Epicorazine B

A unified synthetic strategy directed towards mycotoxins belonging to the thiodiketopiperazine family is reported. The building blocks for a number of natural products--including exserohilone, gliotoxin, the epicoccins, the epicorazines, rostratin A and aranotin--have been synthesised stereoselectively from a common precursor. This key intermediate was constructed through an efficient and highly diastereoselective [2+2] cycloaddition between a ketene and an enecarbamate derived from L-pyroglutamic acid. The annelation of the second ring was accomplished through ring-closing metathesis and enol ether-olefin ring-closing metathesis to provide both cis- and trans-annelated azabicyclic cyclohexenones, as well as an annelated seven-membered cyclic enol ether. A Pd-catalysed elimination of allyl acetate gave rise to the cyclohexadienol structure of gliotoxin. Dimerisation of one building block to afford the diketopiperazine core was demonstrated.

In the course of an ethnobotanical study on fungi used in Yemeni ethnomedicine the fungus Podaxis pistillaris (Podaxales, Podaxaceae, Basidiomycetes) was found to exhibit antibacterial activity against Staphylococcus aureus, Micrococcus flavus, Bacillus subtilis, Proteus mirabilis, Serratia marcescens and Escherichia coli. In the culture medium of P. pistillaris three epidithiodiketopiperazines were identified by activity-guided isolation. Based on spectral data (NMR, ESI-MS and DCI-MS) their identity was established as epicorazine A (1), epicorazine B (2) and epicorazine C (3, antibiotic F 3822), which have not been reported as constituents of P. pistillaris previously. It is assumed that the identified compounds contribute to the antibacterial activity of the extract.

The antimicrobial activities of seven Epicoccum purpurascens strains isolated either from evergreen oak leaves (Quercus ilex) collected over a period of one year, or from the atmosphere were compared in vitro. Two strains sporulated and conspicuously inhibited the growth of Staphylococcus aureus and Trichophyton mentagrophytes. Thin-layer chromatographic studies showed the existence of some compounds, such as flavipin, which were common to all the strains. Epicorazine B was present in the extracts of only the two most active strains.