Kassoum Nacro

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.

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.

Conformationally constrained analogues of diacylglycerol (DAG). Part 19: Asymmetric syntheses of (3R)- and (3S)-3-hydroxy-4,4-disubstituted heptono-1,4-lactones as protein kinase C (PK-C) ligands with increased hydrophilicity☆

Abstract The stereospecific introduction of ( R )- and ( S )-OH groups at position C-3 of two diacylglycerol γ-lactones (DAG-lactones) previously identified as strong protein kinase C (PK-C) ligands is presented. The compounds were designed to investigate whether the extra OH group in a specific orientation could establish an additional hydrogen bond with the C1 domain of PK-C, thus providing a DAG analogue with reduced lipophilicity. The OH groups were introduced following two different diastereoselective multistep syntheses starting from diacetone- d -glucose. The PK-C binding affinities for the new compounds were weaker in comparison to those of the parent compounds, suggesting that the extra OH does not engage efficiently in hydrogen bonding at the receptor.

Design and synthesis of 4-heteroaryl 1,2,3,4-tetrahydroisoquinolines as triple reuptake inhibitors.

A series of 4-bicyclic heteroaryl 1,2,3,4-tetrahydroisoquinoline inhibitors of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) was discovered. The synthesis and structure-activity relationship (SAR) of these triple reuptake inhibitors (TRIs) will be discussed. Compound 10i (AMR-2), a very potent inhibitor of SERT, NET, and DAT, showed efficacy in the rat forced-swim and mouse tail suspension models with minimum effective doses of 0.3 and 1 mg/kg (po), respectively. At efficacious doses in these assays, 10i exhibited substantial occupancy levels at the three transporters in both rat and mouse brain. The study of the metabolism of 10i revealed the formation of a significant active metabolite, compound 13.

Synthèse de 2′-désoxynucléosides substitués en C-5′

Abstract Stereocontrolled lactonisation of γ,δ-epoxy β-hydroxyesters provides, after reduction, 2-deoxysugars in pyrano or furano form. After appropriate protections of the hydroxyl functions, these sugars can be converted to various 2′-deoxynucleosides with different configuration of the sugar moiety and an extra functionalisation at C-5.

Influence of the nature and substitution of chiral 2,3-epoxy alcohol derivatives on the enantiomeric elution order on chiralcel OD column

ABSTRACT A number of 2,3-epoxy alcohol derivatives (1–16), obtained either asracemates or through the Sharpless asymmetric epoxidation reaction, were studied ona Chiralcel OD column. Nearly all compounds exhibit good enantioselective resolutionon this chiral support. The order of elution of enantiomers is reversed between nerol andgeraniol compounds. For 2,3-epoxy alcohols bearing a remote alkoxy (or silyloxy) group,the order of the enantiomeric elution alternates with the number n (n = 1–3) of methy-lenic groups present between the epoxide ring and the terminal OR (R=p−BrBn orOSitBuPh 2 ) functionality. In the case of trans 2,3-epoxy alcohols for the same number n,the order of elution is reversed when changing the terminal group −OSi to −OR. Thelatter group greatly improves the separation of the two enantiomers. KEY WORDS: 2,3-epoxyalcohols; enantiomeric elution order; protective groups; chain length influenceFor the last decade, intense interest has focused on thedevelopment of synthetic methods leading to optically ac-tive synthons possessing a 1,2, 1,3, 1,2,3 polyhydroxylatedframe.