287104-70-5Relevant articles and documents
Site-Directed Mutagenesis Studies on the Toluene Dioxygenase Enzymatic System: Role of Phenylalanine 366, Threonine 365 and Isoleucine 324 in the Chemo-, Regio-, and Stereoselectivity
Vila, María Agustina,Umpiérrez, Diego,Veiga, Nicolás,Seoane, Gustavo,Carrera, Ignacio,Rodríguez Giordano, Sonia
, p. 2149 - 2157 (2017/06/23)
Toluene Dioxygenase (TDO) enzymatic complex has been widely used as a biocatalyst for the regio- and enantioselective preparation of cis-cyclohexadienediols, which are very important starting materials for organic synthesis. However, the lack of regio- and stereodiversity of the dioxygenation process by TDO and related dioxygenases constitutes a clear drawback when planning the use of these diols in synthetic schemes. In this work, we developed three TDO mutants in residues phenylalanine 366, threonine 365 and isoleucine 324, with the aim to alter the chemo-, regio- and stereoselectivity of the biotransformation of arenes. While no changes in the regioselectivity of the process were observed, dramatic variations in the chemo- and enantioselectivity were found for mutants I324F, T365N and F366 V in a substrate-dependent manner. (Figure presented.).
Medium-scale preparation of useful metabolites of aromatic compounds via whole-cell fermentation with recombinant organisms
Endoma, Mary Ann,Bui, Vu P.,Hansen, Jeff,Hudlicky, Tomas
, p. 525 - 532 (2013/09/06)
The whole-cell fermentation of aromatic coumpounds with Escherichia coli JM109 (pDTG601) on a medium scale (10-15L) produces enantiopure cyclohexadienediols. A detailed procedure for the fermentation is described, and yields for several metabolites are provided. A similar procedure using E. coli JM109 (pDTG602) affords catechols. The dienediols are useful for asymmetric synthesis, and several important targets originating from these metabolites are tabulated.
A study of substrate specificity of toluene dioxygenase in processing aromatic compounds containing benzylic and/or remote chiral centers
Bui,Hansen,Stenstrom,Hudlicky,Ribbons
, p. 116 - 124 (2007/10/03)
A series of substituted arenes containing remote chiral centers were screened as substrates for toluene dioxygenase (TDO). The absolute stereochemistry of the new metabolites was determined by chemical and spectroscopic correlation with synthetic standards. There was no evidence for kinetic resolution; enantiomers were indiscriminately processed by the enzyme to diastereomeric pairs, which were separable upon derivatization. Some of these new metabolites are useful as synthons for morphine synthesis. Full experimental details are reported for those new compounds stable to isolation and for derivatives of those that are unstable.
Enantioselective toluene dioxygenase catalysed di- and tri-hydroxylation of monosubstituted benzenes
Boyd, Derek R.,Sharma, Narain D.,Bowers, Nigel I.,Duffy, John,Harrison, John S.,Dalton, Howard
, p. 1345 - 1350 (2007/10/03)
Asymmetric cis-dihydroxylation to yield diols 2A-2G and sequential benzylic monohydroxylation-cis-dihydroxylation to yield triols 4A-4G (trihydroxylation), occurred during biotransformation of a series of monosubstituted alkylbenzene substrates 1A-1G using toluene dioxygenase, a biocatalyst present in Pseudomonas putida UV4. Dioxygenase-catalysed cis-dihydroxylation of the R and S benzylic alcohol enantiomers 3B-3D, 3B′-3D′ gave the corresponding enantiopure triols 4B-4D, 4B′-4D′. Biotransformation of substrates 1J-1L yielded cis-diols 2J-2L and a minor triol metabolite 4A. Benzylic alcohols 3J-3L were postulated as unstable intermediates yielding triol 4A via benzaldehyde 5 and benzyl alcohol 3A intermediates, cis-Dihydroxylation of monosubstituted benzylic substrates containing bulky groups (1H, 1I) or 1,4-dialkyl-substituted benzene substrates (10A-10C) gave the corresponding cis-dihydrodiol metabolites (2H, 2I, 11A-11C) exclusively. The cis-diols 2A-2L, 11A-11C and triols 4A-4F, 4B′-4D′ were stereochemically assigned as single enantiomers of 1S,2R-configuration based on NMR and CD spectroscopy. The absolute configurations of the exocylic chiral centres in the triol bioproducts 4A-4F, 4B′-4D′ were established by stereochemical correlation and aromatisation/hydrogenation to yield the corresponding enantiopure phenolic benzylic alcohols having similar CD spectra.
Toluene dioxygenase-mediated oxidation of aromatic substrates with remote chiral centers
Bui, Vu,Hansen, Trond Vidar,Stenstrom, Yngve,Ribbons, Douglas W.,Hudlicky, Tomas
, p. 1669 - 1672 (2007/10/03)
Several aromatic substrates containing remote chiral centers were subjected to toluene and naphthalene dioxygenase expressed in blocked mutants and recombinant organisms yielding cis-diol metabolites with little or no kinetic resolution. Substrates were t
