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

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

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

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

30 Citations (Scopus)

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.

Original language	English
Journal	European Journal of Medicinal Chemistry
Volume	38
Issue number	1
Pages (from-to)	117-22
Number of pages	6
ISSN	0223-5234
Publication status	Published - 2003

Keywords

Chromatography, Liquid
Combinatorial Chemistry Techniques
Electrophoresis, Capillary
Magnetic Resonance Spectroscopy
Models, Chemical
Phenols
Polyamines
Silica Gel
Silicon Dioxide
Solutions
Tyrosine

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title = "A sequential high-yielding large-scale solution-method for synthesis of philanthotoxin analogues",

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.",

keywords = "Chromatography, Liquid, Combinatorial Chemistry Techniques, Electrophoresis, Capillary, Magnetic Resonance Spectroscopy, Models, Chemical, Phenols, Polyamines, Silica Gel, Silicon Dioxide, Solutions, Tyrosine",

author = "Petrine Wellendorph and Jaroszewski, {Jerzy W} and Hansen, {Steen Honor{\'e}} and Henrik Franzyk",

year = "2003",

language = "English",

volume = "38",

pages = "117--22",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson",

number = "1",

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TY - JOUR

T1 - A sequential high-yielding large-scale solution-method for synthesis of philanthotoxin analogues

AU - Wellendorph, Petrine

AU - Jaroszewski, Jerzy W

AU - Hansen, Steen Honoré

AU - Franzyk, Henrik

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - Chromatography, Liquid

KW - Combinatorial Chemistry Techniques

KW - Electrophoresis, Capillary

KW - Magnetic Resonance Spectroscopy

KW - Models, Chemical

KW - Phenols

KW - Polyamines

KW - Silica Gel

KW - Silicon Dioxide

KW - Solutions

KW - Tyrosine

M3 - Journal article

C2 - 12593922

SN - 0223-5234

VL - 38

SP - 117

EP - 122

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 1

ER -

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

Abstract

Keywords

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