Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides.

Molecular docking studies of quinoline and 2-chloroquinoline substrates at the active site of toluene dioxygenase (TDO), were conducted using Autodock Vina, to identify novel edge-to-face interactions and to rationalize the observed stereoselective cis-dihydroxylation of carbocyclic rings and formation of isolable cis-dihydrodiol metabolites. These in silico docking results of quinoline and pyridine substrates, with TDO, also provided support for the postulated cis-dihydroxylation of electron-deficient pyridyl rings, to give transient cis-dihydrodiol intermediates and the derived hydroxyquinolines. 2-Chloroquinoline cis-dihydrodiol metabolites were used as precursors in the chemoenzymatic synthesis of enantiopure arene oxide and arene dioxide derivatives of quinoline, in the context of its possible mammalian metabolism and carcinogenicity.

Synthesis, structure and stereochemistry of quinoline alkaloids from Choisya ternata.

A range of seventeen quinoline alkaloids, involving several types of oxidations during their biosynthetic pathways, have been isolated from leaves of Choisya ternata. In addition to the nine known quinoline alkaloids, eight new members of the furoquinoline family, derived mainly from prenylation at C-5 (including two novel hydroperoxides), have been identified. The absolute configurations and enantiopurity values of all chiral quinoline alkaloids have been determined. One of the isolated alkaloids, 7-isopentenyloxy-gamma-fagarine, has been used as a precursor for the chemical asymmetric synthesis of the enantiopure alkaloids: evoxine, anhydroevoxine and evodine. The possible roles of oxygenase and other oxygen-atom-transfer enzymes, in the biosynthetic pathways of the C. ternata alkaloids, have been discussed.

cis-Dihydrodiol, arene oxide and phenol metabolites of dictamnine: key intermediates in the biodegradation and biosynthesis of furoquinoline alkaloids.

Biotransformation of the parent furoquinoline alkaloid dictamnine and its 4-chlorofuroquinoline precursor, using the B8/36 bacterial mutant strain of Sphingomonas yanoikuyae, yielded, via biphenyl dioxygenase-catalysed dihydroxylation, the first isolable alkaloid cis-dihydrodiol metabolites; these metabolites were used in the chemoenzymatic synthesis of postulated arene oxide and phenol intermediates, and a range of derived furoquinoline alkaloids.

Absolute configuration assignment and enantiopurity determination of chiral alkaloids and coumarins derived from O- and C-prenyl epoxides.

A combination method of ozonolysis and chiral stationary phase (CSP)-GC-MS analysis has been developed to determine the enantiopurity values and absolute configurations of a range of alkaloid and coumarin hemiterpenoids derived from C- and O-prenyl epoxides.