European Journal of Medicinal Chemistry 2003-01-01

A sequential high-yielding large-scale solution-method for synthesis of philanthotoxin analogues.

Petrine Wellendorph, Jerzy W Jaroszewski, Steen Honoré Hansen, Henrik Franzyk

Index: Eur. J. Med. Chem. 38(1) , 117-22, (2003)

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Abstract

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.Copyright 2002 Editions scienctifiques et médicales Elsevier SAS