Enantioselective Access to Chiral 2,5-Diketopiperazines via Stereogenic-at-Cobalt(III)-Catalyzed Ugi-4CRs/Cyclization Sequences.

An asymmetric synthesis of chiral 2,5-diketopiperazines by the Ugi-4CR/cyclization is exhibited. The employment of catalytic anionic chiral Co(III) complexes delivered α-propiolyl aminoamides in high yields with excellent enantioselectivities (31 examples, up to 95% ee). The following treatment of Ugi-adducts with PPh3 leads to chiral 2,5-DKPs without significant loss of enantioselectivities (26 examples, up to 91% ee).

Enantioselective Ugi and Ugi-azide reactions catalyzed by anionic stereogenic-at-cobalt(III) complexes.

Ugi reactions and related variations are proven to be atom and step-economic strategies for construction of highly valuable peptide-like skeletons and nitrogenous heterocycles. The development of structurally diverse range of novel catalytic systems and the discovery of new approaches to accommodate a broader scope of terminating reagents for asymmetric Ugi four-component reaction is still in high demand. Here, we report a strategy that enables enantioselective Ugi four-component and Ugi-azide reactions employing anionic stereogenic-at-cobalt(III) complexes as catalysts. The key nitrilium intermediates, generated through the nucleophilic addition of isocyanides to the chiral ion-pair which consists of stereogenic-at-cobalt(III) complexes counteranion and a protonated iminium, are trapped by either carboxylic acids or in situ-generated hydrazoic acid, delivering α-acylamino amides and α-aminotetrazoles in good to excellent enantioselectivities (up to 99:1 e.r.).

Chiral N-Heterocyclic-Carbene-Catalyzed Cascade Asymmetric Desymmetrization of Cyclopentenediones with Enals: Access to Optically Active 1,3-Indandione Derivatives.

A chiral N-heterocyclic-carbene-catalyzed cascade asymmetric desymmetrization reaction of cyclopentenediones with enals has been successfully initiated, followed with tandem aldol annulation, aromatization, as well as sequential methylation. The reactions proceeded well under mild reaction conditions, with broad substrate scope and good functional group tolerance, providing a rapid access to highly functionalized chiral 2,2-disubstituted 1,3-indandione derivatives containing an all-carbon quaternary stereogenic center in moderate to good yields with high enantioselectivities.

Diastereodivergent synthesis of bispirooxindoles via asymmetric Friedel-Crafts/aldol cascade reaction: co-catalyst effects on diastereoselective outcomes.

A combination of metal- and organo-catalysts sequentially catalyzing the Friedel-Crafts/aldol tandem reaction between 3-pyrrolyl-oxindoles and isatin-derived ß,γ-unsaturated α-ketoesters has been reported, which leads to two types of diastereomeric enantio-enriched bispirooxindoles with three quaternary stereocentres and synthetically valuable functional groups in high yields with excellent enantioselectivity and diastereoselectivity.

Pd-Catalyzed Asymmetric Dearomative Cycloaddition for Construction of Optically Active Pyrroloindoline and Cyclopentaindoline Derivatives: Access to 3a-Aminopyrroloindolines.

Asymmetric dearomative [3 + 2] cycloaddition reactions of 3-nitroindoles with vinyl aziridine and vinyl cyclopropanes have been respectively successfully developed in the presence of a chiral box/Pd(0) complex. A series of enantiomerically enriched 3a-nitro-hexahydropyrrolo[2,3-b]indole and 8b-nitrohexahydrocyclopenta[b]indole derivatives containing three contiguous chiral centers are smoothly obtained in high yields with satisfactory regio-, chemo-, and enantioselectivity. Remarkably, the synthetic utility of this process was demonstrated through direct reductive amination and functionalization of the carbon-carbon double bond of the desired products.

Chiral Diphosphine-Palladium-Catalyzed Sequential Asymmetric Double-Friedel-Crafts Alkylation and N-Hemiketalization for Spiro-polycyclic Indole Derivatives.

An efficient cascade asymmetric Friedel-Crafts alkylation/N-hemiketalization/Friedel-Crafts alkylation reaction of 3-alkylindoles with oxindolyl ß,γ-unsaturated α-ketoesters has been developed in the presence of a chiral diphosphine-palladium(II) catalyst. A series of enantiomerically enriched spiro-polycyclic indole derivatives have been constructed in high yields with excellent enantioselectivities and diastereoselectivities.

A chiral ligand exchange CE system for monitoring inhibitory effect of kojic acid on tyrosinase.

A facile chiral ligand exchange capillary electrophoresis (CLE-CE) system with Zn(II)-L-alanine as the chiral selector in the presence of ß-cyclodextrin has been developed for enantioseparation of dansyl amino acids. The influence of the key factors, such as buffer pH, the ratio of Zn (II) to ligand, the concentration of ß-cyclodextrin and the concentration of the complex, were investigated in detail when D, L-Tyr and D, L-Thr were selected as the model analytes. The proposed method showed favorable quantitative analysis property of dansyl D, L-tyrosine with good linearity (r(2)≥0.999) and reproducibility (RSD≤3.8%), then, it was applied in studying the activity of tyrosinase through the determination of L-tyrosine concentration variation after being incubated with the enzyme. Further, the inhibitory efficiency of kojic acid and soy sauce on the tyrosinase was investigated. The IC50 of kojic acid obtained from the sigmoidal inhibitory curve was 21.35 µM. The results imply that the proposed CLE-CE system has the potential in exploring the activity of enzyme and screening the inhibitors of enzyme.

Anticoccidial activity of traditional Chinese herbal Dichroa febrifuga Lour. extract against Eimeria tenella infection in chickens.

The study was conducted on broiler birds to evaluate the anticoccidial efficacy of an extract of Chinese traditional herb Dichroa febrifuga Lour. One hundred broiler birds were assigned to five equal groups. All birds in groups 1-4 were orally infected with 1.5 × 10(4) Eimeira tenella sporulated oocysts and birds in groups 1, 2 and 3 were medicated with 20, 40 mg extract/kg feed and 2 mg diclazuril/kg feed, respectively. The bloody diarrhea, oocyst counts, intestinal lesion scores, and the body weight were recorded to evaluate the anticoccidial efficacy. The results showed that D. febrifuga extract was effective against Eimeria infection; especially 20 mg D. febrifuga extract/kg feed can significantly increase body weight gains and reduce bloody diarrhea, lesion score, and oocyst excretion in comparison to infected-unmedicated control group.

Anticoccidial effect of halofuginone hydrobromide against Eimeria tenella with associated histology.

Halofuginone (stenorol) has been used as an effective anticoccidial reagent for decades but very little is known about its mode of action. In this study, chickens were inoculated with Eimeria tenella oocysts on 14-day-old and medicated with halofuginone at days 0, 1, 2, 3, 4, 5 and 6 post inoculations (groups 0, 1, 2, 3, 4, 5 and 6, respectively). Chickens in group 7 were taken as challenge-unmedicated control and in group 8 unchallenged-unmedicated control. The survival rate, body weight gains (BWG), oocysts production, cecal scores, bloody diarrhea and histological examinations were analyzed to evaluate the anticoccidial efficacy of halofuginone and to initially elucidate its mechanisms. Results showed that halofuginone which acted as a coccidiostatic can significantly enhance the BWG, and decrease both the oocyst shedding and cecal destruction caused by E. tenella infection. The histological slide examination noted that halofuginone was effective when provided 0-2 days post inoculation but only partially effective when applied 3-7 days post infection. The second-generation schizonts treated with halofuginone appeared vacuolated and degenerated. It is concluded that halofuginone can inhibit the parasite's invasion of host cecal hypothetical cell at the early stages of life cycle and later disturb the parasite's development by vacuolation of the schizonts. The resulting abnormal schizonts could not divide into schizoites and were eventually eliminated by the host's immune response.

Adjuvant effect of ginsenoside-based nanoparticles (ginsomes) on the recombinant vaccine against Eimeria tenella in chickens.

An experiment was conducted to study the adjuvant effect of ginsomes on the recombinant profilin in coccidian-infected breeding birds. Three-day-old chickens were vaccinated with Eimeria tenella recombinant profilin antigen (10, 50, and 100 µg per chicken) with or without 50 µg ginsomes per chicken. The boost vaccination was carried out 14 days later. Two weeks after the booster, the chickens were challenged with 1.5 × 10(4) homologous sporulated oocysts. The specific antibody response, lymphocyte proliferation, and IL-1 release from lymphocyte were measured at 1-42 days after boost vaccination. Seven days post-challenge, the rate of survival, body weight gains (BWG) were examined then all chickens were sacrificed and lesion scores and oocysts per gram were monitored to evaluate the protective effects of the vaccination after challenge. Compared with the group of vaccinating with profilin only, groups of 50 and 100 µg antigen plus ginsomes significantly enhanced lymphocyte proliferation and IL-1 secretion. The profilin specific antibody level in the four vaccinated groups was significantly higher than in the control group and in groups vaccinated with profilin containing ginsomes than profilin only. In the groups vaccinated with profilin plus ginsomes, the BWG was significantly higher than that of group of profilin only, but there was no significant difference between profilin plus adjuvant ginsomes, diclazuril medicated and uninfected-unmedicated-unvaccinated control groups. The lesion scores in groups immunized with profilin plus ginsomes was significantly lower than that both of groups unimmunized-challenged-unmedicated control and group vaccinated with profilin only. Oocyst excretion in groups vaccinated with 50 or 100 µg profilin plus ginsomes was lower than that of groups vaccinated with profilin only. These results demonstrate that the adjuvant ginsomes can promote subunit vaccine to induce a strong immune response and protective effects.