ChemInform Abstract: Enzymatic Dihydroxylation of Aromatics in Enantioselective Synthesis: Expanding Asymmetric Methodology

Hudlický, Tomáš; González, David; Gibson, David T.

doi:10.1002/chin.200007280

Cited by 35 publications

(44 citation statements)

References 9 publications

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“…These are, as already shown for mono-DHDs, quite useful as precursors in synthetic applications due to two different features, the vicinal hydroxy groups and the conjugated diene substructure (Boyd and Sheldrake 1998; Hudlicky et al 1999). Thus, the bis-DHDs may serve as scaffolds for the syntheses of numerous symmetric bicyclic entities.…”

Section: Applications Of Bis-dhdsmentioning

confidence: 76%

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An aryl dioxygenase shows remarkable double dioxygenation capacity for diverse bis-aryl compounds, provided they are carbocyclic

Overwin

González

Méndez

et al. 2016

Appl Microbiol Biotechnol

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CitationAn aryl dioxygenase shows remarkable double dioxygenation capacity for diverse bis-aryl compounds, provided they are carbocyclic. 2016, 100 (18) AbstractThe bacterial dioxygenation of mono-or polycyclic aromatic compounds is an intensely studied field. However, only in a few cases has the repeated dioxygenation of a substrate possessing more than a single aromatic ring been described. We previously characterized the aryl-hydroxylating dioxygenase BphA-B4h, an artificial hybrid of the dioxygenases of the biphenyl degraders Burkholderia xenovorans LB400 and Pseudomonas sp. strain B4-Magdeburg, which contains the active site of the latter enzyme, as an exceptionally powerful enzyme. We now show that this dioxygenase possesses a remarkable capacity for the double dioxygenation of various bicyclic aromatic compounds, provided that they are carbocyclic. Two groups of biphenyl analogues were examined: series A compounds containing one heterocyclic aromatic ring and series B compounds containing two homocyclic aromatic rings. Whereas all of the seven partially heterocyclic biphenyl analogues were solely dioxygenated in the homocyclic ring, four of the six carbocyclic bis-aryls were converted into ortho,meta-hydroxylated bis-dihydrodiols. Potential reasons for failure of heterocyclic dioxygenations are discussed. The obtained bis-dihydrodiols may, as we also show here, be enzymatically re-aromatized to yield the corresponding tetraphenols. This opens a way to a range of new polyphenolic products, a class of compounds known to exert multiple biological activities. Several of the obtained compounds are novel molecules.

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Section: Applications Of Bis-dhdsmentioning

confidence: 76%

“…A large number of reports have been published describing the turnover of primarily aromatic substrates by bacterial ARHDOs (Hudlicky et al 1999;Johnson 2004). Many of these compounds possess more than a single aromatic ring.…”

Section: Direct and Indirect Evidences For Double Dioxygenationsmentioning

confidence: 99%

An aryl dioxygenase shows remarkable double dioxygenation capacity for diverse bis-aryl compounds, provided they are carbocyclic

Overwin

González

Méndez

et al. 2016

Appl Microbiol Biotechnol

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“…This categorization was usually supported by relatively rapid turnover of the respective substrate and by a corresponding clustering upon alignment of the dioxygenase sequences (Chakraborty et al, 2012;Gibson & Parales, 2000;Nam et al, 2001). Several studies have shown, however, that these enzymes can possess a fairly relaxed substrate specificity (Boyd & Bugg, 2006;Hudlicky et al, 1999). To extend these studies, we sought to systematically characterize and compare the abilities of two powerful biphenyl dioxygenases, the biphenyl-2,3 dioxygenase (BphA) enzyme of Burkholderia xenovorans LB400 (Bopp, 1986;Haddock et al, 1993Haddock et al, , 1995Mondello, 1989;Seeger et al, 1995aSeeger et al, , 1999) and a hybrid enzyme, based on a dioxygenase from Pseudomonas sp.…”

Section: Introductionmentioning

confidence: 99%

“…The enzymic dioxygenation of aromatic compounds is also of considerable synthetic interest (Boyd & Sheldrake, 1998;Hudlicky et al, 1999). Generally, de-aromatization reactions are chemically difficult due to the stability of the aromatic system.…”

Section: Introductionmentioning

confidence: 99%

“…The conversion of the aromatic nucleus into a ring possessing vicinal hydroxy groups as well as a conjugated diene substructure ( Fig. 1) yields a dienediol (DD) molecule (often termed a dihydrodiol), which represents a versatile chiral building block, as it is able to undergo a variety of different follow-up reactions (Hudlicky et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Permissivity of the biphenyl-specific aerobic bacterial metabolic pathway towards analogues with various steric requirements

et al. 2015

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It has repeatedly been shown that aryl-hydroxylating dioxygenases do not possess a very high substrate specificity. To gain more insight into this phenomenon, we examined two powerful biphenyl dioxygenases, the well-known wild-type enzyme from Burkholderia xenovorans LB400 (BphA-LB400) and a hybrid enzyme, based on a dioxygenase from Pseudomonas sp. B4-Magdeburg (BphA-B4h), for their abilities to dioxygenate a selection of eight biphenyl analogues in which the second aromatic ring was replaced by aliphatic as well as aliphatic/aromatic moieties, reflecting a variety of steric requirements. Interestingly, both enzymes were able to catalyse transformation of almost all of these compounds. While the products formed were identical, major differences were observed in transformation rates. In most cases, BphA-B4h proved to be a significantly more powerful catalyst than BphA-LB400. NMR characterization of the reaction products showed that the metabolite obtained from biphenylene underwent angular dioxygenation, whereas all other compounds were subject to lateral dioxygenation at ortho and meta carbons. Subsequent growth studies revealed that both dioxygenase source strains were able to utilize several of the biphenyl analogues as sole sources of carbon and energy. Therefore, prototype BphBCD enzymes of the biphenyl degradative pathway were examined for their ability to further catabolize the lateral dioxygenation products. All of the ortho-and meta-hydroxylated compounds were converted to acids, showing that this pathway is quite permissive, enabling catalysis of the turnover of a fairly wide variety of metabolites.

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Biocatalysis: Synthesis of Chiral Intermediates for Drugs

Patel

2008

Biocatalysis and Bioenergy

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ChemInform Abstract: Enzymatic Dihydroxylation of Aromatics in Enantioselective Synthesis: Expanding Asymmetric Methodology

Cited by 35 publications

References 9 publications

An aryl dioxygenase shows remarkable double dioxygenation capacity for diverse bis-aryl compounds, provided they are carbocyclic

An aryl dioxygenase shows remarkable double dioxygenation capacity for diverse bis-aryl compounds, provided they are carbocyclic

Permissivity of the biphenyl-specific aerobic bacterial metabolic pathway towards analogues with various steric requirements

Biocatalysis: Synthesis of Chiral Intermediates for Drugs

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