1100595-75-2Relevant articles and documents
Semi-Rational Engineering of Toluene Dioxygenase from Pseudomonas putida F1 towards Oxyfunctionalization of Bicyclic Aromatics
Wissner, Julian L.,Schelle, Jona T.,Escobedo-Hinojosa, Wendy,Vogel, Andreas,Hauer, Bernhard
, p. 4905 - 4914 (2021)
Toluene dioxygenase (TDO) from Pseudomonas putida F1 was engineered towards the oxyfunctionalization of bicyclic substrates. Single and double mutant libraries addressing 27 different positions, located at the active site and entrance channel were generated. In total, 176 different variants were tested employing the substrates naphthalene, 1,2,3,4-tetrahydroquinoline, and 2-phenylpyridine. Introduced mutations in positions M220, A223 and F366, exhibited major influences in terms of product formation, chemo-, regio- and enantioselectivity. By semi-rational evolution, we lighted up the TDO capability to convert bulkier substrates than its natural substrate, at unprecedented reported conversions. Thus, the most active TDO variants were applied to biocatalytic oxyfunctionalizations of 1,2,3,4-tetrahydroquinoline, and 2-phenylpyridine, enabling the production of substantial amounts of (+)-(R)-1,2,3,4-tetrahydroquinoline-4-ol (71% isolated yield, 94% ee) and (+)-(1S,2R)-3-(pyridin-2-yl)cyclohexa-3,5-diene-1,2-diol (60% isolated yield, 98% ee), respectively. Here, we provide a set of novel TDO-based biocatalysts useful for the preparation of oxyfunctionalized bicyclic scaffolds, which are valuable to perform downstream synthetic processes. (Figure presented.).
Regioselectivity and stereoselectivity of dioxygenase catalysed cis-dihydroxylation of mono- and tri-cyclic azaarene substrates
Boyd, Derek R.,Sharma, Narain D.,Coen, Gerard P.,Hempenstall, Francis,Ljubez, Vera,Malone, John F.,Allen, Christopher C. R.,Hamilton, John T. G.
experimental part, p. 3957 - 3966 (2009/06/27)
cis-Dihydrodiol metabolites were obtained from dioxygenase-catalysed asymmetric dihydroxylations of five monocyclic (azabiphenyl) and four tricyclic (azaphenanthrene) azaarene substrates. Enantiopurity values and absolute configuration assignments were determined using a combination of stereochemical correlation, X-ray crystallography and spectroscopy methods. The degree of regioselectivity found during cis-dihydroxylation of monocyclic azaarenes (2,3 bond >> 3,4 bond) and of tricyclic azaarenes (bay region > non-bay region bonds) was dependent on the type of dioxygenase used. The cis-dihydrodiol metabolite from an azaarene (3-phenylpyridine) was utilised in the chemoenzymatic synthesis of the corresponding trans-dihydrodiol. The 2008 Royal Society of Chemistry.
