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 t he tetracyclic arenes chrysene 1A, benzo[c]phenanthridine 1B, and benzo[b]n aphtho[2,1-d]thiophene 1C, has been observed to occur exclusively at the ba y or pseudo-bay region using the bacterium Sphingomonas yanoikuyae B8/36. T he 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 o xidation 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-dihydrodio ls (cis-tetraols) 4A and 4C, the first members of a new class of microbial metabolites in the polycyclic arene series. The enantiopurities and absolut e configurations of the new mono-cis-dihydrodiols 2B, 2C, and 3B were deter mined by H-1 NMR analyses of the corresponding (R)- and (S)-2-(1-methoxyeth yl)benzeneboronate (MPBA) ester derivatives. The structure and absolute con figurations of the bis-cis-dihydrodiols 4A and 4C were unambiguously determ ined by spectral analyses, stereochemical correlations, and, for the metabo lite 4C, X-ray crystallographic analysis of the bis-acetonide derivative 7C . These results illustrate the marked preference of biphenyl dioxygenase fo r the cis-di- and tetra-hydroxylations of polycyclic arenes, at the more hi ndered bay or pseudo-bay regions, by exclusive addition from the same (si:s i) face, to yield single enantiomers containing two and four chiral centers .