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.
Zanotti
G
G
C.N.R. Institute of Pharmaceutical Chemistry, University La Sapienza, Rome, Italy.
Möhringer
C
C
Wieland
T
T
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