Oxidative Cleavage of Aromatic Rings

Perhaps the most drastic modification which can happen to an aromatic ring is ring cleavage brought about by oxidative enzymes called dioxygenases (see page 27). These enzymes typically use catechol (1,2-dihydroxy) or quinol (1,4-dihydroxy) substrates, require molecular oxygen and Fe2+ cofactors, and incorporate both the oxygen atoms into the ring-cleaved product. In the case of catechols, cleavage may be between or adjacent to the two hydroxyls, giving products containing aldehyde and/or carboxylic acid functionalities (Figure 3.43). These groups are then able to react with other substituents in the molecule creating compounds in which the characteristic acetate-derived features are probably no longer apparent. Shikimate-derived aromatic rings can suffer similar oxidative cleavage reactions.

Patulin is an excellent example of an acetate-derived structure synthesized from an aromatic substrate via oxidative cleavage and subsequent modifications (Figure 3.44). Patulin is a potent carcinogen produced by Penicillium patulum, a common contaminant on apples. If mould-infected apples find their way into food products, e.g.

OH cleavage between ^ hydroxyls

Cco2h

diacid cleavage adjacent to hydroxyls ___

ohoh OH

aldehyde-acid

hydroxylation at decarboxylation facilitated oxidation activated position by ortho hydroxyl

SEnz

CO2H OH

6-methylsalicylic acid hydroxylation at decarboxylation facilitated oxidation activated position by ortho hydroxyl

m-cresol

m-hydroxybenzyl alcohol oxidative cleavage |

gentisyl alcohol

m-cresol neopatulin to patulin conversion involves change of functionality in hemiacetal ring via reduction and oxidation

m-hydroxybenzyl alcohol oxidative cleavage |

gentisyl alcohol of 1,4-quinol

O OH patulin

O OH patulin

h3c-co2h

"oh O

formation of lactone and O cyclic hemiacetal

OH OH Ha O ascladiol neopatulin

O OH

O OH

6-methylsalicylic acid

6-methylsalicylic acid

O OH patulin

OH gentisaldehyde

phyllostine

O OH patulin

OH gentisaldehyde

phyllostine

Figure 3.44

apple juice, fruit pies, etc, then these products may contain unacceptable and dangerous levels of pat-ulin. Such food materials are routinely screened for patulin content, with a tolerance level set at 50 |ig kg-1. Patulin is derived from acetate via 6-methylsalicylic acid (Figure 3.26). Decarboxylation and hydroxylation reactions then lead to genti-syl alcohol (Figure 3.44), which may suffer oxida-tive cleavage as shown. Cleavage of the aromatic ring would generate aldehyde and carboxylic acid functions. By rotating the molecule around the carbon - carbon single bond as shown, it is easy to see that neopatulin can result by formation of hemi-acetal and lactone groups. The reversal of functionality in the hemiacetal ring to produce patulin is achieved by reduction and oxidation reactions involving aldehyde and alcohol components of the hemiacetal. The sequence shown in Figure 3.44 has been deliberately simplified to rationalize the oxidative cleavage. The true sequence involves gentisaldehyde and the epoxyquinone phyllostine as intermediates between gentisyl alcohol and neopatulin.

Penicillic acid (Figure 3.45), another micro-bially produced food contaminant with carcinogenic properties, is synthesized by cultures of Penicillium cyclopium and P. baarnense, and also features oxidative ring fission of an aromatic compound. This time orsellinic acid (Figure 3.25) is a precursor, and ring fission appears to proceed via a quinone, which is the result of decarboxylation, oxidation, and methylation reactions. Figure 3.45 also represents an over-simplistic rationalization of the ring fission process.

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Responses

  • pansy took-took
    How to oxidative cleave a ring?
    8 years ago
  • Lea
    What is aromatic ring oxidation?
    8 years ago
  • Rory
    How to convert orsellinic acid to penicillic acid?
    8 years ago
  • Angelika
    What is ring cleavage?
    3 months ago

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