Structurally Diverse Duclauxins from a Coral-Derived Talaromyces sp. and Insight into Determining the Configuration at C-1 of Heptacyclic Duclauxins by 1H NMR.

Abstract

A chemical investigation of the coral-derived fungus Talaromyces sp. TJ403-AL05 led to the isolation of 18 duclauxin analogues (1-18), 14 of which, taladuxins A-N (1-14), are new and consist of the first example of duclauxin fused with one 1,6-dioxaspiro[4.5]decan-2-one moiety (1), as well as its biosynthetic product (2), and 12 6/6/6/5/6/6/6 heptacyclic derivatives (3-14). Comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, DP4+ probability analyses, single-crystal X-ray diffraction, and vibrational circular dichroism (VCD) calculations were employed to characterize their structures and revise the published structure of verruculosin B. An efficient ¹H NMR method was established to discriminate 1R and 1S configurations at C-1 of 6/6/6/5/6/6/6 heptacyclic duclauxins according to chemical shift differences of diastereotopic methylene H₂-11 or H₂-12 (Δδ_H-11 or Δδ_H-12). Compounds 4, 7-8, 13-15, and 18 exhibited moderate inhibition of Arabidopsis thaliana 4-hydroxyphenylpyruvate dioxygenase (AtHPPD), with IC₅₀ values ranging from 17.1 to 71.3 μM.