Eutypetides A–E, Structurally Intriguing Polyketides Formed by Intramolecular [4+2] Cycloaddition from Marine-Derived Fungus Eutypella sp. F0219

Abstract

Comprehensive Summary:Four polycyclic ten-membered lactones possessing unprecedented 10/6/5 tricyclic ring skeleton, named eutypetides A–D ( 1– 4), and an intriguing polyketide containing a hexahydroisobenzofuran-1(3 H)-one motif, named eutypetide E ( 5) were isolated from the marine-derived fungus Eutypella sp. F0219, together with three new related biosynthetic polyketides eutypetides F–H ( 6– 8). The absolute configurations of 1– 5 were unequivocally determined by single-crystal X-ray diffraction analyses (Cu Kα), modified Mosher’s method and electronic circular dichroism (ECD) calculations. Eutypetides G ( 7) showed remarkable anti-inflammatory activity and could reduce the mRNA expression of proinflammatory cytokines IL-1β, IL-6, TNF-α, and iNOS induced by LPS. Most notably, compounds 1– 4 were formed biogenetically from 6– 7 via the key intramolecular [4+2] cycloaddition, while compound 5 could be constructed biogenetically from 8 through the intramolecular [4+2] cycloaddition. All the above eight polyketides are proposed to originate from a C ₁₀ and a C ₆ fatty acid.

Keywords

Marine-derived fungus / Eutypella sp. F0219 / Polyketides / Polycyclic macrolides / [4+2] cycloaddition

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