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Review
. 2018 Apr 3;24(19):4749-4756.
doi: 10.1002/chem.201703919. Epub 2017 Dec 19.

ortho-Quinones and Analogues Thereof: Highly Reactive Intermediates for Fast and Selective Biofunctionalization

Jorick J Bruins  1 , Bauke Albada  1 , Floris van Delft  1
Affiliations
Review

ortho-Quinones and Analogues Thereof: Highly Reactive Intermediates for Fast and Selective Biofunctionalization

Jorick J Bruins et al. Chemistry. .

Abstract

Fast, selective and facile functionalization of biologically relevant molecules is a pursuit of ever-growing importance. A promising approach in this regard employs the high reactivity of quinone and quinone analogues for fast conjugation chemistry by nucleophilic addition or cycloadditions. Combined with in situ generation of these compounds, selective conjugation on proteins and surfaces can be uniquely induced in a time and spatially resolved manner: generation of a quinone can often be achieved by simple addition of an enzyme or stoichiometric amounts of chemoselective oxidant, or by exposure to light. In this Minireview, we discuss the generation and subsequent functionalization of quinones, iminoquinones, and quinone methides. We also discuss practical applications regarding these conjugation strategies.

Keywords: addition reactions; biochemistry; heterocycles; nucleophiles; quinones.

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Figures

Figure 1
Figure 1
Representation of ortho‐quinones, ortho‐iminoquinones, and ortho‐quinone methides.
Scheme 1
Scheme 1
A) Oxidation of tyrosine to its corresponding quinone, followed by a Michael addition of a nucleophilic side‐chain functionality of an amino acid residue R (i.e. Cys, His, or Lys). B) PNA crosslinking by DOPA‐oxidation by NaIO4 and subsequent Michael addition.
Scheme 2
Scheme 2
Crosslinking of HA‐tagged eDHFR by tyrosine polymerization.
Scheme 3
Scheme 3
A) Strain‐promoted oxidation‐controlled cyclooctyne‐1,2‐quinone cycloaddition (SPOCQ) of tert‐butylquinone and BCN; B) SPOCQ performed on tetra‐glycyltyrosine at the C‐terminus of the light chains of antibodies.
Scheme 4
Scheme 4
Generation and subsequent reactions of iminoquinones as reported by Francis et al.
Scheme 5
Scheme 5
Glass surfaces bearing aniline residues and their subsequent modification for DNA‐directed immobilization. ALD=fructose‐bisphosphate aldolase.
Scheme 6
Scheme 6
Selective tissue modification by in situ dephosphorylation and generation of quinone methides.
Scheme 7
Scheme 7
[4+2] cycloaddition with vinyl thioethers and ortho‐quinolinones, for the 2nd generation precursor: R1=biotin or fluorescein piperazine.
See this image and copyright information in PMC

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