Liliane Gorrichon

A molecular model for cinnamyl alcohol dehydrogenase, a plant aromatic alcohol dehydrogenase involved in lignification

The plant aromatic alcohol dehydrogenase, cinnamyl alcohol dehydrogenase (CAD2 from Eucalyptus) was found by sequence analysis of its cloned gene to be homologous to a range of dehydrogenases including alcohol dehydrogenases, L-threonine-3-dehydrogenase, D-xylose reductase and sorbitol dehydrogenase. A homology model of CAD2 was built using the X-ray crystallographic coordinates of horse-liver alcohol dehydrogenase to provide the template, with additional modelling input from other analogous regions of structure from similar enzymes where necessary. The structural model thus produced rationalised the Zn-binding properties of CAD2, indicated the possession of a Rossmann fold (GXGXXG motif), and explained the class A stereospecificity (pro-R hydrogen removal from substrate alcohol) and aromatic substrate specificity of the enzyme. A range of potential ligands was designed based on the homology model and tested as inhibitors of CAD2 and horse liver alcohol dehydrogenase.

Spontaneous aldol and Michael additions of simple enoxytrimethylsilanes in DMSO

Abstract Activation of simple trimethylsilyl ketene acetals by dipolar aprotic solvents has been evidenced, allowing efficient solvent assisted aldol and Michael additions under extremely simple, mild and metal free conditions.

Bicyclic peroxides in the G factors series: synthesis and electrochemical studies

Abstract Endoperoxides belonging to the family of G factors have been synthesised under Mannich type conditions. The structure of different diastereoisomers has been established on the basis of NMR experiments. Their cathodic peak potentials have been determined by thin-layer electrochemistry under potentiostatic conditions, and compared to that of artemisinin.

Alkylation of natural endoperoxide G3-factor. Synthesis and antimalarial activity studies

Alkylation of the peroxyhemiketal function is described and all synthesised endoperoxides show good antimalarial activity. New rearrangement reactions in the presence of CsCO3, and preliminary results on Fe(II) chemical reduction of the O-O bond are presented.

Diastereoface differentiation in addition of lithium enolates to chiral α,β-epoxyaldehydes

Abstract The aldolisation reaction of lithium ester enolates with chiral α,β-epoxyaldehydes 2a–2f has been investigated. The reaction proceeds with diastereofacial preference in favour of the anti isomer ( anti:syn ≈ 4:1) and can be greatly enhanced in the case of cis α,β-epoxy-aldehydes 2a–2c by a synergic effect of temperature and enolate excess ( anti:syn 13:1). The Felkin-Ahn model can explain the results obtained on asymmetric induction.

Synthesis of Syncarpic Acid and Related β-OXO δ-Enol Lactone via Selective O- or C- Acylation of Preformed Enolates

Abstract Syncarpic acid 1 and the β-oxo δ-enol lactone isomer 2 have been prepared in two steps starting from the readily available ketoester 6. Selective C- or O-acylation of the SiMe3 or Li enolates of 6 and intramolecular cyclisation of the new adducts 8 or 9 lead to 1 and 2 in good yields (48% and 52% respectively starting from ethyl isobutyrate)

Stereoselective synthesis of five and/or six membered ring hydroxylactones obtained by Lewis acid mediated reaction of γ,δ-epoxy-β-hydroxyesters; access to 5-methylated 2-deoxysugars.

Abstract A stereoselective route to six and/or five membered ring lactones from optically active γ,δ-epoxy-β-hydroxyesters obtained from nerol and geraniol has been developed. The intramolecular cyclization by epoxide ring opening occurred via activation of 6-endo over the usually favoured 5-exo, and the application of this technology to the stereocontrolled synthesis of 5-methylated 2-deoxysugars was achieved.

Diastereoselection in the addition of enolates to chiral α,β-epoxyaldehydes

Abstract The stereochemistry of addition of lithium enolates to the α,β-epoxyaldehydes 1z – 3 has been investigated. Moderate to high diastereoselectivity (up to 13:1) is obtained in favour of the anti isomer, which is explained by the Felkin-Anh model for asymmetric induction.

Stereoselective Preparation of Protected Thymine Polyoxin C and Approaches Towards Synthesis of Its C2′‐Modified Analogues

Polyoxins form an important class of pyrimidine peptide antifungal agents. The preparation of thymine polyoxin C, which is the nucleosidic component of some polyoxins, is reported, together with attempts to synthesize C2′-fluoro analogues. Epimeric 3-hydroxyazidolactones 2a and 2b, obtained from diastereoisomeric epoxy hydroxy esters, were dehydrated to afford butenolide 3. Dihydroxylation and further functional manipulation yielded thymine polyoxin C. Attempts to form the 2,2′-anhydronucleoside and to direct nucleophilic fluorination with DAST on a monoprotected nucleoside were unsuccessful. Electrophilic fluorination of azidolactone with NFSI permitted the formation of an α-fluorolactone, which is an interesting intermediate for the preparation of a C2′-fluoro analogue.

Enhanced diastereoselectivity in the addition of ester enolate to optically active α,β-epoxyaldehydes obtained from nerol and geraniol

Abstract Optically active α,β-epoxyaldehydes obtained from nerol and geraniol were allowed to react with lithium tert-butylacetate. The diastereofacial preference of the aldolisation reaction was always anti (“Si”face attack of the carbonyl). The best diastereoselectivity ever observed in these series (>99 : anti : syn ) was obtained for the α,β-epoxyneral aldolisation.