John J. McCullough

Absolute configurations of the arene oxide, trans-dihydrodiol and cis-dihydeodiol products resulting from metabolism of quinoline at the 5,6-bond

Abstract Trans -6-bromo-5-hydroxy-5,6,7,8-tetrahydroquinoline enantiomers have been resolved via their dibenzoyltartrate salt diastereoisomers. X-ray crystallographic analysis of the (+)-dibenzoyltartrate salt obtained from reaction of (+)-dibenzoyltartaric acid and (−)-trans-6-bromo-5-hydroxy-5,6,7,8-tetrahydro-quinoline, when allied to a stereochemical correlation sequence linking the arene oxide, trans -dihydrodiol and cis -dihydrodiol enantiomers, provides an unequivocal assignment of absolute configuration for these quinoline metabolites.

Arene oxides of quinoline: epoxidation, N-oxidation and N-methylation reactions

trans- 5,6,7,8- Diepoxy-5,6,7,8-tetrahydroquinoline 5, 5,6-epoxy-5,6-dihydroquinoline 1-oxide 3, 7,8-epoxy-7,8-dihydroquinoline 1 -oxide 4 and trans- 5,6,7,8 -diepoxy - 5,6,7,8 -tetrahydroquinoline1-oxide 6 have been formed by oxidation of the corresponding arene oxides of quinoline, 5,6-epoxy5,6-dihydroquinoline 1 and 7,8-epoxy-7,8-dihydroquinoline 2. The cis-diepoxides, cis-5,6,7,8-diepoxy-5,6,7,8-tetrahydroquinoline 8 and cis-5,6,7,8-diepoxy-5,6,7,8-tetrahydroquinoline 1-oxide 9 were both obtained by a stepwise synthesis from 7,8-epoxy-7,8-dihydroquinoline 2via the bromohydrin 7. N-Methylation of 5,6-epoxy-5,6-dihydroquinoline 1 and 7,8-epoxy-7,8-dihydroquinoline 2 with methyl trifIuoromethanesulphonate yielded the corresponding N-methylquinolinium arene oxide salts 10 and 11.

Synthesis of arene oxide and trans-dihydrodiol metabolites of quinoline

Racemic samples of 5,6-epoxy-5,6-dihydroquinoline (2)(quinoline 5,6-oxide) and 7,8-epoxy-7,8-dihydroquinoline (4)(quinoline 7,8-oxide) have been synthesised by two methods from the corresponding dihydroquinoline precursors. trans-5,6-Dihydroquinoline-5,6-diol (3) and trans-7,8-dihydroquinoline-7,8-diol (5) were obtained both by multi-step synthetic routes from the corresponding dihydroquinolines and by the direct base-catalysed hydration of the corresponding arene oxides (2) and (4).