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

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