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

Nitin S. Nandurkar; Rico Petersen; Katrine Qvortrup; Vitaly V. Komnatnyy; Kennedy M. Taveras; Sebastian T. Le Quement; Robin Frauenlob; Michael Givskov; Thomas E. Nielsen

doi:10.1016/j.tetlet.2011.10.103

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

Nitin S. Nandurkar, Rico Petersen, Katrine Qvortrup, Vitaly V. Komnatnyy, Kennedy M. Taveras, Sebastian T. Le Quement, Robin Frauenlob, Michael Givskov, Thomas E. Nielsen^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

10 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Tetrahedron Letters
Vol/bind	52
Udgave nummer	52
Sider (fra-til)	7121-7124
Antal sider	4
ISSN	0040-4039
DOI	https://doi.org/10.1016/j.tetlet.2011.10.103
Status	Udgivet - 28 dec. 2011

Bibliografisk note

Funding Information:
The Hans Christian Oersted Postdoc Program, Technical University of Denmark (DTU), Carlsberg Foundation, Lundbeck Foundation, Danish Councils for Strategic and Independent Research, and Holm Foundation are gratefully acknowledged for the financial support.

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10.1016/j.tetlet.2011.10.103

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Citationsformater

@article{b108ec35b82145de829d800feac77df2,

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

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

note = "Funding Information: The Hans Christian Oersted Postdoc Program, Technical University of Denmark (DTU), Carlsberg Foundation, Lundbeck Foundation, Danish Councils for Strategic and Independent Research, and Holm Foundation are gratefully acknowledged for the financial support. ",

year = "2011",

month = dec,

day = "28",

doi = "10.1016/j.tetlet.2011.10.103",

language = "English",

volume = "52",

pages = "7121--7124",

journal = "Tetrahedron Letters",

issn = "0040-4039",

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TY - JOUR

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

AU - Nandurkar, Nitin S.

AU - Petersen, Rico

AU - Qvortrup, Katrine

AU - Komnatnyy, Vitaly V.

AU - Taveras, Kennedy M.

AU - Le Quement, Sebastian T.

AU - Frauenlob, Robin

AU - Givskov, Michael

AU - Nielsen, Thomas E.

N1 - Funding Information: The Hans Christian Oersted Postdoc Program, Technical University of Denmark (DTU), Carlsberg Foundation, Lundbeck Foundation, Danish Councils for Strategic and Independent Research, and Holm Foundation are gratefully acknowledged for the financial support.

PY - 2011/12/28

Y1 - 2011/12/28

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 - HDAC inhibitor

KW - Hydroxamic acids

KW - Hydroxylamine

KW - PEGA resin

KW - Solid-phase synthesis

UR - http://www.scopus.com/inward/record.url?scp=82255193897&partnerID=8YFLogxK

U2 - 10.1016/j.tetlet.2011.10.103

DO - 10.1016/j.tetlet.2011.10.103

M3 - Journal article

AN - SCOPUS:82255193897

SN - 0040-4039

VL - 52

SP - 7121

EP - 7124

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 52

ER -