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A new bio-compatible pH cleavable linker for solid-phase synthesis of a squalamine analogue

A new bio-compatible pH cleavable linker for solid-phase synthesis of a squalamine analogue
A new bio-compatible pH cleavable linker for solid-phase synthesis of a squalamine analogue
Linkers that can be cleaved directly within the biological assay offer some advantages over traditional linkers in the range of direct screening applications that the associated libraries can be utilised for. The 1,6-elimination process is an efficient method of cleaning compounds from substituted 4-hydroxymethyl phenols, although giving rise to quinone methide by-products. Here, we report on a linker that uses an in-built amine 'activator' to cleave a phenoxy ester and hence to activate the linker to 1,6-elimination. An analogue of the antibacterial agent squalamine was synthesised and released using this linker strategy.
solid-phase, synthesis, linker, squalamine protected peptide-fragments, organic-synthesis, combinatorialchemistry, resin, libraries
0040-4039
6211-6214
Chitkul, B.
8f090116-13b1-4ccb-b596-322316652109
Atrash, B.
8ff54d4e-de52-4d47-a136-f7c233963bac
Bradley, M.
078a34d6-96c4-4ce1-9aa1-454d9ee0030d
Chitkul, B.
8f090116-13b1-4ccb-b596-322316652109
Atrash, B.
8ff54d4e-de52-4d47-a136-f7c233963bac
Bradley, M.
078a34d6-96c4-4ce1-9aa1-454d9ee0030d

Chitkul, B., Atrash, B. and Bradley, M. (2001) A new bio-compatible pH cleavable linker for solid-phase synthesis of a squalamine analogue. Tetrahedron Letters, 42 (35), 6211-6214. (doi:10.1016/S0040-4039(01)01217-5).

Record type: Article

Abstract

Linkers that can be cleaved directly within the biological assay offer some advantages over traditional linkers in the range of direct screening applications that the associated libraries can be utilised for. The 1,6-elimination process is an efficient method of cleaning compounds from substituted 4-hydroxymethyl phenols, although giving rise to quinone methide by-products. Here, we report on a linker that uses an in-built amine 'activator' to cleave a phenoxy ester and hence to activate the linker to 1,6-elimination. An analogue of the antibacterial agent squalamine was synthesised and released using this linker strategy.

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More information

Published date: 27 August 2001
Keywords: solid-phase, synthesis, linker, squalamine protected peptide-fragments, organic-synthesis, combinatorialchemistry, resin, libraries

Identifiers

Local EPrints ID: 19449
URI: http://eprints.soton.ac.uk/id/eprint/19449
ISSN: 0040-4039
PURE UUID: 00986b2c-bbe1-407f-b06c-688f96d2d9b2

Catalogue record

Date deposited: 14 Feb 2006
Last modified: 15 Mar 2024 06:16

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Contributors

Author: B. Chitkul
Author: B. Atrash
Author: M. Bradley

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