Jacqueline Mahuteau

Effect of camphor/cyclodextrin complexation on the stability of O/W/O multiple emulsions.

Camphor (CA) encapsulation in oil/water/oil multiple emulsions prepared with cyclodextrin disturbs the emulsifier potential of alpha- and beta-natural cyclodextrins (CD). It was suggested that the size and geometrical fit between the CD cavity and CA could induce CD/CA complex formation in place of emulsifier formation leading to perturbation of emulsion stability. The complexation between CA and alpha-, beta- or gamma-CD in solution in the presence of oil phase are confirmed by phase-solubility diagrams, circular dichroism and 1H NMR. Furthermore, in order to mimic the emulsion system, CD/CA/soybean oil ternary dispersions were prepared to observe the complexation behavior of alpha-, beta- or gamma-CD/CA by circular dichroism. X-ray diffraction on emulsion samples prepared with alpha- and beta-CD confirms that the precipitates observed in emulsions are probably composed of crystals of CD/CA complexes. A preliminary study of the interaction between drug and CD before the formulation seems indispensable to prevent the risk of incompatibility.

Study of the binding affinity of oligo-tetrahydrofuranic γ-lactones with cations

Abstract Tetrahydrofuranic γ-lactone derivatives have shown interesting cytotoxic activities which can be explained by an ionophoric ability. Indeed, divalent cations show a higher affinity than monovalent ions with these lactones, with a dependancy on the stereochemical relationships of the stereogenic centres of the molecules.

Regioselective Annulation of 1,5-Diketones: Access to Functionalized Hagemann’s Esters

The synthesis of the “functionalized” Hagemann’s ester (S)-18 was investigated. The common starting material in these approaches was enamino ester (S,Z)-5, which was prepared through the condensation of keto diester 4 with (S)-1-phenylethylamine. The Michael addition reaction of 5 with methyl vinyl ketone gave the expected adduct (S)-6 with an ee ⩾ 95%. However, all attempts at annulation of 6 invariably afforded the unwanted cyclohexenone derivatives 7 or 8. The addition of 5 to Nazarov reagent 9 furnished adduct (S)-10 with an ee ⩾ 95%. The Triton B-induced annulation of 10 unexpectedly gave aldol 11. Depending on the reaction conditions, annulation of 11 afforded either the bicyclic lactone 12, or cyclohexenones 13 or 15. An efficient way of reversing the sense of the regiochemistry of the previous annulation was found, based on the use of diethyl 2-oxo-3-vinylphosphonate (16) as a Michael acceptor. Thus, the condensation of 5 with 16 gave (S)-17 with an ee ⩾ 95%, and cyclization of (S)-17 under Horner−Wadsworth−Emmons conditions gave the desired Hagemann’s ester (S)-18. The structural assignments for 18 were ascertained by chemical correlation with the known hydrindenedione (S)-21.

The asymmetric Michael reaction using chiral imines under neutral conditions: Stereochemical evidences in support of a cyclic transition state

Abstract Stereochemical outcome observed in addition [ 6 + 7 ], [ ent - 6 + 15 ] and [ 18 + methyl acrylate] have been rationalized by evoking the participation of the corresponding compact approaches 14, 21 and 22 .

Synthesis and structural determination of new chiral auxiliaries derived from (−)-β-pinene

New chiral auxiliaries, alcohols syn-11a,e and anti-12a,e were readily synthesized in a stereoselective manner from (−)-β-pinene. Their stereochemical determinations have been made on the basis of nOe experiments.

Structure–Activity Relationships of Synthetic Tricyclic Trioxanes Related to Artemisinin: The Unexpected Alkylative Property of a 3‐(Methoxymethyl) Analog

A clear-cut correlation between antimalarial potency and the alkylative property of synthetic tricyclic trioxanes 5–10 is reported. Thus, trioxanes 5 and 7, substituted at the C-5a angular position by a methyl or a cyano group, proved to be completely devoid of antimalarial activity, and did not alkylate the heme model MnIITPP. In contrast, both the anti-Plasmodium activity and the alkylative property were restored in the C-5a-unsubstituted analog 8, bearing a methoxymethyl group at C-3. Reaction of 8 with MnIITPP furnished the covalent adduct 18, resulting from trapping of the methoxymethyl radical by the heme model. All these results reinforce the hypothesis that the metalloporphyrin closely interacts with the peroxide bond of the drug to bring about activation of these trioxane antimalarial agents.

Convenient access to 1,3,5-triaroylbenzenes

Abstract The unusual transformation of β-aryl-β-haloacroleins into valuable triaroylbenzenes is reported by the first time. The convenient sequence takes advantage on the one step access to triaroylbenzenes. This work establishes that the presence of amine is required for the trimerization procedure since it is involved in the formation of iminium–enamine intermediate A.

A NOVEL ASYMMETRIC SYNTHESIS OF 2,5 -DIALKYLPYRROLIDINES

Abstract ZnCl 2 -promoted cyclization of enamino ester 8 furnished a 1.5:1 mixture of pyrrolidines 9 and 10 . NaBH 4 -reduction of this mixture gave cis and trans -2,5-dialkylpyrrolidines 12 and 13 in the ratio 2:1. The latter derivative was obtained in its 2 S , 5 S enantiomerically pure form.

Asymmetric bridging annulation reaction involving the intramolecular conjugate addition of chiral imines to enoates: Access to a polycyclic system related to the taxane core

Abstract (R)-1-phenylethylamine-induced cyclization of ketoenoate 24 led to a 2:1 mixture of “all-cis” polycyclic adducts 25 and 26 , structurally related to the taxane series.

Synthetic approaches to Cinchona alkaloids: the C-8/C-9 disconnection strategy

When conducted in DMSO, the Hunigs base-promoted condensation of 3-quinuclidinone with quinoline-4-carboxaldehyde gave an equimolar mixture of epimeric aldols 8 with an excellent yield.