A unified strategy targeting the thiodiketopiperazine mycotoxins exserohilone, gliotoxin, the epicoccins, the epicorazines, rostratin A and aranotin.
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.
Gross
Ulrike
U
Institut für Organische Chemie, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
Nieger
Martin
M
Bräse
Stefan
S
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction; D053138:Cyclohexenes / Q000737:chemistry; D005030:Ethylenes / Q000737:chemistry; D005912:Gliotoxin / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D008968:Molecular Conformation; D009183:Mycotoxins / Q000138:chemical synthesis / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry*; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry; D013237:Stereoisomerism
D001688:Biological Products; D053138:Cyclohexenes; D005030:Ethylenes; D007659:Ketones; D009183:Mycotoxins; D010879:Piperazines; C578436:exserohilone; C578437:rostratin A; C052568:cyclohexene; D010165:Palladium; C018283:epicorazine A; D005912:Gliotoxin; C018284:epicorazine B; C002500:aranotin; C008223:ketene; D011761:Pyrrolidonecarboxylic Acid