Epolones:  Novel Sesquiterpene-Tropolones from Fungus OS-F69284 That Induce Erythropoietin in Human Cells

Abstract

In the course of our screening for small molecule modulators of erythropoietin gene expression, two novel sesquiterpene tropolones and pycnidone were isolated from a culture of OS-F69284 (ATCC 74390). Their structures were elucidated by extensive 1H and 13C NMR spectroscopic studies and chemical reactions. These compounds induced erythropoietin gene expression 5-fold at a concentration of 1-1.6 microM.

Chemistry and Biology of Biosynthetic Diels–Alder Reactions

“…Pycnidione (180), [87] eupenifeldin (181), [88] and epolone B (182) [89] are a group of recently isolated fungal metabolites that possess identical tropolone rings attached to a sesquiScheme 35. Biosynthetic studies on culantraramine (167).…”

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

“…Green tea catechin EGCG increases the level of nuclear HIF-1a protein and activates the expression of HIF-1 downstream genes . The structurally related fungal sesquiterpenes pycnidione, epolone A, and epolone B induce erythropoietin expression via HIF-1a activation (Cai et al, 1998;Wanner et al, 2000). In a study of cultured dorsal root ganglia, it was found that neuronal NO induces the HIF-1-dependent expression of erythropoietin in adjacent Schwann cells, and the erythropoietin in turn protects axons of the neurons against neurotoxin-induced degeneration (Keswani et al, 2011).…”

Malettinin E, an antibacterial and antifungal tropolone produced by a marine Cladosporium strain

“…Representative structures of fungi are puberulic acid, puberulonic acid, stipitatic acid and related structures (Corbett et al, 1950;Iwatsuki et al, 2011). More complex known compounds are epolone A or B, pycnidione, eupenifeldin or fusariocin C (Ito et al, 1981;Mayerl et al, 1993;Cai et al, 1998), which structurally share the fused tropolone/dihydropyran ring structure with the malettinins. However, malettinins 1-4 are unique with regard to their linkage of the tropolone/dihydropyran ring to a furan.…”