A unified strategy targeting the thiodiketopiperazine mycotoxins exserohilone, gliotoxin, the epicoccins, the epicorazines, rostratin a and aranotin

Article abstract of DOI:10.1002/chem.201001169

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 sevenmembered 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.