Henri Veschambre

Chemical and biological synthesis of chiral epoxides

Iv. Introduction 8886 Chemical Synthesis of Chiral Epoxides 8887 1. Epoxidation of olefins with per&d8 8887 1.1. Enantioselective epoxidation of alkenes 8887 1.2. Enantioselective epoxidation of allylic alcohols 8888 1.3. Conclusion 8889 2. Epoxidation catalyzed by metals: Sharpless method 8889 2.1. Use of transition metals 8889 2.2. Pmcursors of the Sharpless reagent 8889 2.3. The Sharpless reaction 8891 2.4. Conclusion 8894 3. Epoxidation catalyzed by metalloporphyrins 8894 4. Other methods 8898 4.1. From chit-al precursors 8898 4.2. Use of phase-transfer catalysts 8899 4.3. Use of chiral reagents 8900 5. Conclusion 8901 Biological Synthesis of Chiral Epoxides 8901 1. Direct stereospecific epoxidation 8901 1.1. Isolated monooxygenases: the cytochromes P-450 8902 1.2. Bacterial monooxygenases 8906 1.3. Monooxygenases from other microorganisms 8912 1.4. Conclusion 8912 2. Indirect epoxidation 8912 2.1. Use of peroxidases 8912 2.2. Other methods 8915 2.3. Conclusion 8917 3. Enzymatic resolution 8917 3.1. use of lipases 8917 3.2. Enantioselective degradation of epoxides 8918 3.3. Conclusion 8921 4. Conclusion 8921 Conclusion 8921

Fungal biodegradation of a phenylurea herbicide, diuron: structure and toxicity of metabolites.

Microbial degradation, organic synthesis and ecotoxicology were used to investigate the fate of diuron after spreading on soils. Quantitative biodegradation assays were performed with fungal strains, showing that diuron was degraded but not entirely mineralized. The modifications observed consisted in demethylation of the terminal nitrogen atom. The identified metabolites were synthesized in sufficient amounts to confirm their structures and determine their non-target toxicity using four biotests. The two metabolites exhibited higher effects than parent diuron. This limited biodegradability and potential aquatic toxicity suggest that diuron is of higher environmental concern than previously recognized.

Biotransformation of phenylurea herbicides by a soil bacterial strain, Arthrobacter sp. N2: structure, ecotoxicity and fate of diuron metabolite with soil fungi

In order to assess the influence of the aromatic substitution on the ability of a soil bacterial strain, Arthrobacter sp. N2, to degrade phenylurea herbicides, biotransformation assays were performed in mineral medium with resting cells of this soil bacterial strain on three phenylurea herbicides (diuron, chlorotoluron and isoproturon). Each herbicide considered, led to the formation of only one metabolite detected by HPLC analysis. After isolation, the metabolites were identified by NMR and MS, as the corresponding substituted anilines. According to the Microtox test (realized on the bacterium Vibrio fischeri), these metabolites presented non-target toxicity far more important (up to 600 times higher for 4-isopropylaniline) than the parent molecule. For isoproturon and chlorotoluron, the amount of substituted anilines obtained at the end of the biotransformation was very low, whereas the biotransformation of diuron into 3,4-dichloroaniline was almost quantitative. In this last case, the degradation product accumulated in the medium. In soil, other microorganisms are present that might degrade it. So the biotransformation of 3,4-dichloroaniline was then tested with four fungal strains: Aspergillus niger, Beauveria bassiana, Cunninghamella echinulata var. elegans and Mortierella isabellina. The aniline was further transformed with all the microorganisms tested. Only one metabolite was detected by HPLC analysis and after isolation, it was identified to be 3,4-dichloroacetanilide. This acetylated compound led to biological effects less important on V. fischeri than 3,4-dichloroaniline. These results stress the importance of identifying the degradation products to assess the impact of a polluting agent. Indeed, the pollutant may undergo transformation yielding compounds more toxic than the parent molecule.

Isolation, characterization and diuron transformation capacities of a bacterial strain Arthrobacter sp. N2

A bacterial strain able to transform diuron was isolated from a soil by enrichment procedures. Strain isolation was realized by plating on minimal-agarose medium spread with this herbicide and selecting the colonies surrounded by a clear thin halo. One strain was characterized and identified as an Arthrobacter sp. It metabolized diuron and the final transformation product, 3,4-dichloroaniline, was produced in stoichiometric amounts. The transformation of diuron at different concentrations was more efficient in the presence of alternative sources of carbon and nitrogen. The bacterial activity was also evaluated in soil microcosms with a consequent disappearance of diuron and concomitant appearance of 3,4-dichloroaniline, of which the concentration decreased thereafter. Bacterial cells inoculated in the microcosms survived as viable but eventually nonculturable cells.

Common Degradative Pathways of Morpholine, Thiomorpholine, and Piperidine by Mycobacterium aurum MO1: Evidence from 1 H-Nuclear Magnetic Resonance and Ionspray Mass Spectrometry Performed Directly on the Incubation Medium

ABSTRACT In order to see if the biodegradative pathways for morpholine and thiomorpholine during degradation by Mycobacterium aurumMO1 could be generalized to other heterocyclic compounds, the degradation of piperidine by this strain was investigated by performing1H-nuclear magnetic resonance directly with the incubation medium. Ionspray mass spectrometry, performed without purification of the samples, was also used to confirm the structure of some metabolites during morpholine and thiomorpholine degradation. The results obtained with these two techniques suggested a general pathway for degradation of nitrogen heterocyclic compounds by M. aurum MO1. The first step of the degradative pathway is cleavage of the C—N bond; this leads formation of an intermediary amino acid, which is followed by deamination and oxidation of this amino acid into a diacid. Except in the case of thiodiglycolate obtained from thiomorpholine degradation, the dicarboxylates are completely mineralized by the bacterial cells. A comparison with previously published data showed that this pathway could be a general pathway for degradation by other strains of members of the genus Mycobacterium.

A simple and efficient enantioselective synthesis of piperidine alkaloids dihydropinidine and isosolenopsins A, B and C

Abstract A diastereospecific intramolecular Mannich-type reaction, involving enantiopure amine 4 and achiral aldehydes, is employed as the key step of an efficient total enantioselective synthesis of five piperidine alkaloids.

Utilisation des methodes biologiques pour la preparation de synthons chiraux : I-reduction de β-dicetones acycliques par saccharomyces cerevisiae (levure de boulanger)

Abstract The reduction of acyclic β-dikotenes by bakers yeast gave ketols, in many cases with high optical purity. The reaction is easy to carry out and provides chiral molecules of high synthetic interest.

Reduction of α,β-unsaturated ketones by plant suspension cultures

Abstract α,β-Unsaturated ketones were reduced by various plant cells grown under different cultural conditions. The stereochemistry of the reduction of (-)-carvone by Medicago sativa was found to be identical to that obtained with other organisms.

A practical asymmetric synthesis of 2,6-cis-disubstituted piperidines

Abstract A highly diastereoselective intramolecular Mannich reaction involving enantiopure α-methylamine 7 and achiral aldehydes is employed to prepare enantiomerically pure 2,6- cis -disubstituted piperidines. This methodology provides an efficient and selective route to 2,6- cis -disubstituted piperidines, 2,6- cis -disubstituted 4-piperidones and 2,6- cis -disubstituted 4-piperidinols.

Use of biological systems for the preparation of chiral molecules IV: A two-step chemoenzymatic synthesis of a natural pheromone (4R,5S)-(−)-4-methyl 5-hydroxy heptan 3-one, sitophilure.

Abstract Reduction of 4-methyl heptan 3,5-dione 2 by resting cells of Geotrichum candidum provides natural sitophilure (4R,5S)-(−)-4-methyl 5-hydroxy heptan 3-one 1 under anaerobic conditions. Diastereoisomer (4S,5S)-(+)-4-methyl 5-hydroxy heptan 3-one 1a is obtained under aerobic conditions. Starting β-diketone is easily obtained by a one-pot synthesis. Good yield and high enantiomeric excess are obtained for the natural pheromone.