Garcimultiflins A–C, unusual polycyclic polyprenylated acylphloroglucinols from the pericarps of Garcinia multiflora as interleukin-1β and pyroptosis inhibitors

Abstract

Garcimultiflins A–C (1–3), three novel polycyclic polyprenylated acylphloroglucinols (PPAPs), were isolated from the pericarps of Garcinia multiflora. Their structures and absolute configurations were established by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction. All three compounds are ring-opening derivatives of PPAPs with a caged tricyclo[3.3.1.1.^4,8]decane skeleton. Compounds 1 and 2 are characterized by a 7-oxaspiro[4.5]decan-6-one core, compound 2 was the first example of a PPAP characterized by rearomatization and methyl migration, and compound 3 has a (decahydronaphthalen-2-yl)(phenyl)methanone core. A plausible biosynthetic pathway for these new skeleton compounds was proposed. Furthermore, in lipopolysaccharides plus nigericin-induced THP-1 macrophages, compound 2 dose-dependently suppressed the secretion of interleukin-1β and pyroptosis through inhibiting the activation of NLRP3 inflammasome.