Arenes microbial oxidation

T. Hudlicky, H. Luna, G. Barbieri, and L. D. Kwart, Enantioselective synthesis through microbial oxidation of arenes. 

Microbial oxidation of arenes is a feasible process. An example is the conversion of benzene to cylohexa-3,5-diene-1,2-diol (14, R = H) by the bacterium Pseudomonas putida P. putida). The process is stereoselective and with substituted benzenes (14, R h) a single enantiomer is produced (Scheme 11.7). Such compounds are useful starting materials for natural product synthesis. 

Hudlicky, T., H. Luna, G. Barbieri, and L.D. Kwart. 1988. Enantioselective synthesis through microbial oxidation of arenes. 1. Efficient preparation of terpene and prostanoid synthons. /. Am. Chem. Soc. 110 4735-4741... 

Benzene and other arenes can be oxidized to c -l,2-cyclohexadienediol enan-tiospecifically using a mutant of Pseudomonas putida through microbial techniques (equation 188)310. 

The metabolism of 1,4-dichlorobenzene could involve the formation of an arene oxide intermediate, as has been proposed to occur in the oxidative metabolism of many halogenated aromatic hydrocarbons (Jerina and Daly 1974). 1,4-Dichlorobenzene has not been shown to be mutagenic in microbial or mammalian systems, a result that may be viewed as further suggestive evidence that an arene oxide intermediate is not involved in its metabolism. 

Arene oxides and their oxepin tautomers play a role in the biosynthesis of some microbial metabolites, e.g., the sulfur-containing antibiotics gliotoxin (345),188 dehydrogliotoxin (346),189 apoarontin (347),190 aranotin (348),191... 

Johnson, RJV. (2004) Microbial arene oxidations. Organic Reactions, 63,117. 

Microbial ortho- and para-hydroxylation reactions are considered to proceed via the arene oxide, and a phenomenon known as the NIH shift is commonly found to occur (Scheme 16) with di- or poly-substituted substrates. 

For the enantioselective preparations of chiral synthons, the most interesting oxidations are the hydroxylations of unactivated saturated carbons or carbon-carbon double bonds in alkene and arene systems, together with the oxidative transformations of various chemical functions. Of special interest is the enzymatic generation of enantiopure epoxides. This can be achieved by epoxidation of double bonds with cytochrome P450 mono-oxygenases, w-hydroxylases, or biotransformation with whole micro-organisms. Alternative approaches include the microbial reduction of a-haloketones, or the use of haloperoxi-dases and halohydrine epoxidases [128]. The enantioselective hydrolysis of several types of epoxides can be achieved with epoxide hydrolases (a relatively new class of enzymes). These enzymes give access to enantiopure epoxides and chiral diols by enantioselective hydrolysis of racemic epoxides or by stereoselective hydrolysis of meso-epoxides [128,129]. 

A disinfectant, such as a water solution of isopropanol, destroys some but not all organisms. Spores, for example, aren t destroyed by disinfectants. Sterilants are capable of completely eliminating or destroying all forms of microbial life, including spores. Isopropanol is not a sterilant isopropanol Is a good and versatile disinfectant. For chemical sterilization, ethylene oxide is frequently specified. 

Where microbial metabolism occurs, it generally takes the form of a benzene ring-opening reaction, leading to a dicarboxylic acid, or a hydroxy carboxylic acid a catechol may be an intermediate product. A prerequisite appears to be the absence of substituents on the 2 and 3 positions, thus allowing the formation of an arene oxide or a diol as the first stage of the process. This is schematically illustrated in Fig. 3. 

---