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A Unified Strategy Targeting the Thiodiketopiperazine Mycotoxins Exserohilone, Gliotoxin, the Epicoccins, the Epicorazines, Rostratin A and Aranotin
Author(s) -
Gross Ulrike,
Nieger Martin,
Bräse Stefan
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201001169
Subject(s) - gliotoxin , mycotoxin , biology , microbiology and biotechnology , aspergillus fumigatus
Abstract 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.