Arene cis -Diol Dehydrogenase-Catalysed Regio- and Stereoselective Oxidation of Arene-, Cycloalkane- and Cycloalkene- cis -diols to Yield Catechols and Chiral α-Ketols (original) (raw)
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Advanced Synthesis & Catalysis, 2007
A series of cis-dihydrodiol metabolites, available from the bacterial dioxygenase-catalysed oxidation of monosubstituted benzene substrates using Pseudomonas putida UV4 , have been converted to the corresponding catechols using both a heterogeneous catalyst (Pd/C) and a naphthalene cis-diol dehydrogenase enzyme present in whole cells of the recombinant strain Escherichia coli DH5a(pUC129: nar B). A comparative study of the merits of both routes to 3-substituted catechols has been carried out and the two methods have been found to be complementary. A similarity in mechanism for catechol formation under both enzymatic and chemoenzymatic conditions, involving regioselective oxidation of the hydroxyl group at C-1, has been found using deuterium labelled toluene cis-dihydrodiols. The potential, of combining a biocatalytic step (dioxygenase-catalysed cis-dihydroxylation) with a chemocatalytic step (Pd/C-catalysed dehydrogenation), into a one-pot route to catechols, from the parent substituted benzene substrates, has been realised.
Green Chemistry, 2000
Several catechols have been prepared directly from aromatic precursors by treatment with the recombinant organism Escherichia coli JM109 (pDTG602), which expresses both toluene dioxygenase (TDO) and dihydrocatechol dehydrogenase (DHCD), the first two enzymes in the natural biodegradation pathway of aromatics by Pseudomonas species. The yields and the ease of preparation of these compounds are compared with traditional chemical methods. For three of the products, the E value and EMY (effective mass yield, is defined as the percentage of the mass of desired product relative to the mass of all non-benign materials in its synthesis, see ref. 9) are calculated and compared with those obtained by traditional methods to indicate the green component of the preparation. Potential for direct introduction of the catechol unit to various natural product synthons is discussed.
Biochemistry, 2018
Laboratory evolution of alcohol dehydrogenase produced enzyme variants with improved turnover numbers with a vicinal 1,2-diol and its corresponding hydroxyketone. Crystal structure and transient kinetics analysis aids in rationalizing the new functions of these variants. E nzymes can provide effective alternative routes as catalysts in synthetic chemistry, 1−4 and the "green-ness" of biocatalysis can contribute to a more sustainable manufacturing of chemicals. An important chemical transformation in synthetic chemistry is the oxidation of secondary alcohols and the reduction of the corresponding ketones. Partial oxidation of 1,2-substituted (vicinal) diols can produce the corresponding αhydroxy ketones (acyloins) that are attractive building blocks for chiral auxiliaries, natural products, and pharmaceuticals. 5−7 Enzyme-catalyzed production of acyloins has been demonstrated to be feasible using monooxygenases or alcohol dehydrogenases. 8−10 Alcohol dehydrogenase A (ADH-A) from the bacterium Rhodococcus ruber DSM 44541 is an interesting candidate biocatalyst of redox reactions. ADH-A is unusually tolerant toward organic solvents, is highly regio-and enantioselective, and displays activity with a wide range of alcohols and ketones, including aryl-substituted vicinal diols. 11−14 The catalyzed oxidation of 1,2-diols by the wild-type enzyme is, however, relatively inefficient; the k cat /K M for oxidation of (R)-2 (Chart 1) into the corresponding hydroxy ketone 4 is approximately 3000-fold lower than that for the oxidation of (S)-1 into acetophenone (3) (Table 1). ADH-A follows an ordered sequential bi-bi mechanism with a low degree of accumulation of the ternary complex at the steady state. 14 The rate-limiting step for the turnover of preferred substrates such as (S)-1 is NADH release (k 5 in Scheme 1, Table 2). It is noteworthy that in a strictly ordered mechanism the NADH off rate is expected to be independent of the alcohol substrate (or ketone product) because this step involves only the binary enzyme−nucleotide complex. ADH-A displays a k cat with (R)-2 of 0.73 s −1 , which is 70-fold lower than the NADH release rate (Table 2). Assuming that oxidation of (R)-2 still obeys an ordered mechanism, the lower turnover rate is presumably due to nonproductive substrate binding, 15 where the alcohol is bound in the ternary
Journal of Molecular Catalysis B: Enzymatic, 2008
ABSTRACT Alcohol and carbonyl groups are highly recurrent groups in organic compounds. Their redox equilibrium is often used by chemists to prepare several compounds. Carbonyl reactivity is often used to synthesize more complex structures; in contrast, alcohols are more usually found in the final products because their coordinative ability is fundamental both in biology and in chemistry. Dehydrogenase activities are an interesting alternative to chemical redox reactants because they are often chemo-, regio-, and stereo-selective. We prepared and used an E. coli recombinant strain expressing the naphthalene dihydrodiol dehydrogenase from Pseudomonas fluorescens N3. This biocatalyst showed satisfactory substrate recognition and good reactivity. It can transform primary and secondary alcohols and 1,2-diols. Besides, the geometry recognition is also significant. Finally, we will discuss some unexpected results that we obtained when using 1,2-diols.
BMC Biotechnology, 2010
Background Substituted catechols are important precursors for large-scale synthesis of pharmaceuticals and other industrial products. Most of the reported chemical synthesis methods are expensive and insufficient at industrial level. However, biological processes for production of substituted catechols could be highly selective and suitable for industrial purposes. Results We have optimized a process for bio-catalytic production of 3-substituted catechols viz. 3-nitrocatechol (3-NC) and 3-methylcatechol (3-MC) at pilot scale. Amongst the screened strains, two strains viz. Pseudomonas putida strain (F1) and recombinant Escherichia coli expression clone (pDTG602) harboring first two genes of toluene degradation pathway were found to accumulate 3-NC and 3-MC respectively. Various parameters such as amount of nutrients, pH, temperature, substrate concentration, aeration, inoculums size, culture volume, toxicity of substrate and product, down stream extraction, single step and two-step b...
Microbial Stereoselective One-Step Conversion of Diols to Chiral Lactones in Yeast Cultures
Catalysts, 2015
It has been shown that whole cells of different strains of yeast catalyze stereoselective oxidation of meso diols to the corresponding chiral lactones. Among screening-scale experiments, Candida pelliculosa ZP22 was selected as the most effective biocatalyst for the oxidation of monocyclic diols 3a-b with respect to the ratio of high conversion to stereoselectivity. This strain was used in the preparative oxidation, affording enantiomerically-enriched isomers of lactones: (+)-(3aR,7aS)-cis-hexahydro-1(3H)-isobenzofuranone (2a) and (+)-(3aS,4,7,7aR)-cis-tetrahydro-1(3H)-isobenzofuranone (2b). Scaling up the culture growth, as well as biotransformation conditions has been successfully accomplished. Among more bulky substrates, bicyclic diol 3d was totally converted into enantiomerically-pure exo-bridged (+)-(3aR,4S,7R,7aS)-cis-tetrahydro-4,7methanoisobenzofuran-1(3H)-one (2d) by Yarrovia lipolytica AR71. Microbial oxidation of diol 3f by Candida sake AM908 and Rhodotorula rubra AM4 afforded optically-pure cis-3butylhexahydro-1(3H)-isobenzofuranone (2f), however with low conversion.
Advanced Synthesis & Catalysis, 2009
Regio-and stereoselective reductions of several diketones to afford enantiopure hydroxy ketones or diols were accomplished using isolated alcohol dehydrogenases (ADHs). Results could be rationalised taking into account different (promiscuous) substrate-binding modes in the active site of the enzyme. Furthermore, interesting natural cyclic diketones were also reduced with high regio-and stereoselectivity. Some of the 1,2-and 1,3-diketones used in this study were reduced by employing a low excess of the hydrogen donor (2-propanol) due to the quasi-irreversibility of these ADH-catalysed processes. Thus, using lower quantities of co-substrate, scale-up could be easily achieved.
ChemistryOpen, 2018
A chemo‐ and biocatalytic cascade approach was applied for the stereoselective synthesis of hydroxy ketones and the corresponding 1,3‐diols. A new class of tridentate N,N,O ligands was used with copper(II) complexes for the asymmetric β‐borylation of α,β‐unsaturated compounds. The complex containing ligand L5 emerged as the best performer, and it gave the organoborane derivatives with good ee values. The corresponding keto–alcohol compounds were then bioreduced by yeasts. The biotransformation set up with Rhodotorula rubra allowed (R)‐keto–alcohols and (S,S)‐diols to be obtained with up to 99 % ee and up to 99 % de in favor of the anti enantiomers.