(±)-Applanatumines B–D: novel dimeric meroterpenoids from Ganoderma applanatum as inhibitors of JAK3

Abstract

Applanatumines B–D (1–3), three pairs of dimeric meroterpenoid enantiomers featuring the presence of a 6-oxo-4,4a,5,5a,6,8,8a,8b-octahydrofuro[3′,4′:4,5]cyclopenta[1,2-b]pyran-3-carbaldehyde structure core, were isolated from the fruiting bodies of Ganoderma applanatum. Their structures and absolute configurations were assigned by using spectroscopic methods and ECD calculations. Biological evaluation found that all the compounds are JAK3 inhibitors. In addition, the enantiomers of 1 are active towards DDR1 with IC₅₀ values of 8.2 ± 0.8 μM and 6.9 ± 0.8 μM. Finally, a plausible biogenic pathway for compounds 1–3 was proposed.