Enantioselective synthesis of α-hydroxyketones using the ditox asymmetric building block (original) (raw)

Enzymatic diastereo- and enantioselective synthesis of α-alkyl-α,β-dihydroxyketones

Organic & Biomolecular Chemistry, 2011

An enzymatic strategy for the preparation of optically pure a-alkyl-a,b-dihydroxyketones is reported. Homo-and cross-coupling reactions of a-diketones catalyzed by acetylacetoin synthase (AAS) produce a set of a-alkyl-a-hydroxy-b-diketones (30-60%, ee 67-90%), which in turn are reduced regio-, diastereo-, and enantioselectively to the corresponding chiral a-alkyl-a,b-dihydroxyketones (60-70%, ee >95%) using acetylacetoin reductase (AAR) as catalyst. Both enzymes are obtained from Bacillus licheniformis and used in a crude form. The relative syn stereochemistry of the enantiopure a,b-dihydroxy products is assigned by NOE experiments, whereas their absolute configuration is determined by conversion of the selected 3,4-dihydroxy-3-methyl-pentan-2-one to the natural product (+)-citreodiol.

α,α′-Dihydroxyketone formation using aromatic and heteroaromatic aldehydes with evolved transketolase enzymes

Chemical Communications, 2010

Transketolase mutants have been identified that accept aromatic acceptors with good stereoselectivities, in particular benzaldehyde for which the wild type enzyme showed no activity. The advantages of using biocatalysts as a sustainable resource 10 in synthesis are well established and includes their potential to achieve high regio-and stereoselectivities. 1,2 Transketolase (TK) (E.C.2.2.1.1) is a thiamine diphosphate (ThDP) dependent carbon-carbon bond forming enzyme. 3 In vivo it reversibly transfers a two carbon ketol unit to D-erythrose-4-65 Notes and references

Promiscuous Substrate Binding Explains the Enzymatic Stereo- and Regiocontrolled Synthesis of Enantiopure Hydroxy Ketones and Diols

Advanced Synthesis & Catalysis, 2009

Regio-and stereoselective reductions of several diketones to afford enantiopure hydroxy ketones or diols were accomplished using isolated alcohol dehydrogenases (ADHs). Results could be rationalised taking into account different (promiscuous) substrate-binding modes in the active site of the enzyme. Furthermore, interesting natural cyclic diketones were also reduced with high regio-and stereoselectivity. Some of the 1,2-and 1,3-diketones used in this study were reduced by employing a low excess of the hydrogen donor (2-propanol) due to the quasi-irreversibility of these ADH-catalysed processes. Thus, using lower quantities of co-substrate, scale-up could be easily achieved.

Thiamine-Diphosphate-Dependent Enzymes as Catalytic Tools for the Asymmetric Benzoin-Type Reaction

European Journal of Organic Chemistry, 2016

Benzoin-type reactions allow the generation of αhydroxy ketones through the (formal) carboligation of two aldehyde reactants. The synthetic relevance of the products and the wide distribution of the α-hydroxy ketone functionality in bioactive natural compounds have provided the motivation for intensive research efforts directed towards the development of ever more efficient and selective catalysts for reactions of this class. As in many other areas of study, the solution developed in nature-that is, the utilization of thiamine-diphosphate-de-[a]

A Simple Synthetic Route to Enantiopure α-Hydroxy Ketone Derivatives by Asymmetric Hydrogenation

Advanced Synthesis & Catalysis, 2012

High enantioselectivities (up to 99% ee) have been observed for the catalytic asymmetric hydrogenation of the a-ketone enol acetates. Duan-Phos has been proved to be the most effective ligand for this reaction. The high yield and enantioselectivity of the asymmetric hydrogenation of the a-ketone enol acetates represents a feasible synthetic route to important pharmaceutical building blocks: a-hydroxy ketones.

Asymmetric Synthesis of Aliphatic 2Hydroxy Ketones by Enzymatic Carboligation of Aldehydes

European Journal of Organic Chemistry, 2007

Benzaldehyde lyase (BAL) and benzoylformate decarboxylase (BFD) catalyse the asymmetric ligation of aliphatic aldehydes to afford enantiomerically enriched 2-hydroxy ketones. Carboligation of linear aldehydes with both enzymes results in high levels of conversion and in enantioselectivities of up to 80 % ee. In cases involving branched aliphatic aldehydes, BAL enables the carboligation of 3-methylbutanal with a high level of conversion and an enantioselectivity of 89 % ee.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)