Marc Rolland

Electrochemical grafting of long spacer arms of hexamethyldiamine on a screen printed carbon electrode surface: application in target induced ochratoxin A electrochemical aptasensor

A novel strategy based on direct electrochemistry of amino group on screen printed carbon electrode surface (SPCE) was purposed. The purposed method was employed for the label free detection of ochratoxin A (OTA). A long spacer arm of hexamethyldiamine was immobilized on SPCE via electrochemical oxidation of its terminal amino-group. The activated carboxy-aptamer was covalently linked to other amino terminal group of immobilized hexamethyldiamine. The designed immobilized macromolecules resulted in the formation of long clusters on SPCE surface, while aptamer acted as gate to block the entrance of these clusters. The aptamer gates were closed due to change in conformation of aptamer upon target analyte binding, decreasing the electrochemical signal. The decrease in electrochemical signal was used for the detection of target molecule.

Dynamic kinetic resolution of racemic N-phthalyl amino acids using (S)-α-methylpantolactone as the chiral auxiliary

Abstract A dynamic kinetic resolution of racemic N-phthalyl amino acids by stereoselective esterification was examined using (S)-α-methylpantolactone as the chiral auxiliary. The reaction of various racemic N-phthalyl amino acids with this chiral alcohol in the presence of both DCC and DMAP afforded predominantly the (S,S)-esters in nearly quantitative yield.

Asymmetric Synthesis of (S)-β2-Homoarylglycines

The synthesis of racemic N-phthalyl β2-homoarylglycines 5 and their asymmetric transformation have been investigated. The key step is the stereoselective addition of the (R)-pantolactone to the corresponding prochiral ketene 7.

Synthesis of enantiomerically pure (3R,4R,5R)-4-hydroxy isoleucine lactone

Abstract A short four-step synthesis of (3 R ,4 R ,5 R )-4-hydroxyisoleucine lactone with total control of stereochemistry is reported, the key intermediate being the didehydroamino acid derivative arising from an aldol dehydration reaction between a glycine anion equivalent and butan-2,3-dione.

C‑Glycoside Mimetics Inhibit Glioma Stem Cell Proliferation, Migration, and Invasion

This paper reports the design and synthesis of C-glycoside mimetics (d-glycero-d-talo- and d-glycero-d-galactopyranose analogues), a subset of the recently published phostines, belonging to the [1,2]oxaphosphinane core. Eighteen new compounds were tested against 11 cancer cell types belonging to six categories of tumor tissues and three different species. The hit compound 5.3d inhibited invasion and migration of both GBM stem cells (Gli7 and Gli4) and GBM cancer cell lines (C6, SNB75) on fibronectin, vitronectin, and laminin. Ki values for Gli7 and Gli4 migration inhibition on fibronectin were 16 and 31 nM respectively. Ki values for invasion inhibition in a 3D system were 46 nM for Gli7 and 290 nM for Gli4. These activities were associated with an antiproliferative effect on Gli4 (EC50 = 5.20 μM) and Gli7 (EC50 = 2.33 μM). In conclusion, the heptopyranose mimetic 5.3d, devoid of toxicity on astrocyte and cortical neuron cultures at concentrations below 100 μM, opens new therapeutic perspectives against glioblastoma.

Optically pure β-substituted β-hydroxy aspartates as glutamate transporter blockers

A short asymmetric synthesis of optically pure beta-substituted beta-hydroxy aspartates is described. The key step is an aldol reaction between a glycine enolate derived from an oxazinone intermediate used as chiral auxiliary and various alpha-keto esters. Excellent diastereomeric excesses are obtained.

Structural isomers of iron(III) N-methyl diethanolaminate as sol–gel precursors for iron-based oxide nanomaterials

A new homoleptic iron(III) complex, [Fe4(mdea)6]·6CHCl3 (mdeaH2 = N-methyl diethanolamine), isolated in star- or chair-shaped isomeric forms, was evaluated and compared with other homoleptic iron(III) aminoalkoxides for different sol–gel parameters to stabilize nano-sized colloidal suspensions, and to elaborate magnetic Fe2O3 and BiFeO3 nanoparticles as well as thin films by spin coating.

N-acetyl oxyntomodulin30–37: pharmacokinetics and activity on gastric acid secretion

SummaryOxyntomodulin, an intestinal hormone which inhibits gastric acid secretion, is composed of glucagon and a C-terminal octapeptide. This octapeptide mimics the biological activity of the hormone. We have studied the activity of the N-acetyl octapeptide, partially protected against enzymatic degradation, on pentagastrin-, histamine- and milk meal-stimulated secretion in conscious rats and compared it to that of oxyntomodulin and its derivatives. The N-acetylated octapeptide had a 3-fold higher potency than the octapeptide on pentagastrin-stimulated secretion. On histamine-stimulated secretion, the differences between the acetylated and the free octapeptides were that the former displayed a dose-response curve parallel to that of oxyntomodulin and a 4-fold higher potency. The increase in potency appears to be related in part to a decrease in the metabolic clearance rate in vivo (6-fold) and, in vitro, to an increase in half-life (3-fold) when incubated with rat liver plasma membranes. Similarly to the free octapeptide, the acetylated form decreased acid secretion stimulated by a milk meal, when infused before the meal. Acetylation of the Lysine side chains resulted in a totally inactive molecule. The results indicate that acetylating the N-terminus of the octapeptide of oxyntomodulin increases the similarities with the natural hormone. The still large difference in potency (≈ 40-fold) between the 37-amino acid peptide and its acetylated 8-amino acid derivative is explained by the higher (≈ 40-fold) metabolic clearance rate (MCR) of the latter, indicating that further decreasing this parameter, in particular by protecting the short peptide from the enzymatic degradation, should result in a potent and efficient molecule, usable for pharmacological research and therapeutics.

Diastereoselective esterification of (±)-N-trifluoroacetyl pipecolic acid using (S)-α-methyl pantolactone: synthesis of (S)-N-Boc pipecolic acid and (S)-N-Boc-2-piperidinemethanol

Abstract Racemic N -trifluoroacetyl pipecolic acid has been converted into ( S )- N -Boc-pipecolic acid or ( S )- N -Boc-2-piperidinemethanol by DCC/DMAP-induced diastereoselective esterification with ( S )-α-methyl pantolactone, followed by a saponification or a reduction reaction and N -Boc protection.

First asymmetric synthesis of (R)-(−)-α-phenyl δ-amino valeric acid

Abstract An efficient synthesis of the ( R )-(−)-α-phenyl δ-amino valeric acid 1 is described starting from commercially available compounds. The key intermediate in this synthesis is the corresponding totally protected prochiral ketene.