Biomimetic formation of 2-tropolones by dioxygenase-catalysed ring expansion of substituted 2,4-cyclohexadienones.
Substituted 2-tropolone natural products are found in plants and fungi. Their biosynthesis is thought to occur by ring expansion from a cyclohexadienone precursor, but this reaction has not previously been demonstrated experimentally. Treatment of 6-hydroxy-6-hydroxymethylcyclohexa-2,4-dienone with the non-haem iron(II)-dependent extradiol catechol dioxygenase MhpB from Escherichia coli results in the formation of the 2-tropolone ring-expansion product through a pinacol-type rearrangement. Three further substituted cyclohexa-2,4-dienone analogues were prepared, and treatment of each analogue was found to give the substituted 2-tropolone ring-expansion product. This ring expansion could also be effected nonenzymatically by treatment with 1,4,7-triazacyclononane and FeCl(2). This is a novel transformation for non-haem iron-dependent enzymes, and this is the first experimental demonstration of the proposed ring-expansion reaction in tropolone biosynthesis.
Xin
Meite
M
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
Bugg
Timothy D H
TD
D000935:Antifungal Agents / Q000737:chemistry*; D055162:Biocatalysis; D040761:Biomimetic Materials / Q000737:chemistry*; D053138:Cyclohexenes / Q000737:chemistry*; D049308:Dioxygenases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D005296:Ferrous Compounds / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D014334:Tropolone / Q000737:chemistry*
D000935:Antifungal Agents; D053138:Cyclohexenes; D005296:Ferrous Compounds; D006571:Heterocyclic Compounds; C507608:cyclohexadienone; C075712:1,4,7-triazacyclononane; D014334:Tropolone; D049308:Dioxygenases; C083582:3-carboxyethylcatechol 2,3-dioxygenase; C029451:ferrous chloride