Improved synthesis and purification of methylated amanitins using diazomethane.
We have examined the conditions of methylating alpha-amanitin with diazomethane with the intent of producing 6'-O-methyl-alpha-amanitin (meAMA). Under the appropriate conditions meAMA was afforded as the sole product in nearly quantitative yield. By exceeding the stoichiometries designed for optimal meAMA synthesis, a dimethylated amanitin, 1'-N-, 6'-O-dimethyl-alpha-amanitin (dimeAMA), was also produced. Both products were characterized, following HPLC, by ultraviolet and n.m.r. spectroscopy. Based upon their inhibitory potential against wheat germ RNA polymerase II, apparent dissociation constants of 4.3 nM and 5.4 nM were estimated for meAMA and dimeAMA, respectively.
D000546:Amanitins / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D003978:Diazomethane; D008745:Methylation; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors
D000546:Amanitins; D003978:Diazomethane; D012319:RNA Polymerase II