Eutypetides A−E, structurally intriguing polyketides forming by
Intramolecular [4+2] cycloaddition from the marine-derived fungus
Eutypella sp. F0219
Abstract
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(3H)-one motif, named
eutypetide E (5) were isolated from the ma-rine-derived fungus Eutypella
sp. F0219, together with three new related biosynthetic polyketides
eutypetides F−H (6−8). The abso-lute configurations of 1−5 were
unequivocally determined by single-crystal X-ray diffraction analyses
(Cu Kα), and electronic circular dichroism (ECD) calculations.
Eutypetides G (7) showed remarkable anti-inflammatory activity and could
reduce the mRNA expres-sion of proinflammatory cytokines IL-1β, IL-6,
TNF-α, and iNOS induced by LPS. Most notably, compounds 1, 2, and 5 were
formed bi-ogenetically from 6−8 via the key intramolecular [4+2]
cycloaddition, respectively.