ABSTRACT
Enantiopure ß-hydroxy sulfoxides and catechol sulfoxides were obtained, by chemoenzymatic synthesis, involving dioxygenase-catalysed benzylic hydroxylation or arene cis-dihydroxylation and cis-diol dehydrogenase-catalysed dehydrogenation. Absolute configurations of chiral hydroxy sulfoxides were determined by X-ray crystallography, ECD spectroscopy and stereochemical correlation. The application of a new range of ß-hydroxy sulfoxides as chiral ligands was examined.
Subject(s)
Dioxygenases/metabolism , Sulfoxides/chemistry , Sulfoxides/metabolism , Biocatalysis , Crystallography, X-Ray , Hydroxylation , Ligands , Models, Molecular , Molecular Structure , Sulfoxides/chemical synthesisABSTRACT
Enantiopure cis-dihydrodiol bacterial metabolites of substituted benzene substrates were used as precursors, in a chemoenzymatic synthesis of the corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene oxide intermediates. A rapid total racemization of the substituted benzene 2,3-oxides was found to have occurred, via their oxepine valence tautomers, in accord with predictions and theoretical calculations. Reduction of a substituted arene oxide to yield a racemic arene hydrate was observed. Arene hydrates have also been synthesised, in enantiopure form, from the corresponding dihydroarene oxide or trans-bromoacetate precursors. Biotransformation of one arene hydrate enantiomer resulted in a toluene-dioxygenase catalysed cis-dihydroxylation to yield a benzene cis-triol metabolite.
Subject(s)
Benzene/chemistry , Oxides/chemistry , Water/chemistry , Catalysis , Molecular Structure , Oxides/chemical synthesis , StereoisomerismABSTRACT
cis-Dihydrodiol metabolites were obtained from dioxygenase-catalysed asymmetric dihydroxylations of five monocyclic (azabiphenyl) and four tricyclic (azaphenanthrene) azaarene substrates. Enantiopurity values and absolute configuration assignments were determined using a combination of stereochemical correlation, X-ray crystallography and spectroscopy methods. The degree of regioselectivity found during cis-dihydroxylation of monocyclic azaarenes (2,3 bond >> 3,4 bond) and of tricyclic azaarenes (bay region > non-bay region bonds) was dependent on the type of dioxygenase used. The cis-dihydrodiol metabolite from an azaarene (3-phenylpyridine) was utilised in the chemoenzymatic synthesis of the corresponding trans-dihydrodiol.
Subject(s)
Aza Compounds/chemistry , Aza Compounds/metabolism , Dioxygenases/metabolism , Benzene/chemistry , Benzene/metabolism , Biocatalysis , Dioxygenases/chemistry , Dioxygenases/genetics , Hydroxylation , Mutagenesis, Site-Directed , Phenanthrenes/chemistry , Phenanthrenes/metabolism , Stereoisomerism , Substrate SpecificityABSTRACT
Dioxygenase-catalysed trioxygenation of alkyl phenyl sulfides and alkyl benzenes yields enantiopure cis-dihydrodiol sulfoxides and triols respectively; naphthalene cis-dihydrodiol dehydrogenase-catalysed aromatisation of these diastereoisomers gives enantiopure catechols of either configuration.
