Florine Cavelier

Studies of selective Boc removal in the presence of silyl ethers

Abstract The selective removal of N-Boc protection can be obtained in the presence of either TBDMS or TBDPS ethers. On the basis of promising results from the literature, we first tried sonication, that failed, whereas the exclusive cleavage of the Boc group was successfully achieved by a saturated solution of HCl in ethyl acetate.

NEW SYNTHESIS OF THE CYCLIC TETRAPEPTIDE TENTOXIN EMPLOYING AN AZLACTONE AS KEY INTERMEDIATE

Abstract An improved preparation of the cyclic tetrapeptide Tentoxin is reported employing an azlactone as key intermediate. This new synthetic route offers the advantage over existing methodologies that the dehydro amino acid would easily be varied, thus allowing the simple preparation of analogues.

All-L-Leu-Pro-Leu-Pro: a challenging cyclization.

In this paper, we report the difficult synthesis of cyclo(Leu‐Pro‐Leu‐Pro). While the cyclization of Leu‐Pro‐Leu‐D‐Pro did not cause problems, the all‐L‐peptide afforded cyclodimer rather than cyclotetrapeptide (cyclomonomer). A first attempt using our reversible backbone substitution methodology failed. However, we were successful in obtaining the desired cyclo(Leu‐Pro‐Leu‐Pro) by decreasing the concentration. The ratio of cyclomonomer to cyclodimer was raised to 1:1.1 using BOP and 1:0.6 using HATU under our high dilution condition. The structures of the cyclopeptides were confidently assigned by electrospray ionization mass spectrometry and NMR. Copyright

A first approach to asymmetric protonation via a polymer supported chiral proton donor

Abstract Asymmetric protonation of achiral silyl enol ethers employing chiral proton donors is described for the first time. We have obtained modest enantiomeric excesses by carrying out these reactions in homogeneous solution. The subject of this paper is to report in a preliminary fashion the substantially improved asymmetric induction that can be achieved by supporting the proton donor on a polymeric resin (up to 94% ee). A temperature effect is observed and discussed.

Natural cyclopeptides as leads for novel pesticides: tentoxin and destruxin†

Difficulties in synthesis make natural cyclopeptides challenging targets for chemists. Our interest focused on two natural toxic cyclopeptide series produced by pathogenic fungi: tentoxin, [cyclo-(N-MeAla 1 -Leu 2 -N-MeΔ z Phe 3 -Gly 4 )] and the destruxins [cyclo-(Pro 1 -Ile 2 -N-MeVal 3 -N-MeAla 4 -β-Ala 5 -HA 6 )]. The total syntheses of these two bioactive series were optimised, and several analogues were designed and synthesised to establish structure-activity relationships. The importance of synthetic analogues in the identification of molecular targets and the explanation of mechanisms of action was demonstrated. Such systematic investigations can determine the crucial features responsible for the activity of the natural compound and help the design of more powerful or more selective products.

Isolation, structure and synthesis of mahafacyclin B, a cyclic heptapeptide from the latex of Jatropha mahafalensis

Mahafacyclin B is a cyclic heptapeptide with antimalarial activity isolated from the latex of Jatropha mahafalensis. The structure is elucidated by chemical degradation, tandem mass spectrometry, homo- and heteronuclear NMR experiments, and confirmed by synthesis.

Deracemization of silyl enol ethers

Abstract The deracemization by enantioselective protonation of silyl enol ethers was tested using 2,2-dimethyl 5-phenyl 1,3-dioxolan 4-one 1 . The results obtained, especially with pantolactone as a chiral proton donor, are better than when the deracemization is carried out with the lithium enolate of 1 .

A side-reaction in the SPPS of Trp-containing peptides.

Syntheses of several Trp‐containing peptides on a Wang solid support afforded significant amounts of a side‐product. 1H‐NMR and MS data showed that an unexpected alkylation by the linker has occurred on the indole nucleus. This was observed whatever the scavenger used, and whatever the position of the Trp residue in the sequence, unless it was in the C‐terminal position. Copyright

Study of a lipophilic captopril analogue binding to angiotensin I converting enzyme.

Human ACE is a central component of the renin–angiotensin system and a major therapeutic target for cardiovascular diseases. The somatic form of the enzyme (sACE) comprises two homologous metallopeptidase domains (N and C), each bearing a zinc active site with similar but distinct substrate and inhibitor specificities. In this study, we present the biological activity of silacaptopril, a silylated analogue of captopril, and its binding affinity towards ACE. Based on the recently determined crystal structures of both the ACE domains, a series of docking calculations were carried out in order to study the structural characteristics and the binding properties of silacaptopril and its analogues with ACE. Copyright

DESTRUXIN ANALOGUES : DEPSI PEPTIDIC BOND REPLACEMENT BY AMIDE BOND

Abstract In order to determine the importance of the depsi bond present in natural destruxins, we have investigated the replacement of this ester bond by an amide bond, leading to a new family of analogues. Synthesis of six specific members of this new class of compounds is reported. Since none of these cyclopeptides showed any biological activity, we undoubtedly proved that the depside group is a requisite for insecticide effect.