Hypaluton A, an Immunosuppressive 3,4-<i>nor</i>-Polycyclic Polyprenylated Acylphloroglucinol from <i>Hypericum patulum</i>

Abstract

Hypaluton A (<b>1</b>), an unprecedented <i>nor</i>-polycyclic polyprenylated acylphloroglucinol (PPAP) bearing a new 8/6 bicyclic architecture, along with a new congener, hypaluton B (<b>2</b>), was obtained from <i>Hypericum patulum</i>. Their structures were confirmed by spectroscopic analyses, quantum-chemical ¹³C NMR calculations, electronic circular dichroism comparisons, and calculations. Hypaluton A is the first PPAP possessing an unparalleled 3,4-<i>nor</i>-bicyclic polyprenylated acylphloroglucinol (BPAP) scaffold, which might be derived from the common [5.3.1]-type-BPAP by losing seven carbons (C-3/4 of the acylphloroglucinol core and the isoprenyl at C-3) <i>via</i> the breakage at C-4-C-5 and C-2-C-3 bonds in the acylphloroglucinol core, together with the benzoyl migration through the hemiketalization/retro-Claisen cascade. More significantly, compound <b>1</b> is also the first discovered [6.3.0]-PPAP, which displayed pronounced inhibitory activity against lipopolysaccharide-induced B lymphocyte proliferation.