Oxidative cyclisation of N,N-dialkylcatechol amines to heterocyclic betaines via o-quinones: synthetic, pulse radiolytic and enzyme studies

Clews, John; Cooksey, Christopher J.; Garratt, Peter J.; Land, Edward J.; Ramsden, Christopher A.; Riley, Patrick A.

doi:10.1039/b006860h

Cited by 27 publications

(22 citation statements)

References 28 publications

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“…[27] Calculations of the UV absorption of compound III, which point to a maximum at around 250 nm, support this hypothesis. Therefore, the increase observed at around 250 nm in Figure 1 is suggestive of the formation of the spiro intermediate III.…”

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confidence: 50%

“…[24] In the course of their investigations into melanogenesis, Ramsden and colleagues also published studies on the formation of several homologues of cyclo-DOPA. [25][26][27] This pathway shown in Scheme 1 led us to postulate a biosynthesis of the anachelin chromophore. We propose that the final steps of anachelin biosynthesis start from the precursor A, containing a C-terminal Tyr residue, which is attached to peptide and polyketide fragments (labeled peptide; see Scheme 2).…”

Section: Introductionmentioning

confidence: 98%

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Mechanistic Studies on the Tyrosinase‐Catalyzed Formation of the Anachelin Chromophore

Gademann

2005

ChemBioChem

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The complex secondary metabolite anachelin, isolated from the freshwater cyanobacterium Anabaena cylindrica, is believed to act as siderophore, facilitating iron uptake. Its structure is characterized by a fascinating blend of polyketide, peptide, and alkaloid fragments. In particular, the tetrahydroquinolinium-derived chromophore is unique among natural products, and its biosynthesis is unknown. We propose a hypothesis for the biogenesis of the anachelin chromophore starting from a C-terminally bound L-Tyr residue. It is proposed that this amino acid is reductively aminated, methylated, and hydroxylated. Oxidation of this catechol diamine substrate by a tyrosinase would lead to an o-quinone, which would react by intramolecular aza-annulation and tautomerization to give the anachelin chromophore. In order to evaluate this hypothesis, a model substrate related to the proposed biogenetic precursor was prepared. It was shown that the enzyme tyrosinase is able to transform this substrate into an anachelin chromophore derivative, which corroborates the biogenetic hypothesis. In order to gain further insight into the mechanism of this transformation, we performed spectrophotometric reaction monitoring, allowing the formation of the expected product to be observed. In addition, a rise in absorption at around 250 nm might be due to the presence of a spiro five-membered ring intermediate resulting from an alternative 1,4-addition to the o-quinone. Lastly, we were able to show that the action of tyrosinase on this substrate follows Michaelis-Menten kinetics (k(cat)=123 s(-1) and K(m)=8.66 mM). Interestingly, the catalytic efficiency is decreased only by a factor of 30 relative to the natural substrate L-DOPA.

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supporting

confidence: 50%

Section: Introductionmentioning

confidence: 98%

Mechanistic Studies on the Tyrosinase‐Catalyzed Formation of the Anachelin Chromophore

Gademann

2005

ChemBioChem

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“…21,22 In contrast to tyramine 14 (R ) H), which is oxidized with an oxygen uptake stoichiometry of 1.0 O 2 per mol of substrate after an initial lag period, the N,N-dialkyltyramines 14 remained unoxidized upon prolonged exposure to native tyrosinase. However, addition of a catalytic amount of dopa or use of preactivated tyrosinase This result demonstrates the essential role of redox exchange for autoactivation of tyrosinase and, by inference, the general participation of this mode of reaction in eumelanin formation.…”

Section: 3-dihydro-1h-indolium-5-olate Formation and Tyrosinase Actmentioning

confidence: 97%

Tyrosinase Autoactivation and the Chemistry of ortho-Quinone Amines

2003

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Tyrosinase oxidizes tyrosine to dopaquinone, which undergoes nonenzymatic reactions leading to precursors of melanin pigments. Cyclization of dopaquinone gives cyclodopa, which participates in redox exchange with dopaquinone to give the eumelanin precursor dopachrome plus dopa. The indirect formation of the catechol (dopa) from the phenol (tyrosine) leads to unusual enzyme kinetics. Using a combination of enzyme oximetry, pulse radiolysis, and chemical oxidation, the study of structurally modified dopaquinones provides firm evidence of nonenzymatic catechol formation during tyrosinase oxidation of phenols and reveals significant differences in their modes of reaction.

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“…30,31 It is clear that if quinonequinomethane rearrangement is to be used preparatively then an aqueous solvent is highly desirable.…”

Section: Discussionmentioning

confidence: 99%

Studies of para-quinomethane formation during the tyrosinase-catalyzed oxidation of 4-alkylcatechols

Land¹,

Ramsden²,

Riley³

et al. 2008

Arkivoc

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UV-Vis spectroscopy, hplc-mass spectrometry and deuterium-labeling studies demonstrate that 4-alkyl-ortho-quinones cleanly rearrange to the isomeric 2-hydroxy-para-quinomethanes over a period of 10-20 minutes in aqueous buffer. These ortho-quinones are much more stable in organic solvents (CD 3 OH, CDCl 3 ). Studies of the rate of rearrangement and of the introduction of pre-formed para-quinomethane to enzyme solution demonstrate that the quinomethanes, formed as secondary products, do not contribute to the inactivation of tyrosinase.

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Oxidative cyclisation of N,N-dialkylcatechol amines to heterocyclic betaines via o-quinones: synthetic, pulse radiolytic and enzyme studies

Cited by 27 publications

References 28 publications

Mechanistic Studies on the Tyrosinase‐Catalyzed Formation of the Anachelin Chromophore

Mechanistic Studies on the Tyrosinase‐Catalyzed Formation of the Anachelin Chromophore

Tyrosinase Autoactivation and the Chemistry of ortho-Quinone Amines

Studies of para-quinomethane formation during the tyrosinase-catalyzed oxidation of 4-alkylcatechols

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