Work

Hyperimonates A and B, a pair of unprecedented polyprenylated acylphloroglucinols from Hypericum monogynum: Structural elucidation, total synthesis, and lipid-lowering activity

Year: 2025

Type: article

Abstract: Hyperimonates A ( 1 ) and B ( 2 ), two minor polycyclic polyprenylated acylphloroglucinols (PPAPs) with unprecedented hexahydro-1 H -cyclopenta[ c ]furan-1-one and 2-oxabicyclo[2.2.1]heptane ring system were isolated from Hypericum monogynum . To obtain adequate materials for biological research, the asymmetric total syntheses of 1 and 2 were completed from commercially available geraniol via a bioinspired strategy that features an Au(I)-catalyzed carbometallic cascade cyclization and a Mn(III)/Cu(II) mediated oxidative radical cyclization as vital steps. Biological study implied that compound 1 showed excellent lipid-lowering activity in vitro via inhibiting two signaling pathways, Notch and PPAR, further verified by non-alcoholic fatty liver disease (NAFLD) zebrafish model. These findings provide a new structural template for the treatment of NAFLD and asymmetric synthetic approaches could also facilitate further evaluation for drug development. Hyperimonates A ( 1 ) and B ( 2 ), two unprecedented polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated and synthesized. Both compounds exhibited excellent lipid lowering activity in vitro and in vivo .

Source: Acta Pharmaceutica Sinica B

DOI: 10.1016/j.apsb.2025.10.008