The stereoselective synthesis of chiral 1,3‐diols with the aid of biocatalysts is an attractive tool in organic chemistry. Besides the reduction of diketones, an alternative approach consists of the stereoselective reduction of β‐hydroxy ketones (aldols). Thus, we screened for an alcohol dehydrogenase (ADH) that would selectively reduce a β‐hydroxy‐β‐trifluoromethyl ketone. One potential starting material for this process is readily available by aldol addition of acetone to 2,2,2‐trifluoroacetophenone. Over 200 strains were screened, and only a few yeast strains showed stereoselective reduction activities. The enzyme responsible for the reduction of the β‐hydroxy‐β‐trifluoromethyl ketone was identified after purification and subsequent MALDI‐TOF mass spectrometric analysis. As a result, a new NADP+‐dependent ADH from Pichia pastoris (PPADH) was identified and confirmed to be capable of stereospecific and diastereoselective reduction of the β‐hydroxy‐β‐trifluoromethyl ketone to its corresponding 1,3‐diol. The gene encoding PPADH was cloned and heterologously expressed in Escherichia coli BL21(DE3). To determine the influence of an N‐ or C‐terminal His‐tag fusion, three different recombinant plasmids were constructed. Interestingly, the variant with the N‐terminal His‐tag showed the highest activity; consequently, this variant was purified and characterized. Kinetic parameters and the dependency of activity on pH and temperature were determined. PPADH shows a substrate preference for the reduction of linear and branched aliphatic aldehydes. Surprisingly, the enzyme shows no comparable activity towards ketones other than the β‐hydroxy‐β‐trifluoromethyl ketone. 相似文献
A dual catalytic system has been developed following the screening of a series of chiral primary amine catalysts and chiral phosphoric acid catalysts for the Michael addition of cyclic ketones to nitroolefins bearing only one α‐substituent. The resulting γ‐nitro ketones, which contain a substituent on the carbon connected to the nitro group, were formed in excellent yields (>80%) with high levels of stereoselectivity (up to 94:6 dr and 98% ee) when the reaction was performed in benzene at 0 °C with 10 mol% of the optimal amine/phosphoric acid combination (1:1) as a catalyst. Subsequent reduction of the nitro group followed by intramolecular reductive amination could afford optically active cis‐octahydroindole analogues bearing a non‐functional substituent at their 2‐position.
This review surveys the recent developments in enantioselective titanium‐catalyzed cyanation reactions of carbonyl compounds, covering the literature since the beginning of 2008. It well demonstrates that this reaction constitutes an important tool in organic synthesis, still attracting a considerable interest due to the potential use of enantiopure cyanohydrins as natural products and useful synthetic intermediates in the synthesis of biologically active molecules. Abbreviations: Ac: acetyl; Ar: aryl; BINOL: 1,1′‐bi‐2‐naphthol; BINOLAM: bis(diethylaminomethyl)‐1,1‘‐binaphthol; Bn: benzyl; Cy: cyclohexyl; DFT: density functional theory; DMAP: 4‐(dimethylamino)pyridine; ee: enantiomeric excess; Naph: naphthyl; r.t.: room temperature; salen: 1,2‐bis(salicylidenamino)ethane; TADDOL: α,α,α′,α′‐tetraphenyl‐2,2‐dimethyl‐1,3‐dioxolane‐4,5‐dimethanol; TEA: trimethylamine; THF: tetrahydrofuran; TMS: trimethylsilyl; Tol: tolyl.
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