Showing papers by "Yuxiu Liu published in 2018"

Marine-Natural-Product Development: First Discovery of Nortopsentin Alkaloids as Novel Antiviral, Anti-phytopathogenic-Fungus, and Insecticidal Agents.

Abstract: Nortopsentin alkaloids were found to have potent antiviral, anti-phytopathogenic-fungus, and insecticidal activities for the first time. Antiviral-activity tests revealed that these compounds were very sensitive to substituents, so a series of nortopsentin derivatives were designed, synthesized, and systematically evaluated for their antiviral activities against TMV, their fungicidal activities, and their insecticidal activities on the basis of a structural-diversity-derivation strategy. Compounds 2e (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 50, 59, and 56%, respectively, at 500 μg/mL) and 2k (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 60, 58, and 52%, respectively, at 500 μg/mL), with excellent antiviral activities and good physicochemical properties, emerged as new lead compounds for novel-antiviral-agent development. Further fungicidal-activity tests revealed that these alkaloids displayed broad-spectrum fungicidal activities. Comp...

Synthesis of gem‐Difluorinated Spiro‐γ‐lactam Oxindoles by Visible‐Light‐Induced Consecutive Difluoromethylative Dearomatization, Hydroxylation, and Oxidation

Abstract: Described herein is a protocol for visible-light-induced consecutive synthesis of gem-difluorinated spiro-γ-lactam oxindoles under mild conditions by means of a process involving sequential radical difluoromethylative dearomatization, hydroxylation, and oxidation. The protocol features high chemo- and regioselectivity, good functional group tolerance, and easy scalability. Several of the functionalized spirooxindole products showed good fungicidal activity, suggesting that they have potential agrochemical applications.

N-Arylamines Coupled with Aldehydes, Ketones, and Imines by Means of Photocatalytic Proton-Coupled Electron Transfer

Abstract: A photoredox-catalyzed umpolung strategy for coupling reactions between aldehydes, ketones, imines, and N-arylamines is reported. These reactions proceed by a Bronsted acid-activated proton-coupled electron transfer pathway, and the protocol was used to synthesize a broad scope of 1,2-amino alcohols and vicinal diamines, both of which are common motifs in biologically active natural products, pharmaceutically active molecules, and ligands.

Design, Synthesis, and Biological Activity of β-Carboline Analogues Containing Hydantoin, Thiohydantoin, and Urea Moieties

Abstract: A series of novel β-carboline derivatives was designed by combining the anti-tobacco mosaic virus (TMV) lead compound tetrahydro-β-carboline ester with the hydantoin, thiohydantoin, and urea motifs. These derivatives were synthesized from tetrahydro-β-carboline ester via a structural diversity-oriented synthesis in one step, and their biological activities were evaluated. Most of the derivatives exhibited anti-TMV activity higher than that of commercial plant virucide ribavirin, such as compounds 2, 4, 5, 7, 9, 15, 16, 19, and 21. Compared with the lead compounds, some of these derivatives showed good insecticidal activity against Plutella xylostella and Culex pipiens pallens. At the same time, these derivatives also showed broad-spectrum fungicidal activity. The systematic study provides strong evidence that the hydantoin, thiohydantoin, and urea motifs of these molecules can improve and modulate the activities of the analogues of natural products.

Dehydrogenation of N‐Heterocycles by Superoxide Ion Generated through Single‐Electron Transfer

Abstract: Nitrogen-containing heteroarene motifs are found in numerous pharmaceuticals, natural products, and synthetic materials. Although several elegant methods for synthesis of these compounds through dehydrogenation of the corresponding saturated heterocycles have been reported, some of the methods are hampered by long reaction times, harsh conditions, and the need for catalysts that are not readily available. This work reports a novel method for dehydrogenation of N-heterocycles. Specifically, O2.- generated in situ acts as the oxidant for N-heterocycle substrates that are susceptible to oxidation through a hydrogen atom transfer mechanism. This method provides a general, green route to N-heteroarenes.

Marine Natural Products for Drug Discovery: First Discovery of Kealiinines A-C and Their Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents.

Abstract: Leucetta alkaloid kealiinines A–C and kealiinine B derivatives were designed, synthesized, and characterized on the basis of NMR and HR-MS The anti-TMV and antiphytopathogenic fungus activities of these alkaloids were evaluated for the first time Kealiinine B exhibited a higher anti-TMV activity than kealiinines A and C Kealiinine B derivatives 2m (inhibitory rates: 68, 66, and 71% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) and 2y (inhibitory rates: 69, 64, and 63% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) showed significantly higher antiviral activity than ningnanmycin (inhibitory rates: 56, 56, and 58% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively), thus emerging as new lead compounds for novel antiviral agent development Structure–activity relationship research provided the basis for structural simplification of these alkaloids Further fungicidal activity tests reveal

Design, Synthesis, and Antitobacco Mosaic Virus Activity of Water-Soluble Chiral Quaternary Ammonium Salts of Phenanthroindolizidines Alkaloids

Abstract: To study the influence of the substituent at the N-10 position on antiviral activity, the chiral quaternary ammonium salt derivatives of R- and S-tylophorine were designed, synthesized, and evaluated for antiviral activity against tobacco mosaic virus (TMV). The bioassay results indicated that most of the designed structural analogues showed good in vivo anti-TMV activity, among which propargyl quaternary ammonium salt compound S-7b showed the best anti-TMV activities (80.5%, 77.6%, 76.6%, 82.1%) at 500 μg/mL both in vitro and in vivo in the laboratory. In the field trials of antiviral efficacy against TMV, S-7b as well exhibited better activities than control plant virus inhibitors. The stability of compound S-7b was obviously increased, and its solubility was more than 500-times higher than that of S-tylophorine. Therefore, chiral quaternary ammonium salt S-7b was expected to be developed as a promising candidate as an inhibitor of plant virus.

Leveraging botanical resources for crop protection: the isolation, bioactivity and structure-activity relationships of lycoris alkaloids.

Abstract: Background Lycoris aurea (L' Herit.) Herb (Amaryllidaceae) is a native pesticide in China. The ethanolic extract of Lycoris aureate bulbs, the total alkaloids of L. aurea bulbs and the main alkaloids of L. aurea bulbs were systematically investigated as part of a novel project to study their antiviral, fungicidal (phytopathogenic) and insecticidal activities. We also prepared 18 lycorine derivatives and evaluated their bioactivities. Results Lycorine had excellent larvicidal activity against Plutella xylostella (LC50 = 10.6 mg L-1 ) and was also effective during a field trial. It also showed good inhibitory activity against tobacco mosaic virus (TMV) and good fungicidal activity against Phytophthora capsici (EC50 = 7.76 mg L-1 ). Compounds 13 and 15 exhibited good anti-TMV activity, excellent fungicidal activity against Rhizoctonia cerealis (EC50 = 6.78 mg L-1 ) and excellent larvicidal activity against Culex pipiens pallens (LC50 at 0.1-0.25 mg L-1 ). Conclusion Lycorine was identified as the main active component of L. aurea bulbs and showed potential for field application against P. xylostella. The activities of compounds 13 and 15 make them excellent candidates for new lead compounds in novel pesticide research. This study provides the basis for developing these alkaloids into potential agrochemicals. © 2018 Society of Chemical Industry.

Discovery of Glycosylated Genipin Derivatives as Novel Antiviral, Insecticidal, and Fungicidal Agents

Abstract: A series of novel genipin glycoside derivatives incorporating 11 glycosidic moieties at either the 1 or 10 position of genipin were designed and synthesized. These compounds exhibited moderate to excellent inhibitory activities against tobacco mosaic virus. Especially, the in vitro and in vivo activities of compounds 6e, 7c, 7d, 7f, 7h, and 7i were comparable to that of ribavirin. In particular, compound 7c, the mannosyl derivative of genipin at the 10 position, showed the best activity. The series of genipin glycosyl derivatives also displayed fungicidal activities against 14 kinds of phytopathogenic fungi, especially for Rhizoctonia cerealis and Sclerotinia sclerotiorum. Moreover, compound 6h exhibited good insecticidal activity against diamondback moth; compounds 7b, 7c, and 7g exhibited moderate insecticidal activity against three kinds of Lepidoptera pests (oriental armyworm, cotton bollworm, and corn borer); and compound 7e showed excellent larvacidal activities against mosquito.

C(sp3)–H Azidation Reaction: A Protocol for Preparation of Aminals

Abstract: We report a protocol for the synthesis of N, N- and N, O-aminals via direct azidation of sp3 C-H bonds of substrates with an α-nitrogen or α-oxygen atom. A broad range of tetrahydroisoquinolines, tetrahydro-β-carbolines, and cyclic benzyl ethers gave high yields under mild conditions. The protocol could be carried out on a gram scale without a decrease in the yield, and the aminal products could be readily transformed into complex aminals.

Naamines and Naamidines as Novel Agents against a Plant Virus and Phytopathogenic Fungi.

Abstract: Naamines, naamidines and various derivatives of these marine natural products were synthesized and characterized by means of nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The activities of these alkaloids against a plant virus and phytopathogenic fungi were evaluated for the first time. A benzyloxy naamine derivative 15d displayed excellent in vivo activity against tobacco mosaic virus at 500 μg/mL (inactivation activity, 46%; curative activity, 49%; and protective activity, 41%); its activities were higher than the corresponding activities of the commercial plant virucide ribavirin (32%, 35%, and 34%, respectively), making it a promising new lead compound for antiviral research. In vitro assays revealed that the test compounds exhibited very good antifungal activity against 14 kinds of phytopathogenic fungi. Again, the benzyloxy naamine derivative 15d exhibited broad-spectrum fungicidal activity, emerging as a new lead compound for fungicidal research. Additional in vivo assays indicated that many of the compounds displayed inhibitory effects >30%.

Arylpyrrole and fipronil analogues that inhibit the motility and/or development of Haemonchus contortus in vitro.

Abstract: Due to widespread drug resistance in parasitic nematodes, there is a need to develop new anthelmintics. Given the cost and time involved in developing a new drug, the repurposing of known chemicals can be a promising, alternative approach. In this context, we tested a library (n = 600) of natural product-inspired pesticide analogues against exsheathed third stage-larvae (xL3s) of Haemonchus contortus (barber's pole worm) using a whole-organism, phenotypic screening technique that measures the inhibition of motility and development in treated larvae. In the primary screen, we identified 32 active analogues derived from chemical scaffolds of arylpyrrole or fipronil. The seven most promising compounds, selected based on their anthelmintic activity and/or limited cytotoxicity, are arylpyrroles that reduced the motility of fourth-stage larvae (L4s) with significant potency (IC50 values ranged from 0.04 ± 0.01 μM to 4.25 ± 0.82 μM, and selectivity indices ranged from 10.6 to 412.5). Since the parent structures of the active compounds are uncouplers of oxidative phosphorylation, we tested the effect of selected analogues on oxygen consumption in xL3s using the Seahorse XF24 flux analyser. Larvae treated with the test compounds showed a significant increase in oxygen consumption compared with the untreated control, demonstrating their uncoupling activity. Overall, the results of the present study have identified natural product-derived molecules that are worth considering for chemical optimisation as anthelmintic drug leads.

An Unprecedented Cyano-Induced Sodium Nitrite-Catalyzed C(sp3)-H and C(sp2)-H Coupling Reaction

Abstract: Aim and Objective: During the investigation of sodium nitrite-catalyzed oxidative coupling reaction of aryls, an unprecedented C(sp2)-H and C(sp3)-H coupling of substituted 2-aryl acetonitrile was found. The structure of the coupled product was confirmed by 1H and 13C NMR spectroscopy and high-resolution mass spectrometry (HRMS), and comparison of its derivatives with known compounds. The effects of methoxy group in the benzene ring on the reaction were evaluated. The optimized reaction conditions are summarized as follows: CF3SO3H/substrate = 1.5 equiv., NaNO2/substrate = 0.3 equiv., CH3CN as solvent. 2-(4-Methoxyphenyl)acetonitrile and 2-(3,4,5- trimethoxyphenyl)acetonitrile could also generate C(sp2)-H and C(sp3)-H coupling. The coupling reaction occurred as a typical radial mechanism. An unprecedented cyano-induced, NaNO2-catalyzed oxidative C(sp3)-H and C(sp2)-H coupling was reported. The reaction proceeded under very mild conditions, using O2 in the air as terminal oxidant. The unique oxidative manner might provide more inspiration for the development of intriguing oxidative coupling reactions.