A series of novel quinazolin‐4(3H)‐one derivatives were efficiently synthesized starting from isatoic anhydride. First, reaction of isatoic anhydride and amines in H2O at room temperature afforded 2‐aminobenzamides. Then, CuBr/Et3N promoted reaction of 2‐aminobenzamides and different aryl isothiocyanates in DMF at 80° afforded the title compounds in good yield.

The plant endophyte Chalara sp. is able to biotransform the epigenetic modifier vorinostat to form unique, aniline-containing polyketides named chalanilines. Here, we sought to expand the chemical diversity of chalaniline A-type molecules by changing the aniline moiety in the precursor vorinostat. In total, twenty-three different vorinostat analogs were prepared via two-step synthesis, and nineteen were incorporated by the fungus into polyketides. The highest yielding substrates were selected for large-scale precursor-directed biosynthesis and five novel compounds, including two fluorinated chalanilines, were isolated, purified, and structurally characterized. Structure elucidation relied on 1D and 2D NMR techniques and was supported by low- and high-resolution mass spectrometry. All compounds were tested for their bioactivity but were not active in antimicrobial or cell viability assays. Aminofulvene-containing natural products are rare, and this high-yielding, precursor-directed process allows for the diversification of this class of compounds.

The reaction between N,2-diarylhydrazinecarbothioamide (generated from arylhydrazines and aryl isothiocyanates) and malononitrile in the presence of iodine/triethylamine in N,N-dimethylformamide at 80 °C afforded novel pyrazoles, 5-amino-1-aryl-3-(arylamino)-1H-pyrazole-4-carbonitriles, in good yields. In this strategy, iodine served as a versatile desulfurizing agent, efficiently promoting the cyclization reaction.

C halanil ine B [1-anili no-2 ,8-di h ydroxy-3-(hydroxymethyl)xanthone], an antibiotic previously isolated from vorinostat-treated Chalara sp., was prepared in 7 steps from 2hydroxyxanthone by a route incorporating regioselective oxidative transformations (bromination at C1/C3, ketone directed Pd(II)catalyzed hydroxylation at C8), installation of the C1-anilino moiety by a regioselective Buchwald-Hartwig amination reaction from 1,3dibromo-2,8-dimethoxyxanthone, and late-stage hydroxymethylation at C3 using a Stille cross-coupling. Biological evaluation of deshydroxymethylchalaniline B (1-anilino-2,8-dihydroxyxanthone) revealed MIC values of 8 μg mL −1 (25 μM) against both methicillin resistant S. aureus and B. subtilis.

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