Humulane-Type Macrocyclic Sesquiterpenoids From the Endophytic Fungus Penicillium sp. of Carica papaya

Three new humulane-type sesquiterpenoids, penirolide A ( ), penirolide B ( ), and 10-acetyl-phomanoxide ( ), together with three known compounds aurasperone A ( ), pughiinin A ( ), and cyclo(l-Leu-l-Phe) ( ) were isolated from the endophytic fungus sp derived from the leaves of L. Their structures including their absolute configurations were determined based on the analysis of NMR and HRESIMS spectra, NMR chemical shifts, and ECD calculations. Compounds , , , and significantly inhibited glucagon-induced hepatic glucose production, with EC values of 33.3, 36.1, 18.8, and 32.1 μM, respectively. Further study revealed that compounds , , , and inhibited hepatic glucose production by suppression of glucagon-induced cAMP accumulation.