Page 27 - Tyrosine-Based Bioconjugations - Jorick Bruins
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General Introduction
  Scheme 6. Crosslinking of HA-tagged eDHFR by tyrosine polymerization.
1.3.3. Iminoquinones
Similar to regular quinones, ortho-iminoquinones (28) (from now on referred to as iminoquinones) can be generated from aminophenols (29) upon oxidation with NaIO4 or K3Fe(CN)6,106, 107 or by photoactivation of azidophenols (30) (Scheme 7).108 Based on their ability to selectively react with nucleophilic nitrogen atoms like the N-terminus of a protein or the amine functionality of anilines,106, 109 iminoquinone derivatives have found useful applications in bioconjugation chemistry.110 After Michael addition of an N-terminal amino acid or aniline residue, tautomerization to (32) occurs and a second oxidation takes place to yield (33) in presence of oxidant (Scheme 7) or (34) if N-terminal proline was the utilized as nucleophile.110 It was observed that proline was most reactive and yielded the highest conversion among all amino acid residues.109 Francis et al. also observed that NaIO4 was a more potent oxidant than K3Fe(CN)6, but also gave rise to multiple products whereas K3Fe(CN)6 only yielded a single product.107 Furthermore, when photoactivation of azidophenols was performed to obtain iminoquinones, coupling with the N-terminus of proteins was not observed due a much higher reaction rate of aniline addition and a general lack of N-terminal coupling at pH 6.0.109
Besides nucleophilic addition, iminoquinones are also able to undergo (4+2) cycloaddition with acrylamides, leading to morpholine-type structures (31).111 Due to the electron-poor character of the acrylamide double bond, cycloaddition in this case proceeds via the regular hetero-Diels– Alder HOMO-LUMO interaction of alkene with the oxygen and nitrogen atom.
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