Biosynthesis arene oxides

VI. Arene Oxides as Intermediates in the Biosynthesis of Natural Products... 

Hydroxylation of aromatic rings is a very common and an important step in the biosynthesis of natural products.181,182 Arene oxides were suggested as intermediates in the biosynthesis of natural products as early as in 1967.183 However, not all hydroxylations proceed through arene oxides. A number of instances have been documented,184 as in the case of cinnamic and benzoic acids, where ortho and para hydroxylations take place by the involvement of an NIH shift (arene oxides). 

Involvement of arene oxides has been suggested in the biosynthesis of a number of natural products like 340 from 338 through intermediate 339.185 Formation of semiperivirol, totarol, ferruginol, and podocarpic acid from... 

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... 

Aranotins and Sirodesmin.—ctc/o-(l Phenylalanyl-L-seryl) is an efficient and intact precursor for gliotoxin (114) (cf. Vol. 10, p. 27). Bisdethiobis(methylthio)-acetylaranotin (115) is related to gliotoxin in the biosynthesis of this metabolite, it is believed that ring-opening of an arene oxide las (116)1 occurs, followed by further epoxidation and cyclization, as in the biosynthesis of gliotoxin (114).2... 

Intramolecular nucleophilic attack of an amine group on an arene oxide has been proposed to account for the biosynthesis of a range of epipolythiopiperazine-diones (e.g., gliotoxin, bis-dithiobis-(methylthio)dehydrogliotoxin, spirodesmins, etc.)- With the amine-substituted arene oxides 50 and 55 (Figure 3), synthe-... 

Figure 12 Mercapturic acid biosynthesis from a naphthaiene 1,2-oxide. Oniy one of fhe isomers resuifing from reacfion of GSH wifh fhe arene oxide is shown. (1) giufafhione S-transferase, (2) y-giufamyifranspepfidase, (3) cysfeinyigiycinase acfivify (dipepfidases), and (4) A/-acefyifransferase.

Arene oxides are important intermediates in the biosynthesis of biochemically important phenols such as tyrosine and serotonin. 

Ganem B, Holbert G W 1977 Arene oxides in biosynthesis. On the origin of crotepoxide, senepox-ide, and pipoxide. Bioorg Chem 6 393-396... 

Two reactions dominate the chemistry of arene oxides the first which has been discussed above is their facile conversion to phenols and the second is their valence bond tautomerism to oxepins. Circumstantial evidence for the role of an aromatic epoxide type of intermediate (119) in the biosynthesis is provided by the location of two oxepin structural units in the related metabolite arantoin (113). The origin of these rings has been plausibly attributed to valence bond tautomerism of an L-phenylalanine epoxide Figure 4.18) and some experimental data to support this suggestion has been obtained by Brannon, Mabe, Molloy and Day . These workers showed that [ Hs]-L-phenylalanine was readily incorporated into acetylarantoin in Aspergillus terreus and contributed seven (or fourteen) hydrogen atoms to the molecule. In this case, in... 

There is strong evidence that the biosynthesis of salicylic acid 75 from benzoic acid 72 by the fungus Phellinus tremulae runs via an arene oxide 73 [36] (Fig. 12). The mechanism is principally the same as that for naphthalene and quinoline, but in this case the rearrangement product 2-carbomethoxyoxepin 74 was also found in the supernatant of the fungus. 

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