Didier Buisson

Diastereoselective and enantioselective microbial reduction of cyclic alpha-alkyl beta-ketoesters

Abstract The reduction of racemic cyclopenta- and cyclohexanone 2-carboxyesters by various yeast and mould strains was shown to produce different amounts of isomeric beta-hydroxyesters with predominant (1 S ) stereochemistry. With several strains, only one optically pure cis or trans stereoisomer was obtained in high yield, indicating a diastereoselective and enantioselective reduction.

Dynamic resolution and stereoinversion of secondary alcohols by chemo-enzymatic processes

To overcome the maximum 50% yield limitation of classical resolution methods, deracemization processes involving a racemization step (dynamic resolution) or a prochiral intermediate (stereoinversion) have been developed. The use of transition metal complexes as racemizing agents, in combination with an enzymatic reaction, has been successfully extended to the deracemization of a number of simple or functionalized sec-alcohols. A two-enzyme process has been also investigated for their sequential or simultaneous deracemization. Other prominent results arise from an (apparently general) oxidoreduction process catalyzed by a single whole-cell microorganism.

Chemoenzymatic synthesis of conformationally rigid glutamic acid analogues

Abstract All stereomers of cyclohexane and cyclopentane-derived analogues of glutamic acid have been synthesized from the corresponding 3-keto-cycloalkyl carboxylic acid esters by a combination of microbial steps and standard chemical methods.

A Study of the Stereocontrolled Reduction of Aliphatic β-Ketoesters by Geotrichum candidum

The conditions necessary to reduce stereoselectively aliphatic beta-ketoesters by G. candidum have been investigated. Ageing of the mycelium allowed a practical preparation of optically pure (R)-ethyl 3-hydroxybutanoate, as a result of stereoselective reduction, enantioselective metabolism and stereoisomer interconversion. The stereoconversion of 3S-hydroxybutanoate into the 3R-enantiomer via 3-oxoester formation has been demonstrated to be a determining factor in the building of the optical purity of the resulting product. Enantioselective preparations of higher homologous 3R-hydroxyesters are described.

Diastereo- and enantioselective microbiological reduction of 2-methyl 3-oxoalkanoates

Abstract Reduction of 2-methyl 3-oxobutanoate or pentanoate by several fungal strains gave essentially the corresponding and anti (2S,3S)-hydroxyesters in high optical purity.

The microbial reduction of 2-chloro-3-oxoesters

Abstract Several aliphatic or aromatic 2-chloro-3-oxoesters are stereoselectively reduced by yeast or fungal strains, affording in fair to good yield and high enantiomeric excess some of the respective 2-chloro-3-hydroxyester stereoisomers.

Microbial reduction of 1-tetralone 2-carboxyesters as a source of new asymmetric synthons

Abstract The reduction of unsubstituted or methoxy-substituted (±)-2-carboxyethyl-1-tetralones by selected microorganisms affords optically active 1-hydroxy-2-carboxyethyl tetralins which can be used as versatile asymmetric synthons, for example in the preparation of biologically active methoxy-substituted 2R-aminotetralins. 1R,2R-(cis)-hydroxyesters of high optical purity are obtained with yeast strains, while the use of filamentous fungi leads to the enantiomeric 1S,2S-(cis)-hydroxyesters.

Preparation of both enantiomers of a chiral lactone through combined microbiological reduction and oxidation.

The Baeyer-Villiger-like oxidation of (R,S)-2,2,5,5-tetramethyl-4-hydroxy -cyclohexanone by several fungal strains was highly enantioselective, affording a rearranged (S)-hydroxy-γ-lactone. The recovery of the nearly optically pure (R)-hydroxyketone allowed its conversion to the enantiomeric (R)-hydroxylactone through a classical Baeyer-Villiger oxidation.

New chiral building blocks by microbial asymmetric reduction: A direct access to functionalized 2R,3R- and 2S,3R-2-methyl-3-hydroxy butyrate synthons

Abstract The Reduction of 4-O-benzyl-2 -methyl-3-oxo-butyrate esters by several fungal strains produces predominantly (2S,3R)- anti -hydroxyesters in high optical purity. The corresponding (2R,3R)- syn isomer was obtained, with other strains, only in mixture with the anti isomer. These esters are useful precursors for chiral 2-methyl-3-hydroxy-butyrolactone synthons.

Bioelectro-Fenton: A sustainable integrated process for removal of organic pollutants from water: Application to mineralization of metoprolol

The relevant environmental hazard related to the presence of pharmaceuticals in water sources requires the development of high effective and suitable wastewater treatment technologies. In the present work, a hybrid process coupling electro-Fenton (EF) process and aerobic biological treatment (Bio-EF process) was implemented for the efficient and cost-effective mineralization of beta-blocker metoprolol (MPTL) aqueous solutions. Firstly, operating factors influencing EF process were assessed. MTPL solutions were completely mineralized after 4h-electrolysis under optimal operating conditions and BDD anode demonstrated its oxidation superiority. The absolute rate constant of MTPL oxidation byOH (kMTPL) was determined by the competition kinetics method and found to be (1.72±0.04)×10(9)M(-1)s(-1). A reaction pathway for the mineralization of the drug was proposed based on the identification of oxidation by-products. Secondly, EF process was used as pre-treatment. An increase of BOD5/COD ratio from 0.012 to 0.44 was obtained after 1h EF treatment, along with 47% TOC removal and a significant decrease of toxicity, demonstrating the feasibility of a post-biological treatment. Finally, biological treatment successfully oxidized 43% of the total TOC content. An overall 90% mineralization of MPTL solutions was achieved by the Bio-EF process, demonstrating its potentiality for treating wastewater containing pharmaceutical residues.