Showing papers by "Yuxiu Liu published in 2014"
TL;DR: A new derivative, 14, with optimized physicochemical properties, obviously exhibited higher activities in vivo than Ribavirin and other derivatives; therefore, 14 can be used as a new lead structure for the development of anti-TMV drugs.
Abstract: Six known β-carboline, dihydro-β-carboline, and tetrahydro-β-carboline alkaloids and a series of their derivatives were designed, synthesized, and evaluated for their anti-tobacco mosaic virus (TMV) and fungicidal activities for the first time. All of the alkaloids and some of their derivatives (compounds 3, 4, 14, and 19) exhibited higher anti-TMV activity than the commercial antiviral agent Ribavirin both in vitro and in vivo. Especially, the inactivation, curative, and protection activities of alkaloids Harmalan (62.3, 55.1, and 60.3% at 500 μg/mL) and tetrahydroharmane (64.2, 57.2, and 59.5% at 500 μg/mL) in vivo were much higher than those of Ribavirin (37.4, 36.2, and 38.5% at 500 μg/mL). A new derivative, 14, with optimized physicochemical properties, obviously exhibited higher activities in vivo (50.4, 43.9, and 47.9% at 500 μg/mL) than Ribavirin and other derivatives; therefore, 14 can be used as a new lead structure for the development of anti-TMV drugs. Moreover, most of these compounds exhibit...
112 citations
TL;DR: Copper-catalyzed intramolecular trifluoromethylation of N-benzylacrylamides coupled with dearomatization was achieved and used to regiospecifically construct a variety of trifLUorometHylated 2-azaspiro[4.5]decanes bearing adjacent quaternary stereocenters under mild conditions in moderate to excellent yields.
67 citations
TL;DR: O-trifluoromethylaniline Schiff base (19) exhibited an eminent anti-TMV effect in the field and low toxicity to mice, suggesting it is a promising candidate for the inhibitor of plant virus.
Abstract: A series of aromatic gossypol Schiff bases have been successfully synthesized via a feasible chemical modification. The antiviral activity against tobacco mosaic virus (TMV) of these gossypol Schiff bases has been tested for the first time. The bioassay studies indicated most of these derivatives exhibited excellent anti-TMV activity, in which o-trifluoromethylaniline Schiff base (19) displayed the best antiviral activities. Furthermore, compound 19 exhibited an eminent anti-TMV effect in the field and low toxicity to mice. These results suggest it is a promising candidate for the inhibitor of plant virus.
67 citations
TL;DR: The field trials of antiviral efficacy against TMV (tobacco mosaic virus) showed that both compounds, especially compound 29, showed better activities than control plant virus inhibitors; the fungicidal results showed that compounds 6, 9, and 11 exhibited good fungicidal activities against 14 kinds of phytopathogens.
Abstract: According to our previous research on the antiviral activity of β-carboline and tetrahydro-β-carboline derivatives, using (1S,3S)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carbohydrazide (1) as a lead compound, series of novel tetrahydro-β-carboline derivatives containing acylhydrazone moiety were designed, synthesized, and first evaluated for their biological activities. Most of these compounds exhibited excellent antiviral activity both in vitro and in vivo. The in vivo inactivation, curative, and protection activities of compounds 8, 9, 12, 16, 28, 29, and 30 were much higher than that of ribavirin (37.6%, 39.4%, and 37.9% at 500 μg/mL) and the lead compound (40.0%, 42.3%, and 39.6% at 500 μg/mL). Especially, the in vitro and in vivo activities of compound 16 (36.9%, 33.6%, 30.2%, and 35.8%) at 100 μg/mL, which were very close to that of ribavirin (40.0% for in vitro activity) at 500 μg/mL. Compounds 9 and 29 were chosen for the field trials of antiviral efficacy against TMV (tobacco mosaic virus); the results exhibited that both compounds, especially compound 29, showed better activities than control plant virus inhibitors. At the same time, the fungicidal results showed that compounds 6, 9, and 11 exhibited good fungicidal activities against 14 kinds of phytopathogens. Additionally, compounds 3 and 23 exhibited moderate insecticidal activity against the four tested species of insects.
67 citations
TL;DR: The reaction mechanism was investigated in detail for the first time; DMAP·HCl and the acylating reagent directly formed N-acyl-4-(N',N'-dimethylamino)pyridine chloride, which was attacked by the nucleophilic substrate to form a transient intermediate that released the acyllation product and regenerated the DMAP ·HCl catalyst.
65 citations
TL;DR: Copper-mediated intramolecular trifluoromethylation of N-phenylcinnamamides coupled with cyclization and dearomatization was used to construct 1-azaspiro[4.5]decanes in moderate to high yields and with excellent regioselectivities and diastereoselectivity.
51 citations
TL;DR: By drawing the creation ideas of botanical pesticides, a series of tetrahydro-β-carboline-3-carboxylic acid derivatives were designed and synthesized, and first evaluated for their anti-TMV, fungicidal and insecticidal activities.
44 citations
TL;DR: In this article, a metal-free α-cyanation reaction of N-acyl/sulfonyl tetrahydroisoquinolines under mild conditions was developed.
Abstract: A highly efficient metal-free oxidative α-cyanation reaction of N-acyl/sulfonyl tetrahydroisoquinolines under mild conditions was developed. The reaction uses 2,2,6,6-tetramethylpiperidine N-oxide fluoroborate salt (T+BF4−) as the oxidant and trimethylsilyl cyanide as the source of the cyano group.
34 citations
TL;DR: A reaction sequence involving efficient generation of chiral homoallylic amine intermediates by asymmetric allylation of the corresponding tert-butanesulfinyl imine concluded that the pyrrolidine and piperidine rings were constructed by means of an intramolecular SN2 substitution reaction and a ring-closing metathesis reaction, respectively.
Abstract: A collective asymmetric synthesis of phenanthroindolizidine and phenanthroquinolizidine alkaloids (-)-antofine, (-)-cryptopleurine, (-)-tylophorine, and (-)-tylocrebrine was achieved by means of a reaction sequence involving efficient generation of chiral homoallylic amine intermediates by asymmetric allylation of the corresponding tert-butanesulfinyl imine. From these intermediates, the pyrrolidine and piperidine rings were constructed by means of an intramolecular SN2 substitution reaction and a ring-closing metathesis reaction, respectively. The unusual C5-methoxy-substituted phenanthrene moiety of (-)-tylocrebrine was generated by means of an InCl3-catalyzed cycloisomerization reaction of an o-propargylbiaryl compound.
31 citations
TL;DR: Two series of novel 2,4-diphenyl-1,3-oxazolines containing an oxime ether moiety were designed and synthesized via the key intermediate N-(2-chloro-1-(p-tolyl)ethyl)-2,6-difluorobenzamide and exhibited a promising application prospect as a new candicate for controlling spider mites in the field.
Abstract: Two series of novel 2,4-diphenyl-1,3-oxazolines containing an oxime ether moiety were designed and synthesized via the key intermediate N-(2-chloro-1-(p-tolyl)ethyl)-2,6-difluorobenzamide. The bioassay results showed that the target compounds with an oxime ether substituent at the para position of 4-phenyl exhibited excellent acaricidal activity against Tetranychus cinnabarinus in the laboratory. Moreover, all of the target compounds had much higher activities than etoxazole, as the ovicidal and larvicidal activities of the target compounds I-a–I-l and II-a–II-n against T. cinnabarinus were all over 90% at 0.001 mg L–1, but etoxazole gave only 30% and 40% respectively at the same concentration. The activity order of compounds with regard to acaricidal activity in vivo was almost consistent with their affinity activity with sulfonylurea receptor (SUR) of Blattella germanica in vitro, hence, it was supposed that the acaricidal mechanism of action of the target compounds was that they can bind with the site ...
31 citations
TL;DR: The bioassay result verified that both 2-benzylpyrroles 19 had varied degrees of insecticidal activity against oriental armyworm depending on the substituents on the benzene ring, but they did not give any acaricidal activity.
Abstract: Based on structures of insecticidal chlorfenapyr and antibiotic natural pyrrolomycins, a series of new 2-benzylpyrroles and 2-benzoylpyrroles (with or without ethoxymethyl group on the nitrogen of pyrrole) were designed and synthesized. These compounds or their parent compounds possess weak acidity and high lipophilicity, the two characteristic properties for uncouplers of oxidative phosphorylation; therefore, they are expected to have insecticidal and acaricidal activity. The bioassay result verified that both 2-benzylpyrroles 17 and 2-benzoylpyrroles 19 had varied degrees of insecticidal activity against oriental armyworm depending on the substituents on the benzene ring, but they did not give any acaricidal activity. Conversely, most N-alkylated compounds 18 and 20 exhibited both insecticidal activity and acaricidal activity, of which compound 18i [4-bromo-2-(2,4-dichlorobenzyl)-1-(ethoxymethyl) -5-(trifluoromethyl) -1H-pyrrole-3-carbonitrile] has IC50 as low as 10-20 mg L(-1) on both activities.
TL;DR: The structure-activity relationship showed that benzylpyrroles bearing shorter α-alkyloxy groups gave better activities against most of the insect species; the alkylation of pyrrole usually gave increased activity.
Abstract: On the basis of the structures of chlorfenapyr and dioxapyrrolomycin, a series of 2-benzylpyrroles with a hydroxyl, an alkyloxy, an acyloxy, an alkylsulfanyl, or an oxime moiety at the α-position of benzyl were designed and synthesized. Their insecticidal, acaricidal, and fungicidal activities were extensively investigated. The structure–activity relationship showed that benzylpyrroles bearing shorter α-alkyloxy groups gave better activities against most of the insect species; the alkylation of pyrrole usually gave increased activity. Among all compounds, (4-bromo-2-(α-(2,2,2-trifluoroethoxy)-4-chlorobenzyl)-1-(ethoxymethyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile) (5′j) exhibited the most outstanding insecticidal activities against oriental armyworm (IC50 = 10 mg L–1), diamondback moth (0.07 mg L–1), corn borer (50 mg L–1), and mosquito (0.04 mg L–1), which are very close to those of chlorfenapyr (5, 0.08, <25, and <0.025 mg L–1, respectively). In addition, some compounds also exhibited a broad or ...
TL;DR: The results showed that most of these compounds exhibited good to excellent anti-TMV activity, which indicated that the D and E rings of antofine may not be indispensable, which provides another new template for antiviral studies.
Abstract: On the basis of the interaction of antofine and tobacco mosaic virus (TMV) RNA, a series of phenanthrene and alkylamine chain containing antofine derivatives 1–41 were designed, synthesized, and systematically evaluated for their antiviral activity against TMV. The results showed that most of these compounds exhibited good to excellent anti-TMV activity, which indicated that the D and E rings of antofine may not be indispensable. Phenanthrene is important for these compounds, but not the more the better. Phenanthrene, benzene rings, and alkylamine chain containing compounds exhibited good antiviral activity. The optimum compounds, 10, 18, and 19, displayed higher activity than precursor antofine and commercial ribavirin, thus emerging as new lead compounds. The novel concise structure provides another new template for antiviral studies.
TL;DR: An efficient method to prepare 1'H-spiro[indoline-3,3'-quinoline]-2',4'-diones and their trifluoromethylated products was developed via a palladium-catalyzed Sonogashira coupling/Wacker-type oxypalladation/cyclization cascade reaction.
TL;DR: A concise and efficient enantioselective strategy to synthesize two typical phenanthroindolizidine alkaloids, 14-hydroxyantofine and antofine, was developed, featuring an asymmetric deprotonation/diastereoselectives carbonyl addition sequence during which the formation of a chiral C-13a center and connection of pyrrolidine and phenanthrene moieties were achieved efficiently in one step.
Abstract: A concise and efficient enantioselective strategy to synthesize two typical phenanthroindolizidine alkaloids, 14-hydroxyantofine and antofine, was developed, featuring an asymmetric deprotonation/diastereoselective carbonyl addition sequence during which the formation of a chiral C-13a center and connection of pyrrolidine and phenanthrene moieties were achieved efficiently in one step. The absolute configuration of the C-13a stereocenter can be delicately controlled by using different enantiomers of sparteine, both of which are commercially available.
TL;DR: Glycoconjugates of phenanthroindolizidine alkaloids targeting tobacco mosaic virus (TMV) RNA displayed significant higher activity than commercial ningnanmycin, and thus could be considered for novel therapy against plant virus infection.
Abstract: Glycoconjugates of phenanthroindolizidine alkaloids targeting tobacco mosaic virus (TMV) RNA were designed, synthesized, and evaluated for their antiviral activity against TMV for the first time. The glycoconjugation of $$(S)$$
-6-O-desmethylantofine (2) and 14-hydroxyltylophorines (3–6) was accomplished in three ways (O-glycosylation manner, using carbamoyloxy as linker arm, and using 1,2,3-triazole as linker arm) with three different sugar units (glucose, galactose, and mannose). The glycoconjugates showed improved water solubility and molecule polarity compared with phenanthroindolizidine alkaloids. The bioassay results showed that C6 was a suitable position for glycoconjugation and O-glycosylation can increase the antiviral activity of phenanthroindolizidine alkaloids indicating that the introduction of sugar units can improve the antiviral activity profile of glycoconjugates. Two O-glycosides of $$(S)$$
-6-O-desmethylantofine, (13aS)-6-O-
$$\upbeta $$
-d-galactopyranosyl-2,3-dimethoxyphenanthro [9,10-b]-11-indolizidinone (10) and (13aS)-6-O-
$$\upbeta $$
-d-mannopyranosyl-2,3-dimethoxyphenanthro [9,10-b]-11-indolizidinone (11) displayed significant higher activity than commercial ningnanmycin, and thus could be considered for novel therapy against plant virus infection.
TL;DR: A metal-free, environment friendly, easy-to-operate, and efficient method for the semisynthesis of sophocarpine from matrine has been developed in this paper.
TL;DR: It was found that two series of 2-alkyl-4-bromo-5-(trifluoromethyl)pyrrole-3-carbonitriles did not show much insecticidal activity, but compounds 4, 10, and 11 had very good fungicidal activities against Alternaria solani and Fusarium oxysporum.
TL;DR: Salification, the most commonly employed method for modifying physical‐chemical properties, did significantly increase antiviral activity, and different salt forms displayed different antiviral effect.
Abstract: A series of 7-methoxycryptopleurine derivatives 2-23 were prepared and evaluated for their antiviral activity against tobacco mosaic virus (TMV) for the first time. The bioassay results showed that most of these compounds exhibited excellent in vivo anti-TMV activity, of which 7-methoxycryptopleurine salt derivatives 16, 19, and 23 displayed significantly higher activity than 7-methoxycryptopleurine (1) and commercial ribavirin and ningnanmycin. Salification, the most commonly employed method for modifying physical-chemical properties, did significantly increase antiviral activity, and different salt forms displayed different antiviral effect. This study provides fundamental support for development and optimization of phenanthroquinolizidine alkaloids as potential inhibitors of plant virus.
TL;DR: In this article, the 4amination products of pyrrolidine-2,4-diones and 4-hydroxy-2-oxo,2,5-dihydro-1H-pyrrole-3-carboxylates (4) were prepared.
TL;DR: The target compounds were evaluated; their herbicidal, fungicidal, and insecticidal activities, and the preliminary bioassay data showed that some 3-cyanopyrrolidine-2,4-diones 2 gave good insecticidal activity, whereas some3-amido compounds 9 exhibited moderate to strong fungicidal activity against Pythium dissimile at 20 mg/L.
TL;DR: In this article, hydrazine moieties were introduced to the 3-position of pyrrolidine-2,4-dione scaffold of tenuazonic acid.
Patent•
24 Dec 2014TL;DR: In this article, a method for preparing β-carboline, dihydro-β-caroline, and tetrahydro- β-Caroline alkaloid derivatives and a method to use them for preventing and treating plant viruses, fungicides and insecticides.
Abstract: The present invention relates to β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives (I) and a method for preparing same and the use in the aspects of preventing and treating plant viruses, fungicides and insecticides. For the meaning of each group in formula (I) see the description. The β-carboline, dihydro-β-carboline and tetrahydro-β-carboline alkaloid derivatives of the present invention show a particularly ourstanding anti-plant virus activity, and also have fungicidal and insecticidal activities.
TL;DR: In this paper, the authors investigated the reaction mechanism for the first time; DMAP·HCl and the acylating reagent directly formed N-acyl-4-(N′,N′-dimethylamino)pyridine chloride, which was attacked by the nucleophilic substrate to form a transient intermediate that released the acyation product and regenerated the DMAP-HCl catalyst.
Abstract: 4-(N,N-Dimethylamino)pyridine hydrochloride (DMAP·HCl), a DMAP salt with the simplest structure, was used as a recyclable catalyst for the acylation of inert alcohols and phenols under base-free conditions. The reaction mechanism was investigated in detail for the first time; DMAP·HCl and the acylating reagent directly formed N-acyl-4-(N′,N′-dimethylamino)pyridine chloride, which was attacked by the nucleophilic substrate to form a transient intermediate that released the acylation product and regenerated the DMAP·HCl catalyst.
TL;DR: A metal-free, environment friendly, easy-to-operate, and efficient method for the semisynthesis of sophocarpine from matrine has been developed in this article.
Abstract: A metal-free, environment friendly, easy-to-operate, and efficient method for the semisynthesis of sophocarpine from matrine has been developed in an overall yield of 91%. The route features a controllable and efficient oxidation of thioether to sulfoxide by 2-iodoxybenzoic acid (IBX) in water.
Patent•
24 Dec 2014TL;DR: In this article, a method for preparing β-carboline, dihydro- β -carboline and tetrahydro-β -caroline alkaloid derivatives for use as fungicide, insecticide and in preventing and treating plant virus infections.
Abstract: The present invention relates to β -carboline, dihydro- β -carboline and tetrahydro- β -carboline alkaloid derivatives (I), a method for preparing the same and their use as fungicide, insecticide and in preventing and treating plant virus infections. For the meaning of each group in formula (I) see the description. The β -carboline, dihydro- β -carboline and tetrahydro- β -carboline alkaloid derivatives of the present invention show a particularly pronounced anti-plant virus activity, and also have fungicidal and insecticidal activities.
TL;DR: In this article, a palladium-catalyzed Sonogashira coupling/Wacker-type oxypalladation/cyclization cascade reaction was used for trifluoromethylation.
Abstract: An efficient method to prepare 1′H-spiro[indoline-3,3′-quinoline]-2′,4′-diones and their trifluoromethylated products was developed via a palladium-catalyzed Sonogashira coupling/Wacker-type oxypalladation/cyclization cascade reaction. The amount of water in the reaction system played an important role in the in situ trifluoromethylation reaction, and the trifluoromethylation exhibited excellent molecular self-induced stereoselectivity.
TL;DR: In this paper, the methacrylamide analogue of the acrylamides (Ia) fails to give the corresponding 3-azaspiro[5.5]undecane derivative.
Abstract: Transformation of the methacrylamide analogue of the acrylamide (Ia) fails to give the corresponding 3-azaspiro[5.5]undecane derivative.
TL;DR: In this paper, a stereoselective synthesis of (+)-antofine (I) and (+)-14-hydroxyantofines (II) is presented, where the synthesis is based on a linear combination of the synthesis of + and −14.
Abstract: A stereoselective synthesis of (+)-antofine (I) and (+)-14-hydroxyantofine (II) is presented.