Synthesis of Enantiomerically Enriched 2‐Hydroxymethylalkanoic Acids by Oxidative Desymmetrisation of Achiral 1,3‐Diols Mediated by Acetobacter aceti

Abstract

The stereoselective desymmetrisation of achiral 2‐alkyl‐1,3‐diols is performed by oxidation of one of the two enantiotopic primary alcohol moieties by means of Acetobacter aceti MIM 2000/28 to afford the corresponding chiral 2‐hydroxymethyl alkanoic acids (up to 94 % ee). The procedure, carried out in aqueous medium under mild conditions of pH, temperature and pressure, contributes to enlarge the portfolio of enzymatic oxidations available to organic chemists for the development of sustainable manufacturing processes.

Bioprocess Intensification Using Flow Reactors: Stereoselective Oxidation of Achiral 1,3-diols with Immobilized Acetobacter Aceti

“…Considering the good results obtained with compound 1a and the general advantages related to immobilized cells, the biotransformation of achiral 2-alkyl-1,3-diols 1a-d was carried out under the conditions optimized for 1a (Scheme 1). All the tested substrates gave the desired chiral 2-hydroxymethyl alkanoic acid as the major product, and only small amounts of the intermediate aldehydes were observed during the reaction ( Figure 1); enantioselectivity was not affected by immobilization and resulted in the same with free cells [15]. Reaction rates showed a strong dependence on the steric hindrance at the C2 position.…”

“…The production of structurally diverse aldehydes [7], aldoximes [8], lactones [9], and carboxylic acids [10,11] has been achieved using whole cells of acetic acid bacteria, often with high enantioselectivity [12,13]. Stereoselective oxidation of achiral 2-alkyl-1,3-diols has been previously performed in an aqueous solution at room temperature using free whole cells of acetic acid bacteria to afford the corresponding chiral 2-hydroxymethyl alkanoic acids [14,15]. Oxidation of one of the two enantiotopic primary alcohols allowed for desymmetrization of the achiral substrates, furnishing the desired 2-hydroxymethyl alkanoic acids with medium-to-high enantiomeric excesses [15].…”

“…Stereoselective oxidation of achiral 2-alkyl-1,3-diols has been previously performed in an aqueous solution at room temperature using free whole cells of acetic acid bacteria to afford the corresponding chiral 2-hydroxymethyl alkanoic acids [14,15]. Oxidation of one of the two enantiotopic primary alcohols allowed for desymmetrization of the achiral substrates, furnishing the desired 2-hydroxymethyl alkanoic acids with medium-to-high enantiomeric excesses [15]. Low productivity and side product formation were the main drawbacks of this biotransformation; in fact, formation of the corresponding α-methylenic alkanoic acids and α-methyl alkanoic acids were observed due to concurrent dehydration, in particular when the substituent in 2-position was ethyl or n-propyl [15].…”

Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones

“…The scarcity of experimental data on the bioreduction of -nitroketones, especially for aromatic derivatives, and the current need for biocatalysed synthesis of chiral building blocks for pharmaceutical applications [27][28][29][30][31] led us to investigate the use of commercial alcohol dehydrogenases for the enantioselective reduction of aryl and alkyl α-nitroketones 3 in controlled reaction conditions. We also studied the further manipulation of specific nitroalcohols 1 to prepare aminoalcohols 2, which have been already employed as key intermediates for the synthesis of active pharmaceutical ingredients, such as levamisole and (R)-tembamide.…”

Chemoenzymatic Synthesis in Flow Reactors: A Rapid and Convenient Preparation of Captopril

“…Our flow‐based synthetic route to obtain captopril includes a first biocatalyzed heterogeneous regio‐ and stereoselective oxidation reaction starting from a cheap prochiral diol (2‐methyl‐1,3‐propandiol, 1 ) followed, after isolation of carboxylic acid 2 , by three sequential chemical steps. The biocatalyzed flow oxidation offers an efficient alternative for environmentally benign oxidations in answer to the critical economic and environmental issues that urgently demand greener, more atom‐efficient and scalable oxidation methods .…”