bis-cis-Dihydrodiols: A New Class of Metabolites Resulting from Biphenyl Dioxygenase-Catalyzed Sequential Asymmetric cis-Dihydroxylation of Polycyclic Arenes and Heteroarenes

The biphenyl dioxygenase-catalyzed asymmetric mono - cis -dihydroxylation of the tetracyclic arenes chrysene 1A, benzo[ c ]phenanthridine 1B, and benzo[ b ]naphtho[2,1- d ]thiophene 1C, has been observed to occur exclusively at the bay or pseudo-bay region using the bacterium Sphingomonas yanoikuyae B8/36. The mono - cis -dihydrodiol derivatives 2A and 2C, obtained from chrysene 1A by oxidation at the 3,4-bond (2A) and benzo[ b ]naphtho[2,1-d]thiophene 1C by oxidation at the 1,2-bond (2C), respectively, have been observed to undergo a further dioxygenase-catalyzed asymmetric cis -dihydroxylation at a second bay or pseudo-bay region bond to yield the corresponding bis - cis -dihydrodiols ( cis -tetraols) 4A and 4C, the first members of a new class of microbial metabolites in the polycyclic arene series. The enantiopurities and absolute configurations of the new mono - cis -dihydrodiols 2B, 2C, and 3B were determined by 1 H NMR analyses of the corresponding ( R )- and ( S )-2-(1-methoxyethyl)benzeneboronate (MPBA) ester derivatives. The structure and absolute configurations of the bis - cis -dihydrodiols 4A and 4C were unambiguously determined by spectral analyses, stereochemical correlations, and, for the metabolite 4C, X-ray crystallographic analysis of the bis -acetonide derivative 7C . These results illustrate the marked preference of biphenyl dioxygenase for the cis -di- and tetra-hydroxylations of polycyclic arenes, at the more hindered bay or pseudo-bay regions, by exclusive addition from the same (si:si) face, to yield single enantiomers containing two and four chiral centers.