A convenient procedure for the solid-phase synthesis of hydroxamic acids on PEGA resins

Nitin Subhash Nandurkar; Rico Petersen; Katrine Qvortrup; Vitaly V. Komnatnyy; Kennedy Taveras; Sebastian Thordal Le Quement; Robin Frauenlob; Michael Givskov; Thomas Eiland Nielsen

doi:10.1016/j.tetlet.2011.10.103

A convenient procedure for the solid-phase synthesis of hydroxamic acids on PEGA resins

Nitin Subhash Nandurkar, Rico Petersen, Katrine Qvortrup, Vitaly V. Komnatnyy, Kennedy Taveras, Sebastian Thordal Le Quement, Robin Frauenlob, Michael Givskov, Thomas Eiland Nielsen

Department of Chemistry

University of Copenhagen

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

An efficient method for the solid-phase synthesis of hydroxamic acids is described. The method comprises the nucleophilic displacement of esters immobilized on PEGA resins with hydroxylamine/sodium hydroxide in isopropanol. The hydroxyaminolysis protocol is compatible with a broad range of PEGA-supported peptide and peptidomimetic esters. The methodology was found to be compatible with two new strategies for the synthesis of solid-supported lactams and diketopiperazines, respectively, both relying on the high inter- and intramolecular reactivity of cyclic N-acyliminium ions with electron-rich aromatics and heteroaromatics, ultimately affording hydroxamic acid derivatives in high purities.

Original language	English
Journal	Tetrahedron Letters
Volume	52
Issue number	52
Pages (from-to)	7121-7124
ISSN	0040-4039
DOIs	https://doi.org/10.1016/j.tetlet.2011.10.103
Publication status	Published - 2011

Keywords

Hydroxylamine
PEGA resin
Solid-phase synthesis
HDAC inhibitor
Hydroxamic acids

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title = "A convenient procedure for the solid-phase synthesis of hydroxamic acids on PEGA resins",

abstract = "An efficient method for the solid-phase synthesis of hydroxamic acids is described. The method comprises the nucleophilic displacement of esters immobilized on PEGA resins with hydroxylamine/sodium hydroxide in isopropanol. The hydroxyaminolysis protocol is compatible with a broad range of PEGA-supported peptide and peptidomimetic esters. The methodology was found to be compatible with two new strategies for the synthesis of solid-supported lactams and diketopiperazines, respectively, both relying on the high inter- and intramolecular reactivity of cyclic N-acyliminium ions with electron-rich aromatics and heteroaromatics, ultimately affording hydroxamic acid derivatives in high purities.",

keywords = "Hydroxylamine, PEGA resin, Solid-phase synthesis, HDAC inhibitor, Hydroxamic acids",

author = "Nandurkar, {Nitin Subhash} and Rico Petersen and Katrine Qvortrup and Komnatnyy, {Vitaly V.} and Kennedy Taveras and {Le Quement}, {Sebastian Thordal} and Robin Frauenlob and Michael Givskov and Nielsen, {Thomas Eiland}",

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T1 - A convenient procedure for the solid-phase synthesis of hydroxamic acids on PEGA resins

AU - Nandurkar, Nitin Subhash

AU - Petersen, Rico

AU - Qvortrup, Katrine

AU - Komnatnyy, Vitaly V.

AU - Taveras, Kennedy

AU - Le Quement, Sebastian Thordal

AU - Frauenlob, Robin

AU - Givskov, Michael

AU - Nielsen, Thomas Eiland

PY - 2011

Y1 - 2011

N2 - An efficient method for the solid-phase synthesis of hydroxamic acids is described. The method comprises the nucleophilic displacement of esters immobilized on PEGA resins with hydroxylamine/sodium hydroxide in isopropanol. The hydroxyaminolysis protocol is compatible with a broad range of PEGA-supported peptide and peptidomimetic esters. The methodology was found to be compatible with two new strategies for the synthesis of solid-supported lactams and diketopiperazines, respectively, both relying on the high inter- and intramolecular reactivity of cyclic N-acyliminium ions with electron-rich aromatics and heteroaromatics, ultimately affording hydroxamic acid derivatives in high purities.

AB - An efficient method for the solid-phase synthesis of hydroxamic acids is described. The method comprises the nucleophilic displacement of esters immobilized on PEGA resins with hydroxylamine/sodium hydroxide in isopropanol. The hydroxyaminolysis protocol is compatible with a broad range of PEGA-supported peptide and peptidomimetic esters. The methodology was found to be compatible with two new strategies for the synthesis of solid-supported lactams and diketopiperazines, respectively, both relying on the high inter- and intramolecular reactivity of cyclic N-acyliminium ions with electron-rich aromatics and heteroaromatics, ultimately affording hydroxamic acid derivatives in high purities.

KW - Hydroxylamine

KW - PEGA resin

KW - Solid-phase synthesis

KW - HDAC inhibitor

KW - Hydroxamic acids

U2 - 10.1016/j.tetlet.2011.10.103

DO - 10.1016/j.tetlet.2011.10.103

M3 - Journal article

SN - 0040-4039

VL - 52

SP - 7121

EP - 7124

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 52

ER -

A convenient procedure for the solid-phase synthesis of hydroxamic acids on PEGA resins

Abstract

Keywords

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