Dihydroxylation of aromatic compounds

While chemical methods for the controlled dihydroxylation of aromatic compounds are still missing, Rieske nonheme iron dioxygenases, are capable of regio- and stereoselective cis-dihydroxylation of aromatic compounds [149, 150]. The mechanism of this demanding oxidation where both atoms of dioxygen are incorporated into the cii-diol product has been carefully investigated [3d, 150a, 151]. 

In Scheme 1.2 one possible retrosynthetic analysis of the unnatural enantiomer of shikimic acid, a major biosynthetic precursor of aromatic a-amino acids, is sketched. Because cis dihydroxylations can be performed with high diastereoselectiv-ity and yield, this step might be placed at the end of a synthesis, what leads to a cyclohexadienoic acid derivative as an intermediate. Chemoselective dihydroxylation of this compound should be possible, because the double bond to be oxidized is less strongly deactivated than the double bond directly bound to the (electron-withdrawing) carboxyl group. 

A variety of biochemical pathways are known which may lead to reactive quinoid derivatives. They include dihydroxylation of aromatic or heterocyclic compounds and epoxide formation and hydrolysis to -diphenolic compounds (Booth and Boyland 1957) o- and p-hydroxylations of phenols or arylamines (In-SCOE et al. 1965 Miller et al. 1960 Booth and Boyland 1957) and rearrangement of -hydroxyarylamines to o-aminophenols (Miller and Miller 1960). It now appears that aromatic hydroxylations proceed via highly reactive arene oxides, i.e., compounds in which a formal aromatic double bond has undergone epoxidation. Depending on the compound, arene oxides may give rise to other electrophilic reactive species, including quinoid structures, but react as such readily with nucleophiles and thus provide a basis for understanding covalent attachment of aromatic hydrocarbon derivatives to protein and nucleic acids (Jerina and Daly 1974). 

Co(III)/Co(I) redox-mediated electroreduction [18]. Oxidative transformations, e.g., oxidation of side chain of aromatic compounds, 1,2-dihydroxylation of olefins, and oxidation of alcohols and amines, are attained by electrooxidation with CAN, Ct203, Mn(S04)2, TiC104, OSO4, RUO2, and so on as a mediator [19]. 

Arene.. dioxygenases catalyze reactions other than dihydroxylation of aromatics. For example, toluene dioxygenase catalyzes monooxygenation of indene and indan to 1-indenol and 1-indanol, respectively [382], oxidation of polyhalogenated compounds such as trichloroethylene [eq. (24)] [363, 388-390], and stereoselective sulfoxidation of sulfides [391, 392]. 

The uncatalysed p-coumaric acid oxidation led to the formation of intermediates (not shown here) almost similar to those of the catalysed reaction, without formation of dihydroxylated aromatic compounds, such as 3,4- dihydroxybenzaldehyde. This result shows that the catalyst may promote the hydroxylation of aromatic ring by enhancing the formation of hydroxyl radicals in the reaction mixture. 

Monoterpenes in wines (principal structures are reported in Fig. 4.1) are mostly mono- and dihydroxylated alcohols and ethers (Strauss et al., 1986 Rapp et al., 1986 Versini et al., 1991 Winterhalter et al., 1998 Bitteur et al., 1990 Guth, 1995 Farina et al., 2005). These compounds, associated with the floral aroma of aromatic grapes, such as Muscat and Malvasie, Gewiirztraminer, and Riesling, are important variety markers (Rapp et al., 1978). 

Resorcinol diols represent a new class of aromatic dihydroxylic compounds with the general formula (15.33) ... 

Oxidations/hydroxylations of linactivated saturated carbons (polyunsaturated) fatty acids epoxidation and dihydroxylation of alkenes aromatic compounds (- unsaturated diols) hydroxylated compounds and aldehydes diols (and lactonization) enzyme catalyzed Baeyer-Villiger oxidations organic sulfides (sulfoxidation) Be, Mi, Mp, Po, Ra, CytP450 enzymes, monooxygenases SLO An, Nc, Po Pp (mutant strain), Ce Go, Ps Bp, Go, Ko, Ps, HLADH Ac, Ps, CHO BY, An, Ceq, Mi, Po, CPO, BSA... 

Arene dioxygenases catalyze the first step in the metabolism of unactivated aromatic compounds, yielding cw-dihydrodiol of aromatics. As shown in eq. (22), the reaction requires nicotinamide adenine nucleotide (NADH) and molecular oxygen. Substrate specificity of enzymes is high, and products shown in Fig. 27 are produced by benzene-[351, 352], toluene- [353-356], naphthalene- [357-361], biphenyl- [362-364], benzoate-[365-370], and phthalate-dioxygenases [371-378]. In the cases of benzoate [379], 4-sulphobenzoate [380], and 6>-nitrotoluene [381], catechols are formed via unstable dihydroxylated intermediates as shown in eq. (23)... 

With the synthesis of oseltamivir 106, Hudlicky and coworkers again demonstrated the importance and versatility of dihydroxylated aromatic compounds obtained from toluene dioxygense [162]. Ethylbenzoate 95 is a very good substrate for TOO and the resulting diol product 96 has been exploited for a very effident chemoenzymatic synthesis of Tamifiu 107. This example also utilized the so-called "plane of latent symmetry" concept [163]. By proper considerations of symmetry, both enantiomers may become available from a single isomer generated by bio-catalytic means (Scheme 9.30). Oseltamivir 106 contains such a latent symmetry axis through the and atoms, which was used for a flexible synthetic route. In... 

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