A sequential high-yielding large-scale solution-method for synthesis of philanthotoxin analogues.
A general, improved procedure for rapid synthesis of philanthotoxin analogues, a pharmacologically important class of polyamine conjugates, is described. The solution-phase procedure is illustrated by gram-scale synthesis of philanthotoxins PhTX-343 and PhTX-12. Selectively protected polyamines are coupled to N(alpha)-Fmoc-protected amino acid pentafluorophenyl esters. After removal of the N(alpha)-Fmoc group, the amine is coupled with carboxylic acid pentafluorophenyl esters. Deprotection followed by a rapid and efficient purification by vacuum liquid chromatography on octadecylsilyl silica (RP-18 phase) gave the philanthotoxin analogues in 74-78% overall yield.
Wellendorph
Petrine
P
Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Jaroszewski
Jerzy W
JW
Hansen
Steen Honoré
SH
Franzyk
Henrik
H
D002853:Chromatography, Liquid / Q000379:methods; D020650:Combinatorial Chemistry Techniques; D019075:Electrophoresis, Capillary; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010636:Phenols / Q000138:chemical synthesis* / Q000302:isolation & purification; D011073:Polyamines / Q000138:chemical synthesis* / Q000302:isolation & purification; D058428:Silica Gel; D012822:Silicon Dioxide; D012996:Solutions; D014443:Tyrosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000302:isolation & purification
D010636:Phenols; D011073:Polyamines; D012996:Solutions; C405122:phTX 12; C074003:philanthotoxin 343; D014443:Tyrosine; D058428:Silica Gel; D012822:Silicon Dioxide