Synthesis of analogues of amaninamide, an amatoxin from the white Amanita virosa mushroom.
Analogs of amaninamide, due to the absence of a 6-hydroxy group in the tryptophan moiety, are more easily accessible by synthesis than derivatives of alpha-amanitin. Syntheses of bicyclic octapeptide thioethers 1f-1m have been carried out starting from linear Hpi-S-trityl-octapeptides (3), cyclization by intramolecular 2'-indolylthioether formation yielding monocyclic peptides (2) and final cyclization by DCCI. One of the bicyclic thioethers was oxidized to yield the corresponding chromatographically separated (R)- and (S)-sulfoxides, respectively. The products were characterized by RF-values, u.v. and CD spectra as well as by mass (FAB) spectroscopy. The widely differing inhibitory activities on RNA polymerase II (or B) from calf thymus are listed.
C.N.R. Institute of Pharmaceutical Chemistry, University La Sapienza, Rome, Italy.
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G
Zanotti
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C
Möhringer
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T
Wieland
D000546:Amanitins / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008970:Molecular Weight; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000201:enzymology
D000546:Amanitins; D007202:Indicators and Reagents; D012319:RNA Polymerase II