ECI Digital Archives

Title

Carboxylation of phenols and asymmetric nucleophile addition across C=C bond

Authors

Kurt Faber, University of Graz, AustriaFollow
S. Payer, Dept. of Chemistry, University of Graz, Austria
K. Plasch, Dept. of Chemistry, University of Graz, Austria
T. Reiter, Dept. of Chemistry, University of Graz, Austria
V. Resch, Dept. of Chemistry, University of Graz, Austria
C. Wuensch, Dept. of Chemistry, University of Graz, Austria
S. M. Glueck, Dept. of Chemistry, University of Graz, Austria
K. Gruber, Inst. of Molecular Biosciences, University of Graz, Austria
G. Steinkellner, Inst. of Molecular Biosciences, University of Graz, Austria
T. Pavkov-Keller, Inst. of Molecular Biosciences, University of Graz, Austria
F. Himo, Dept. of Organic Chemistry, Stockholm University, Sweden
X. Sheng, Dept. of Organic Chemistry, Stockholm University, Sweden

Conference Dates

September 24-28, 2017

Abstract

The regioselective carboxylation of electron-rich (hetero)aromatics employing decarboxylases in the redox-neutral (reverse) carboxylation reaction using bicarbonate or CO2(g) is currently exploited for the biocatalytic synthesis of carboxylic acids.1 Three enzyme classes exert complementary regioselectivities through diverse mechanisms: (i) Whereas the o-carboxylation of phenols (an equivalent to the Kolbe-Schmitt reaction) is mediated by Zn2+-dependent o-benzoic acid (de)carboxylases,2 (ii) the -carboxylation of hydroxystyrenes is catalysed by phenolic/ferulic acid (de)carboxylases acting via a pair of Tyr-Arg residues.3 (iii) Surpringly, these enzymes also exhibit a catalytic promiscuity for the nucleophile addition of H2O,4 NH2-OMe, cyanide and n-Pr-SH across the vinyl C=C bond via a quinone-methide intermediate, which yields the corresponding (S)-configurated adducts in up to 91% e.e.5 (iv) In search of ATP-independent regio-complementary p-benzoic acid (de)carboxylases, we discovered that 3,4-dihydroxybenzoic acid decarboxylase from Enterobacter cloacae6 (DHBDC_Ec) surprisingly depends on prenylated FMN7 as cofactor. In an attempt to propose a mechanism for the carboxylation of catechol by DHBDC_Ec, QM calculations revealed that the transient formation of a 1,3-dipolar cycloaddition product (as suggested for the decarboxylation of cinnamic acid with ferulic acid decarboxylase from S. cerevisiae8) was highly disfavored (>30 kcal/M). As an alternative, we propose a mono-covalent nucleophile adduct involving a prFMN iminium electrophile (~14 kcal/M).

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Recommended Citation

Kurt Faber, S. Payer, K. Plasch, T. Reiter, V. Resch, C. Wuensch, S. M. Glueck, K. Gruber, G. Steinkellner, T. Pavkov-Keller, F. Himo, and X. Sheng, "Carboxylation of phenols and asymmetric nucleophile addition across C=C bond" in "Enzyme Engineering XXIV", Pierre Monsan, Toulouse White Biotechnology, France Magali Remaud-Simeon, LISBP-INSA, University of Toulouse, France Eds, ECI Symposium Series, (2017). https://dc.engconfintl.org/enzyme_xxiv/136