Ricinodols A–G: new tetracyclic triterpenoids as 11β-HSD1 inhibitors from Ricinodendron heudelotii

Abstract

A search for 11β-HSD1 inhibitors from Ricinodendron heudelotii has afforded seven new tetracyclic triterpenoids ricinodols A–G (1–7), along with three known podocarpane-type diterpenoids (8–10). Ricinodols A (1) and B (2) possess a new carbon skeleton with a novel concurrent rearrangement of Me-19 (10 → 9) and Me-30 (14 → 8). Their structures were elucidated by comprehensive spectroscopic analyses and comparison with reported analogues, while the 24R-configuration of those with a 24-OH group was established by an in situ dimolybdenum CD method. Of these isolates, ricinodol E (5) exhibited the best inhibitory activities against both human and mouse 11β-HSD1 with IC₅₀ values of 0.36 ± 0.26 and 0.84 ± 0.18 μM, respectively.