldehydes as latent alkyl radical equivalents.
55 citations
TL;DR: This study provides important information for the research and development of pimprinine alkaloids as novel antiviral agents and lays the foundation for simplifying the structure of these alkalids.
Abstract: Plant viral diseases cause tremendous decreases in crop yield and quality. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. A series of pimprinine alkaloids and their derivatives were prepared and identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) were systematically investigated for the first time. Most of the compounds exhibited higher antiviral activities than ribavirin. Compounds 5l, 9h, and 10h, which had similar or higher antiviral activities than ningnanmycin (perhaps the most widely used antiviral agent at present), emerged as new antiviral pilot compounds. This systematic structure-activity-relationship research lays the foundation for simplifying the structure of these alkaloids. The ring-open products, acylhydrazones 9a-9u, were also found to possess good antiviral activities. Moreover, all the synthesized compounds displayed broad-spectrum fungicidal activities. This study provides important information for the research and development of pimprinine alkaloids as novel antiviral agents.
49 citations
TL;DR: A new C(sp3)-H monofluoroalkenylation reaction involving cooperative visible-light photoredox catalysis and hydrogen-atom-transfer catalysis to afford products generated by selective hydrogen abstraction and radical-radical cross-coupling was described.
40 citations
TL;DR: A mild protocol for direct visible-light-initiated Giese addition of unactivated alkyl iodides to electron-poor olefins (Michael acceptors) with catalysis by decacarbonyl dimanganese, Mn2(CO)10, an inexpensive earth-abundant-metal catalyst is reported.
28 citations
TL;DR: Current research has laid a foundation for the application of nortopsentin analogues in plant protection by indicating that these compounds may play an antiviral role by aggregating viral particles to prevent their movement in plants.
Abstract: Plant diseases seriously endanger plant health, and it is very difficult to control them. A series of nortopsentin analogues were designed, synthesized, and evaluated for their antiviral activities...
28 citations
25 citations
TL;DR: The protocol uses environmentally benign persulfate as a stoichiometric oxidant and does not require high temperatures or large excesses of either of the substrates, making the procedure suitable for late-stage C-H alkylation of complex molecules.
Abstract: Herein, we report a mild protocol for metal-, photocatalyst-, and light-free Minisci C-H alkylation reactions of N-heteroarenes with alkyl oxalates derived from primary, secondary, and tertiary alcohols. The protocol uses environmentally benign persulfate as a stoichiometric oxidant and does not require high temperatures or large excesses of either of the substrates, making the procedure suitable for late-stage C-H alkylation of complex molecules. Notably, several pharmaceuticals and natural products could be functionalized or prepared with this protocol, thus demonstrating its utility.
25 citations
TL;DR: This research again proved that the substituent type at the para site of the 4-phenyl moiety has a decisive role on the biological activity and insecticidal spectrum.
Abstract: Sulfimides and sulfoximines are highly relevant for medicinal chemistry and crop protection, as the resulting products can reveal interesting bioactivities. Herein, we report the design and synthesis of a series of novel 2,4-diphenyl-1,3-oxazolines containing sulfiliminyl and sulfoximinyl moieties. The acaricidal and insecticidal activities of the new compounds were evaluated and indicated that these compounds exhibited excellent acaricidal activities against spider mite larvae and eggs. The LC50 values of 6a-7, 6b-3, 6b-4, 6c-2, and 6c-4 against spider mite larvae were about 4 to 6 times lower than that of the commercial insecticide etoxazole (0.0221 mg L–1), and the LC50 value of 6a-4 against spider mite eggs was 0.0006 mg L–1, which was 10 times lower than that of etoxazole (0.0063 mg L–1). At the same time, most of the compounds showed insecticidal activity though their structure–activity relationships that were different. Oxazolines containing an N-cyano sulfiliminyl moiety at the para position of th...
23 citations
TL;DR: The first visible-light-induced trifluoromethylation and monofluoroalkenylation of simple alkenes via a challenging radical-radical cross-coupling step was achieved.
Abstract: The first visible-light-induced trifluoromethylation and monofluoroalkenylation of simple alkenes via a challenging radical-radical cross-coupling step was achieved. This method provided a mild, step-economical and redox-neutral route to privileged two different fluorinated difunctionalized allyl compounds. The utility of this method is illustrated by late-stage modification of medically important molecules.
TL;DR: A new radical-mediated intramolecular arene C(sp2)-H amidation of 3-phenylpropanamides or [1,1'-biphenyl]-2-carboxamides was developed to prepare a series of 3,4-dihydro-2(1H)-quinolinone and phenanthridone derivatives in moderate to excellent yields.
Abstract: A new radical-mediated intramolecular arene C(sp2)–H amidation of 3-phenylpropanamides or [1,1′-biphenyl]-2-carboxamides was developed to prepare a series of 3,4-dihydro-2(1H)-quinolinone and phenanthridone derivatives in moderate to excellent yields (33–94%). Spirolactams could also be obtained using this protocol.
TL;DR: This is the first report of the use of N-phenyl amidoxime esters as amidinyl radical precursors, and the first use of substituted benzene rings asAmidinyl radical acceptors, to overcomes the shortcomings of the traditional methods for synthesis of 2-substituted benzimidazoles.
Abstract: We have developed a new method for the synthesis of 2-substituted benzimidazoles via amidinyl radicals generated by visible-light-promoted reduction of N-phenyl amidoxime esters in the presence of an iridium photocatalyst. This is the first report of the use of N-phenyl amidoxime esters as amidinyl radical precursors, and the first use of substituted benzene rings as amidinyl radical acceptors. This method widens the application range of substrates and overcomes the shortcomings of the traditional methods for the synthesis of 2-substituted benzimidazoles, which requires harsh reaction conditions, involves difficult-to-prepare substituted o-phenylenediamine substrates, and produces acidic waste.
TL;DR: In this paper, under mild conditions with persulfate as a stoichiometric oxidant, benzylsilanes and heteroatom substituted silanes undergo homolytic cleavage to form C(sp3)-centered radicals that can participate in C-H alkylation reactions with N-heteroarenes.
Abstract: Herein we report that under oxidative conditions, benzylsilanes and heteroatom substituted silanes undergo homolytic cleavage to form C(sp3)-centered radicals that can participate in C–H alkylation reactions with N-heteroarenes. These reactions take place under mild conditions with persulfate as a stoichiometric oxidant and do not require a metal, a photocatalyst, light, or high temperature, making the reactions suitable for late-stage C–H alkylation of complex molecules. The utility of the method was demonstrated by the preparation or functionalization of several structurally complex drugs and natural products.
TL;DR: A protocol for alkylation reactions of C(sp3)-H bonds with diacyl peroxides by means of a process involving cross-coupling between an alkyl radical and an α-aminoalkyl radical is described.
TL;DR: 2,4-diphenyl-1,3-oxazolines containing a sulfonate moiety at the para-position of the 4-phenyl group are designed and synthesized to address pest-related constraints on global agricultural production and deserve further attention as a pesticide candidate.
Abstract: With the ultimate goal of addressing pest-related constraints on global agricultural production, we used combination principles to design and synthesize 2,4-diphenyl-1,3-oxazolines containing a sulfonate moiety at the para-position of the 4-phenyl group. The target compounds, which have strong affinity for lipids and can be expected to traverse cell membranes, were characterized by 1H and 13C NMR spectroscopy and high-resolution mass spectrometry. Their activities against the larvae and eggs of carmine spider mites (Tetranychus cinnabarinus) were determined by a leaf-dipping method and compared with the activity of the commercial acaricide etoxazole. Most of the test compounds displayed good ovicidal and larvicidal activities. In particular, a tert-butylphenyl-substituent compound possessed better larvicidal activity (LC50 = 0.022 ± 0.009 mg/L) and ovicidal activity (0.044 ± 0.020 mg/L) than etoxazole (0.091 ± 0.051 and 0.095 ± 0.059 mg/L, respectively). Given its outstanding bioactivities, this compound ...
TL;DR: The analogues 3a-3v of natural product cerbinal were synthesized from genipin by an efficient and practical method under additive-free condition and suggested that the cyclopenta[c]pyridines obtained by modifications of cerbinals at position 2 are very significant for anti-TMV activity, and yet which were exceptionally less active for the insecticidal activities.
Abstract: Owing to the changing needs of agriculture, the exploration of new pest control agents remains as critical as ever. The analogues 3a–3v of the natural product cerbinal were synthesized from genipin...
TL;DR: A one step-economical protocol for the synthesis of functionalized iminoisobenzofurans by means of visible-light-induced intramolecular cyclization reactions of 2-alkyl-substituted benzamides is developed.
TL;DR: The 3-cayno moiety on pyrazole ring was essential for the high insecticidal activities against bean aphid, diamondback moth and Oriental armyworm, while the 3-carbimidate moiety was crucial to the excellent high insecticide activities against mosquito.
TL;DR: This mild protocol for photoredox-mediated Minisci C-H alkylation reactions of N-heteroarenes tolerated a broad range of func-tional groups and could therefore be used for late-stage functionalization of complex nitrogen-containing natural products and drugs.
Abstract: We developed a protocol for photoredox-mediated Minisci C–H alkylation reactions of N-heteroarenes in which readily available tert-butyl peroxyacetate acts as a radical relay precursor to generate ...
TL;DR: An organo-photoredox-based protocol using 2,2-diethoxyacetic acid as the acetal source to achieve acetalation of alkynyl bromides to afford various alkyny acetal products has potential utility for the synthesis of aldehydes by further protonization.
Abstract: Herein, we report an organo-photoredox-based protocol using 2,2-diethoxyacetic acid as the acetal source to achieve acetalation of alkynyl bromides to afford various alkynyl acetal products. In addition to arylethynyl bromides, substrates bearing heteroaryl rings (thiophene, pyridine, and indole) smoothly gave the corresponding acetalation products. This mild protocol has potential utility for the synthesis of aldehydes by further protonization.
TL;DR: A co-drug of 14-hydroxytylophorine, a phenanthroindolizidine derivative with remarkable antiproliferative activity, and dichloroacetate, a known inhibitor of pyruvate dehydrogenase kinase is developed, which reverses the Warburg effect and renders tumour cells with a proliferative disadvantage.
Abstract: Co-drug, or mutual-prodrug, is a drug design approach consisting of covalently linking two active drugs so as to improve the pharmacokinetics and/or pharmacodynamics properties of one or both drugs. Co-drug strategy has proven good success in overcoming undesirable properties such as absorption, poor bioavailability, nonspecificity, and gastrointestine tract (GIT) side effects. In this work, we successfully developed a co-drug of 14-hydroxytylophorine, a phenanthroindolizidine derivative with remarkable antiproliferative activity, and dichloroacetate, a known inhibitor of pyruvate dehydrogenase kinase. Dichloroacetate steers tumour cell metabolism from glycolysis back to glucose oxidation, which in turn reverses the Warburg effect and renders tumour cells with a proliferative disadvantage. The obtained co-drugs retained the cytotoxicity of 14-hydroxytylophorine. However, they showed similar unselectivity towards normal cells.
TL;DR: Compound R- 12, the cyanomethyl ether of 6-desmethylantofine, exhibited significant anti-cancer activity and inhibited the proliferation of a panel of 30 cancer cell lines including 2 multi-drug-resistant cell lines with an average IC50 value of 18.7 nM, which suggests that R-12 is a promising new anti- cancer agent.
TL;DR: A number of boron-based analogues of (R)-6-O-desmethylantofine have been synthesised and showed interesting cytotoxicity against a panel of cancerous cell lines attested by a cancer cell growth-inhibitory potency (GI50) as low as 30 nM.
Abstract: Phenanthroindolizidines are naturally occurring alkaloids mainly isolated from different species of Asclepiadaceae. These alkaloids are characterized by an excellent anticancer activity against a very wide range of cancerous cell lines including those who are multi drug resistant. Nevertheless, phenanthroindolizidines are associated with sever neurotoxicity that prevented any candidate from this family to pass the clinical trials. A number of boron-based analogues of (R)-6-O-desmethylantofine have been synthesised. Their physochemical properties were evaluated, same as their in-vitro antiproliferative activity. The pinacol boronate ester derivative (3) showed interesting cytotoxicity against a panel of cancerous cell lines attested by a cancer cell growth-inhibitory potency (GI50) as low as 30 nM.