Synthesis and Reactivity of a Bis-Strained Alkyne Derived from 1,1′-Biphenyl-2,2′,6,6′-tetrol

TY - JOUR

T1 - Synthesis and Reactivity of a Bis-Strained Alkyne Derived from 1,1′-Biphenyl-2,2′,6,6′-tetrol

AU - Knighton, Richard C.

AU - Sharma, Krishna

AU - Robertson, Naomi S.

AU - Spring, David R.

AU - Wills, Martin

N1 - Funding Information: We acknowledge support from the Engineering and Physical Sciences Research Council (EP/M006670/1; R.C.K. and EP/ P020291/1; D.R.S. & N.S.R.) and The Royal Society (Wolfson Research Merit Award to DRS). Crystallographic data were collected using instruments purchased through support from Advantage West Midlands (AWM) and the European Regional Development Fund (ERDF) or from the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 637313). K.S. would like to thank Trinity College, Cambridge Trust, Cambridge Nehru Trust, and the Cambridge Philosophical Society for providing fellowships. We are grateful for the Polymer Characterization RTP (Warwick) and Dan Lester for providing access to the GPC instrument described in the General Experimental Section. Part of this work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. Publisher Copyright: © 2019 American Chemical Society.

PY - 2019/1/29

Y1 - 2019/1/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85060779245&partnerID=8YFLogxK

U2 - 10.1021/acsomega.8b03634

DO - 10.1021/acsomega.8b03634

M3 - Article

AN - SCOPUS:85060779245

SN - 2470-1343

VL - 4

SP - 2160

EP - 2167

JO - ACS Omega

JF - ACS Omega

IS - 1

ER -