Natural products are important sources for the discovery of new pesticides. Chemical synthesis and structural modification can lead to pesticides. Despite abundant research in fungicide discovery for crop protection, there is an emerging need for the development of novel antifungal agrochemicals. Herein, 39 diversified griseofulvin derivatives were effectively synthesized from the natural product griseofulvin by diversity-oriented synthesis through the reactions of demethylation, ammonolysis, methylation, nitration, acylation, reduction, and chlorination. Among them, 31 derivatives were novel. All structures were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HR-MS), and the antifungal activity was investigated against five phytopathogenic fungi. Compounds 5h and 5l had excellent activity against Botrytis cinerea (5h, IC50 = 17.29 ± 0.64 μg/mL) and Alternaria solani (5l, IC50 = 22.52 ± 0.79 μg/mL), respectively. Compound 9 exhibited the more promising activities against three target fungi, especially against Colletotrichum gloeosporioides (IC50 = 7.24 ± 0.66 μg/mL), which is obviously better than positive control hymexazol, thifluzamide, and parent compound griseofulvin. In addition, compound 10 showed significant and extensive activities against four target fungi Cytospora sp. (IC50 = 18.72 ± 0.35 μg/mL), C. gloeosporioides (IC50 = 31.39 ± 1.48 μg/mL), A. solani (IC50 = 40.82 ± 1.04 μg/mL), and Fusarium solani (IC50 = 36.81 ± 0.82 μg/mL). Unexpectedly, 11 and 12, the chlorinated products of compound 9, exhibited the most promising activity against C. gloeosporioides (IC50 = 4.48 ± 0.54 μg/mL for 11, 2.24 ± 0.76 μg/mL for 12). Furthermore, 12 showed remarkable activity against Cytospora sp. (IC50 = 5.85 ± 0.72 μg/mL). Additionally, in vivo antifungal activity against C. gloeosporioides, homology modeling, and docking analysis of 11, 12, and griseofulvin were conducted. All results indicated that 11 and 12 had potency as antifungal agents against C. gloeosporioides, and the modifications of the 2′ and 4′ positions of griseofulvin should be further explored for higher-activity lead compounds or potential agricultural fungicides.

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An efficient, tandem one-pot approach to synthesize multisubstituted 2-acylpyrroles from readily prepared N-tosyl triazoles and 2-hydroxymethylallyl carbonates is reported. The reaction proceeds via Rh(II)-catalyzed O–H insertion, [3,3]-sigmatropic rearrangement, Pd(0)-catalyzed oxidative addition, intramolecular cyclization, DBU-promoted E1cB elimination, double bond isomerization, and aromatization, enabling the disconnection and formation of multiple bonds in one reactor. The approach represents a highly regioselective way to access di-, tri-, and tetra-substituted NH pyrroles with high efficiency.

Dual Rh­(II)/Pd­(0) relay catalysis of N-sulfonyl triazoles and 2-hydroxymethylallyl carbonates has been developed, which affords N-sulfonyl pyrrolidines in moderate to good yields with high diastereoselectivities. The reaction proceeds via a relay mechanism involving O–H insertion onto the α-imino Rh­(II)–carbene, [3,3]-sigmatropic rearrangement, dipole formation through Pd(0)-catalyzed decarboxylation, and intramolecular N-allylation, leading to the formation of multiple bonds in a one-pot operation.