C/s-dihydrodiols

Figure 7.6a Stereochemical control with benzene c/s-dihydrodiols.

J Chem Soc Chem Commun 17 954-955 Ballard DGH, Moran KT, Shirley IM (1984) Conducting polymers. EP 122079 Ballard DGH, Courtis A, Shirley IM, Taylor SC (1988) Synthesis of polyphenylene from a cis-dihydrocatechol biologically produced monomer. Macromolecules 21 294-304 Ballard DGH, Blacker AJ, Woodley JM, Taylor SC (1994) Polyphenylenes from biosynthetic cis-dihydroxycyclohexadiene. In Mobley DP (ed) Plastics from microbes microbial synthesis of polymers and polymer precursors. Htmser, New York, pp 139-168 Berresheim AJ, Muller M, Klaus M (1999) Polyphenylene nanostructures. Chem Rev 99 1747-1785 Boyd DR, Bugg TDH (2006) Arene c/s-dihydrodiol formtition from biology to application. Org Biomol Chem 4 181-192... 

As mentioned in Section 32.2, arene c/s-dihydrodiols of type 2 undergo facile dehydration reactions (usually catalyzed by Brpnsted acid) that rearomatize the ring and give phenols 166 (Scheme 32.21). Such dehydrations are far more rapid than for the corresponding dehydration of arene f rans-dihydrodiols (which may be accessed by hydrolysis of the epoxide ring in arene oxides... 

DEWAR STRUCTURES KEKULE STRUCTURES c/s-Benzene dihydrodiol dehydrogenase,... 

Figure 2. Intermediates in the aerobic bacterial metabolism of benzene. (I) c/s-benzene dihydrodiol, (II) catechol, (III) 2-hydroxymuconic semialdehyde, (IV) cis, cis- muconic acid.

In general, K-region arene oxides behave rather like aliphatic epoxides and thus readily undergo hydration reactions, whereas benzene oxides and non-K-region arene oxides form dihydrodiols much more reluctantly. Kinetic studies of the mechanism of solvolysis of phenanthrene 9,10-oxide 2 have been carried out in several laboratories.Below pH 7 the hydrolysis reaction was acid-catalyzed and the products included the trans- and c/s-9,10-dihydrodiols along with a preponderance of 9-phenanthrol, while above pH 7 the reaction proceeded via the spontaneous mechanism ( o) mainly the frans-dihydrodiol. 

The c/s-dihydroxylation reaction catalyzed by these dioxygenases is typically highly enantioselective (often >98% ee) and, as a result, has proven particularly useful as a source of chiral synthetic intermediates (2,4). Chiral cis-dihydrodiols have been made available commercially and a practical laboratory procedure for the oxidation of chlorobenzene to IS, 2S)-3-chlorocyclohexa-3,5-diene-l,2-c diol by a mutant strain of Pseudomonas putida has been published (6). Transformation with whole cells can be achieved either by mutant strains that lack the second enzyme in the aromatic catabolic pathway, cw-dihydrodiol dehydrogenase (E.C. 1.3.1.19), or by recombinant strains expressing the cloned dioxygenase. This biocatalytic process is scalable, and has been used to synthesize polymer precursors such as 3-hydroxyphenylacetylene, an intermediate in the production of acetylene-terminated resins (7). A synthesis of polyphenylene was developed by ICI whereby ftie product of enzymatic benzene dioxygenation, c/s-cyclohexa-3,5-diene-1,2-diol, was acetylated and polymerized as shown in Scheme 2 (8). 

FIGURE 8.7 Examples of chemical syntheses based on cyclohexadiene cis dihydrodiols (a) pinitol, (b) condnramine A, (c) (-)-laminitol, and (d) conduritol analogs. (From Neilson, A.H. and Allard, A.-S. The Handbook of Environmental Chemistry, Springer, 1998. With permission.)... 

Studies using either molecular oxygen-18 or oxygen-18 water indicated that the 4R,5R-dihydrodiol is derived by water attack at the C-4 position of the metabolically formed 4,5-epoxide intermediate (15.21), These results established that 4S,5R-epoxide is formed as the metabolic precursor of the 4R,5R-dihydrodiol. Hydration studies of the optically pure BaP 4,5-epoxide enantiomers indicated that the 4S,5R-epoxide is hydrated exclusively at the S-center (C-4 position) whereas 85% of the 4R,5S-epoxide is hydrated at the S-center (C-5 position) (22 and Figure 4). 

The 9,10-dihydrodiol of 3-MC (24a) was synthesized from 9-hy-droxy-3-MC by Method IV (86). Oxidation of this phenol with Fremy s salt in the presence of Adogen 464, a quaternary ammonium phase transfer catalyst, furnished 3-MC 9,10-dione. Reduction of the qui-none with NaBH -C gave pure 24a in good yield. Treatment of 24a with m-chloroperbenzoic acid was monitored by HPLC in order to optimize the yield of the anti diol epoxide (25 ) and minimize its decomposition. 

Figure 22.16. Structures of the dihydrodiol epoxides of several polycyclic aromatic hydrocarbons. (A) Benzo[a]pyrene-fnms-7,8-dihydrodiol-9,10-epoxide (BPDE) (B) benz[a]anthracene-frara-8,9-dihydrodiol-10,11-epoxide (BADE) (C) benzo[fe]fluoranthene-fnms-9,10-dihydrodiol-ll, 12-epoxide (BFDE) (D) chrysene-fnms-l,2-dihydrodiol-3,4-epoxide (CDE) and (E)dibenzo[a,/]pyrene-fra ,s-ll,12-dihydrodiol-13,14-epoxide (DBPDE). Only one enantiomer for each dihydrodiol epoxide is shown.

Chang RJ, Levin W, Wood AW, Kumar S, Yagi H, Jerina DM, Lehr RE, Conney AH (1984) Tumorigenicity of dihydrodiols and diol-epoxides of benz[c] acridines in newborn mice. Cancer Res 44 5161-5164... 

T., Malone, J.F., McGregor, S. and Allen, C.C.R. (2005) Dioxygenase-catalyzed dihydroxylation of arene cis-dihydrodiols and acetonide derivatives a new approach to the synthesis of enantio-pure tetraoxygenated bioproducts from arenes. Chemical Communications, 4934-4936. 

Biological activation of polycyclic-hydrocarbon carcinogens proceeds through dihydrodiols and diol epoxides and such pathways are clearly possible for aza-aromatic compounds. To assist in investigating the existence of such routes, a range of dihydrodiols and diol epoxides of benz[c]acridine and benz[a]acridine (R.E. Lehr and S. Kumar, J. org. Chem., 1981, 367 ... 

Sutherland, J.B., P.P. Fu, S.K. Yang, L.S. von Tungelnm, R.P. Casillas, S.A. Crow, and C.E. Cerniglia. 1993. Enantiomeric composition of the frans-dihydrodiols produced from phenanthrene by fungi. Appl. Environ. Microbiol. 59 2145-2149. 

Cheng, S.C., Hilton, B.D., Roman, J.M., and Dipple, A. (1989) DNA adducts from carcinogenic and noncarcinogenic enantiomers of benzo[a]pyrene dihydrodiol epoxide. Chem. Res. Toxicol., 2, 334-340. 

Pfeiffer E., Hildebrand A.A., Becker C., Schnattinger C., Baumann S., Rapp An., Goesmann H., Syldatk C., Metzler M. Identification of an aliphatic epoxide and the corresponding dihydrodiol as novel congeners ofzearalenone in cultures of Fusariumgraminearum. Journal of Agricultural and Food Chemistry, 58 12055-12062 (2010). 

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