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Synthesis and reactivity of a bis-strained alkyne derived from 1,1′-Biphenyl-2,2′,6,6′-tetrol

Synthesis and reactivity of a bis-strained alkyne derived from 1,1′-Biphenyl-2,2′,6,6′-tetrol
Synthesis and reactivity of a bis-strained alkyne derived from 1,1′-Biphenyl-2,2′,6,6′-tetrol
The novel "double strained alkyne" 3 has been prepared and evaluated in strain-promoted azide-alkyne cycloaddition reactions with azides. The X-ray crystallographic structure of 3, which was prepared in one step from 1,1′-biphenyl-2,2′,6,6′-tetrol 4, reveals the strained nature of the alkynes. Dialkyne 3 undergoes cycloaddition reactions with a number of azides, giving mixtures of regiosiomeric products in excellent yields. The monoaddition products were not observed or isolated from the reactions, suggesting that the second cycloaddition proceeds at a faster rate than the first, and this is supported by molecular modeling studies. Dialkyne 3 was successfully employed for "peptide stapling" of a p53-based diazido peptide, whereby two azides are bridged to give a product with a stabilized conformation.
2470-1343
2160-2167
Knighton, Richard C.
5a63128e-0ebd-466a-b327-3aee6e85a76d
Sharma, Krishna
7f90398b-ca52-4ae3-952c-ab75d0e76a08
Robertson, Naomi S.
f93698ab-c441-4eb1-bc13-a45d022a92b1
Spring, David R.
5e03dd4b-9d92-4169-aab1-8da241e02a3d
Wills, Martin
4529569b-d977-463d-a99f-fccec46e21a0
Knighton, Richard C.
5a63128e-0ebd-466a-b327-3aee6e85a76d
Sharma, Krishna
7f90398b-ca52-4ae3-952c-ab75d0e76a08
Robertson, Naomi S.
f93698ab-c441-4eb1-bc13-a45d022a92b1
Spring, David R.
5e03dd4b-9d92-4169-aab1-8da241e02a3d
Wills, Martin
4529569b-d977-463d-a99f-fccec46e21a0

Knighton, Richard C., Sharma, Krishna, Robertson, Naomi S., Spring, David R. and Wills, Martin (2019) Synthesis and reactivity of a bis-strained alkyne derived from 1,1′-Biphenyl-2,2′,6,6′-tetrol. ACS Omega, 4 (1), 2160-2167. (doi:10.1021/acsomega.8b03634).

Record type: Article

Abstract

The novel "double strained alkyne" 3 has been prepared and evaluated in strain-promoted azide-alkyne cycloaddition reactions with azides. The X-ray crystallographic structure of 3, which was prepared in one step from 1,1′-biphenyl-2,2′,6,6′-tetrol 4, reveals the strained nature of the alkynes. Dialkyne 3 undergoes cycloaddition reactions with a number of azides, giving mixtures of regiosiomeric products in excellent yields. The monoaddition products were not observed or isolated from the reactions, suggesting that the second cycloaddition proceeds at a faster rate than the first, and this is supported by molecular modeling studies. Dialkyne 3 was successfully employed for "peptide stapling" of a p53-based diazido peptide, whereby two azides are bridged to give a product with a stabilized conformation.

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Accepted/In Press date: 10 January 2019
Published date: 29 January 2019

Identifiers

Local EPrints ID: 482103
URI: http://eprints.soton.ac.uk/id/eprint/482103
ISSN: 2470-1343
PURE UUID: 1a3f1ffd-1740-4ee7-933f-cc9453648dff
ORCID for Richard C. Knighton: ORCID iD orcid.org/0000-0002-0336-3718

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Date deposited: 19 Sep 2023 16:39
Last modified: 18 Mar 2024 04:15

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Contributors

Author: Richard C. Knighton ORCID iD
Author: Krishna Sharma
Author: Naomi S. Robertson
Author: David R. Spring
Author: Martin Wills

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