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Two new pairs of chlorinated orsellinic aldehyde enantiomers acresorcinols A and B (1a/1b and 2a/2b), and three orsellinic aldehydes, acresorcinols C−E (3−5) were discovered from the extract of the deep-sea-derived fungus Acremonium sclerotigenum LW14. Their structures, including absolute configurations, were experimentally elucidated by spectroscopic analysis, NMR calculations with DP4+ probability analysis, and ECD calculations. Compounds 1 and 2 exemplify the first reported chlorinated orsellinic aldehydes, characterised by a distinctive 6/5−5 tricyclic core structure with a bridged framework. Acresorcinol C (3) was a rare carbon-bridged resorcinol dimer via a methylene bridge. The bioassay results showed that all compounds exhibited antifungal activities against Cryptococcus gattii 3271G1 at 32 μg/mL. Compounds 1−3 showed antifungal effects against C. gattii 3271G1, displaying MIC values of 8, 16, and 16 µg/mL, respectively.

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