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

• Published in: Journal of organic chemistry Vol. 64; no. 11; pp. 4005 - 4011
• Main Authors: Boyd, Derek R, Sharma, Narain D, Hempenstall, Francis, Kennedy, Martina A, Malone, John. F, Allen, Christopher C. R, Resnick, Sol M, Gibson, David T
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 28.05.1999; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; OXIDATION; BENZANTHRACENE; BENZOPYRENE; ABSOLUTE-CONFIGURATION; RAT; PSEUDOMONAS-PUTIDA; CIS-1,2-DIHYDRODIOL; BACTERIAL; CHRYSENE; PHENANTHRENE
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo982517n

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 1H 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.