To promote the discovery and development of new fungicides, a series of novel pyrazol-5-yl-benzamide derivatives were designed, synthesized by hopping and inversion of amide groups of pyrazole-4-carboxamides, and evaluated for their antifungal activities. The bioassay data revealed that compound 5IIc exhibited an excellent in vitro activity against Sclerotinia sclerotiorum with an EC50 value of 0.20 mg/L, close to that of commercial fungicide Fluxapyroxad (EC50 = 0.12 mg/L) and Boscalid (EC50 = 0.11 mg/L). For Valsa mali, compound 5IIc (EC50 = 3.68 mg/L) showed a significantly higher activity than Fluxapyroxad (EC50 = 12.67 mg/L) and Boscalid (EC50 = 14.83 mg/L). In addition, in vivo experiments proved that compound 5IIc has an excellent protective fungicidal activity with an inhibitory rate of 97.1% against S. sclerotiorum at 50 mg/L, while the positive control Fluxapyroxad showed a 98.6% inhibitory effect. The molecular docking simulation revealed that compound 5IIc interact with TRP173, SER39, and ARG43 of succinate dehydrogenase (SDH) through a hydrogen bond and p−π interaction, which could explain the probable mechanism of the action between compound 5IIc and target protein. Also, the SDH enzymatic inhibition assay was carried out to further validate its mode of action. These results demonstrate that compound 5IIc could be a promising fungicide candidate and provide a valuable reference for further investigation.

Total syntheses of (±)-walsucochin B and (±)-walsucochinoids M and N have been achieved from farnesyl bromide. The key steps of the synthetic sequence are the titanocene-mediated radical cyclization and base-induced cycloaromatization for the rapid construction of the 6/6/5/6-fused tetracyclic skeleton. Importantly, a Cu-mediated remote C−H hydroxylation reaction has been developed to site-selectively install the oxygen function at the C-7 position of the target molecules, thus solving the biggest challenge for the synthesis of the compounds.Letter pubs.acs.org/OrgLett

On the basis of the structure of nicotlactone A (L1), a series of novel α-methylene-γ-butyrolactone derivatives B1–B43 were designed and synthesized by structure simplification and active fragment replacement strategies, and their antiviral and antifungal activities were evaluated. The bioassay studies indicated that many target compounds possessed good to excellent antiviral activity against tobacco mosaic virus (TMV) and some of these compounds exhibited specific antifungal activities against Valsa mali and Fusarium graminearum. Compound B32 exhibited the best anti-TMV activity (inactivation effect, 88.9%; protection effect, 65.8%; curative effect, 52.8%) in vivo at 500 mg/L, which is significantly higher than that of commercial virucides ribavirin and ningnanmycin. The inhibition effect of compound B32 was also visualized by the inoculation test using green fluorescent protein (GFP)-labeled TMV. The preliminary antiviral mechanism of compound B32 was investigated. Transmission electron microscopy (TEM) showed that compound B32 could destroy the integrity of virus particles. Then, molecular docking and isothermal titration calorimetry (ITC) analysis further demonstrated that compound B32 exhibited a strong binding affinity to the TMV coat protein with a dissociation constant (K d) of 3.06 μM, superior to ribavirin. Thus, we deduced that compound B32 may interfere with the self-assembly of TMV particles by binding TMV coat protein (CP). In addition, compound B28 showed good in vitro activity against F. graminearum with an inhibition rate of 90.9% at 50 mg/L, which was greater than that of fluxapyroxad (59.1%) but lower than that of the commercial fungicide carbendazim (96.8%). The present study provides support for the application of these α-methylene-γ-butyrolactone derivatives as novel antiviral and antifungal agents in crop protection.

Catalyzed by the complex generated in situ from iridium and the chiral ferrocene ligand, tert-butyl (4-oxo-4-arylbutyl)carbamate substrates were deprotected and then reductively cyclised to form 2-substituted arylpyrrolidines in a one-pot manner, in which the intramolecular reductive amination was the key step. A range of chiral 2-substituted arylpyrrolidines were synthesised in up to 98% yield and 92% ee.

A one-pot N-Boc deprotection and catalytic intramolecular reductive amination protocol for the preparation of enantiomerically pure tetrahydroisoquinoline alkaloids is described. The iodine-bridged dimeric iridium complexes displayed superb stereoselectivity to give tetrahydroisoquinolines, including several key pharmaceutical drug intermediates, in excellent yields under mild reaction conditions. Three additives played important roles in this reaction: Titanium(IV) isopropoxide and molecular iodine accelerated the transformation of the intermediate imine to the tetrahydroisoquinoline product; p-toluenesulfonic acid contributed to the stereocontrol.