14203-59-9Relevant articles and documents
Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization
Zhang, Wuyuan,Fueyo, Elena Fernandez,Hollmann, Frank,Martin, Laura Leemans,Pesic, Milja,Wardenga, Rainer,H?hne, Matthias,Schmidt, Sandy
supporting information, p. 80 - 84 (2019/01/04)
In this study, we combined photo-organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo-organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light-driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α-chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two-phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo-organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.
Stereoselective hydroxylation of isophorone by variants of the cytochromes P450 CYP102A1 and CYP101A1
Dezvarei, Shaghayegh,Lee, Joel H.Z.,Bell, Stephen G.
, p. 29 - 37 (2018/04/05)
The stereoselective oxidation of hydrocarbons is an area of research where enzyme biocatalysis can make a substantial impact. The cyclic ketone isophorone was stereoselectively hydroxylated (≥95%) by wild-type CYP102A1 to form (R)-4-hydroxyisophorone, an important chiral synthon and flavour and fragrance compound. CYP102A1 variants were also selective for 4-hydroxyisophorone formation and the product formation rate increased over the wild-type enzyme by up to 285-fold, with the best mutants being R47L/Y51F/I401P and A74G/F87V/L188Q. The latter variant, which contained mutations in the distal substrate binding pocket, was marginally less selective. Combining perfluorodecanoic acid decoy molecules with the rate accelerating variant R47L/Y51F/I401P engendered further improvement with the purified enzymes. However when the decoy molecules were used with A74G/F87V/L188Q the amount of product generated by the enzyme was reduced. Addition of decoy molecules to whole-cell turnovers did not improve the productivity of these CYP102A1 systems. WT CYP101A1 formed significant levels of 7-hydroxyisophorone as a minor product alongside 4-hydroxyisophorone. However the F87W/Y96F/L244A/V247L CYP101A1 mutant was ≥98% selective for (R)-4-hydroxyisophorone. A comparison of the two enzyme systems using whole-cell oxidation reactions showed that the best CYP101A1 variant was able to generate more product. We also characterised that the further oxidation metabolite 4-ketoisophorone was produced and then subsequently reduced to levodione by an endogenous Escherichia coli ene reductase.
Two catalytic systems of l-proline/Cu(II) catalyzed allylic oxidation of olefins with tert-butyl hydroperoxide
Yu, Peng,Zhou, Yin,Yang, Yingwei,Tang, Ruiren
, p. 65403 - 65411 (2016/07/26)
The nontoxic and water-soluble l-proline combined with two different forms of copper(ii): recoverable Cu-Al hydrotalcite-like compounds (Cu-Al HTLcs) and water-soluble CuCl2, as a heterogeneous catalytic system (l-proline/Cu-Al HTLcs) and two-phase catalytic system (l-proline/CuCl2) to catalyze allylic oxidation with tert-butyl hydroperoxide. The results showed that l-proline/Cu(ii) is highly active for oxidizing isophorone (IP) into ketoisophorone (KIP). Maximum catalytic effects were afforded respectively under the optimal reaction conditions, which obtained 77.9% IP conversion with 74.3% KIP selectivity catalyzed by l-proline/Cu-Al HTLcs and 73.5% conversion with 81.6% selectivity by l-proline/CuCl2. Recycling experiments of the two catalytic systems of l-proline/Cu(ii) showed they are stable and recyclable for at least six cycles with appreciable catalytic activity. And various hydrocarbons could be smoothly transformed into corresponding ketones with satisfactory conversion and selectivity by the two catalytic systems.
