Fragmentation of DMPC Membranes by a Wedge-Shaped Amphiphilic Cyclodextrin into Bicellar-like Aggregates
Roux, M.; Legrand, F. X.; Bil, A.; Bonnet, V.; Djedaini-Pilard, F.
J. Phys. Chem. B 2023.
Small bilayer lipid aggregates such as bicelles provide useful isotropic or anisotropic membrane mimetics for structural studies of biological membranes. We have shown previously by deuterium NMR that a wedge-shaped amphiphilic derivative of trimethyl betacyclodextrin anchored in deuterated DMPC-d27 bilayers through a lauryl acyl chain (TrimbetaMLC) is able to induce magnetic orientation and fragmentation of the multilamellar membranes. The fragmentation process fully detailed in the present paper is observed with 20% cyclodextrin derivative below 37 degrees C, where pure TrimbetaMLC self-assembles in water into large giant micellar structures. After deconvolution of a broad composite (2)H NMR isotropic component, we propose a model where the DMPC membranes are progressively disrupted by TrimbetaMLC into small and large micellar aggregates depending whether they are extracted from the outer or inner layers of the liposomes. Below the fluid-to-gel transition of pure DMPC-d27 membranes (T(c) = 21.5 degrees C), the micellar aggregates vanish progressively until complete extinction at 13 degrees C, with a probable release of pure TrimbetaMLC micelles leaving lipid bilayers in the gel phase doped with only a small amount of the cyclodextrin derivative. Bilayer fragmentation between T(c) and 13 degrees C was also observed with 10% and 5% of TrimbetaMLC, with NMR spectra suggesting possible interactions of micellar aggregates with fluid-like lipids of the P(beta') ripple phase. No membrane orientation and fragmentation was detected with unsaturated POPC membranes, which are able to accommodate the insertion of TrimbetaMLC without important perturbation. The data are discussed in relation to the formation of possible DMPC bicellar aggregates such as those known to occur after insertion of dihexanoylphosphatidylcholine (DHPC). These bicelles are in particular associated with similar deuterium NMR spectra exhibiting identical composite isotropic components which were never characterized before.
https://dx.doi.org/10.1021/acs.jpcb.2c07331

Mass Spectrometry, Ion Mobility Separation and Molecular Modelling: A Powerful Combination for the Structural Characterisation of Substituted Cyclodextrins Mixtures
Rigaud, S.; Dosso, A.; Lesur, D.; Cailleu, D.; Mathiron, D.; Pilard, S.; Cezard, C.; Djedaini-Pilard, F.
Int J Mol Sci 2022, 23, 13352.
When working on the synthesis of substituted cyclodextrins (CDs), the main challenge remains the analysis of the reaction media content. Our objective in this study was to fully characterise a complex isomers mixture of Lipidyl-betaCDs (LipbetaCD) obtained with a degree of substitution 1 (DS = 1) from a one-step synthesis pathway. The benefit of tandem mass spectrometry (MS/MS) and ion mobility separation hyphenated with mass spectrometry (IM-MS) was investigated. The MS/MS fragment ion's relative intensities were analysed by principal component analysis (PCA) to discriminate isomers. The arrival time distribution (ATD) of each isomer was recorded using a travelling wave ion mobility (TWIM) cell allowing the determination of their respective experimental collision cross section (CCSexp). The comparison with the predicted theoretical CCS (CCSth) obtained from theoretical calculations propose a regioisomer assignment according to the betaCD hydroxyl position (2, 3, or 6) involved in the reaction. These results were validated by extensive NMR structural analyses of pure isomers combined with molecular dynamics simulations. This innovative approach seems to be a promising tool to elucidate complex isomer mixtures such as substituted cyclodextrin derivatives.
https://dx.doi.org/10.3390/ijms232113352

Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases
Kamal, R. M.; Abdull Razis, A. F.; Mohd Sukri, N. S.; Perimal, E. K.; Ahmad, H.; Patrick, R.; Djedaini-Pilard, F.; Mazzon, E.; Rigaud, S.
Molecules 2022, 27, 624.
Neurodegenerative diseases (NDDs) and cardiovascular diseases (CVDs) are illnesses that affect the nervous system and heart, all of which are vital to the human body. To maintain health of the human body, vegetable diets serve as a preventive approach and particularly Brassica vegetables have been associated with lower risks of chronic diseases, especially NDDs and CVDs. Interestingly, glucosinolates (GLs) and isothiocyanates (ITCs) are phytochemicals that are mostly found in the Cruciferae family and they have been largely documented as antioxidants contributing to both cardio- and neuroprotective effects. The hydrolytic breakdown of GLs into ITCs such as sulforaphane (SFN), phenylethyl ITC (PEITC), moringin (MG), erucin (ER), and allyl ITC (AITC) has been recognized to exert significant effects with regards to cardio- and neuroprotection. From past in vivo and/or in vitro studies, those phytochemicals have displayed the ability to mitigate the adverse effects of reactive oxidation species (ROS), inflammation, and apoptosis, which are the primary causes of CVDs and NDDs. This review focuses on the protective effects of those GL-derived ITCs, featuring their beneficial effects and the mechanisms behind those effects in CVDs and NDDs.
https://dx.doi.org/10.3390/molecules27030624

Cyclodextrin Complexation as a Way of Increasing the Aqueous Solublity and Staility of Carvedilol
Rigaud, S.; Mathiron, D.; Moufawad, T.; Landy, D.; Djedaini-Pilard, F.; Marçon, F.
Pharmaceutics 2021, 13, 1746.
We studied the effect of several CDs on carvedilol’s solubility and chemical stability in various aqueous media. Our present results show that it is possible to achieve a carvedilol concentration of 5 mg/mL (12.3 mM) in the presence of 5 eq of γCD or RAMEB in an aqueous medium with an acceptable acid pH (between 3.5 and 4.7). Carvedilol formed 1:1 inclusion complexes but those with RAMEB appear to be stronger (K = 317 M−1 at 298 K) than that with γCD (K = 225 M−1 at 298 K). The complexation of carvedilol by RAMEB significantly increased the drug’s photochemical stability in aqueous solution. These results might constitute a first step towards the development of a novel oral formulation of carvedilol.
https://dx.doi.org/10.3390/pharmaceutics13111746

First step to the improvement of the blood brain barrier passage of atazanavir encapsulated in sustainable bioorganic vesicles
Nolay, F.; Sevin, E.; Létévé, M.; Bil, A.; Gosselet, F.; El Kirat, K.; Djedaini-Pilard, F.; Morandat, S.; Fenart, L.; Przybylski, C.; Bonnet, V.
Int. J. Pharm. 2020, 587, 119604.
The blood - brain barrier (BBB) prevents the majority of therapeutic drugs from reaching the brain following intravenous or oral administration. In this context, polymer nanoparticles are a promising alternative to bypass the BBB and carry drugs to brain cells. Amphiphilic cyclodextrins can form self-assemblies whose nanoparticles have a 100-nm-diameter range and are thus able to encapsulate drugs for controlled release. Our goal is to propose an optimized chemical synthesis of amphiphilic cyclodextrin, which remains a challenging task which commonly leads to only a low-milligram level of the high purity compound. Such cyclodextrin derivatives were used to prepare vesicles and to study their ability to vectorize a drug through the BBB. As a result, we introduced a convergent synthesis for a family of lipophosphoramidyl permethylated β-CDs (Lip-β-CDs) with various chain lengths. It was demonstrated that mixed vesicles comprised of phosphatidylcholine (POPC) and LipCDs were able to encapsulate atazanavir (ATV), a well-known protease inhibitor used as an antiretroviral drug against HIV. We highlighted that neo-vesicles promote the penetration of ATV in endothelial cells of the BBB, presumably due to the low fusogenicity of Lip-β-CDs.
https://dx.doi.org/10.1016/j.ijpharm.2020.119604

New Lipidyl-Cyclodextrins Obtained by Ring Opening of Methyl Oleate Epoxide Using Ball Milling
Oliva, E.; Mathiron, D.; Rigaud, S.; Monflier, E.; Sevin, E.; Bricout, H.; Tilloy, S.; Gosselet, F.; Fenart, L.; Bonnet, V.; Pilard, S.; Djedaini-Pilard, F.
Biomolecules 2020, 10, 339.
Bearing grafts based on fatty esters derivatives, lipidyl-cyclodextrins (L-CDs) are compounds able to form water-soluble nano-objects. In this context, bicatenary biobased lipidic-cyclodextrins of low DS were easily synthesized from a fatty ester epoxide by means of alternative methods (ball-milling conditions, use of enzymes). The ring opening reaction of methyl oleate epoxide needs ball-milling and is highly specific of cyclodextrins in solventless conditions. L-CDs are thus composed of complex mixtures that were deciphered by an extensive structural analysis using mainly mass spectrometry and NMR spectroscopy. In addition, as part of their potential use as vectors of active drugs, these products were submitted to an integrity study on in vitro model of the blood-brain-barrier (BBB) and the intestinal epithelium. No toxicity has been observed, suggesting that applications for the vectorization of active ingredients can be expected.
https://dx.doi.org/10.3390/biom10020339

Rhodium-Catalyzed Aqueous Biphasic Olefin Hydroformylation Promoted by Amphiphilic Cyclodextrins
Cocq, A.; Bricout, H.; Djedaïni-Pilard, F.; Tilloy, S.; Monflier, E.
Catalysts 2020, 10, 56.
Hydroformylation is an industrial process that allows for the production of aldehydes from alkenes using transition metals. The reaction can be carried out in water, and the catalyst may be recycled at the end of the reaction. The industrial application of rhodium-catalyzed aqueous hydroformylation has been demonstrated for smaller olefins (propene and butene). Unfortunately, larger olefins are weakly soluble in water, which results in very low catalytic activity. In an attempt to counteract this, we investigated the use of amphiphilic oleic succinyl-cyclodextrins (OS-CDs) synthesized from oleic acid derivatives and maleic anhydride. OS-CDs were found to increase the catalytic activity of rhodium during the hydroformylation of water-insoluble olefins, such as 1-decene and 1-hexadecene, by promoting mass transfer. Recyclability of the catalytic system was also evaluated in the presence of these cyclodextrins.
https://dx.doi.org/10.3390/catal10010056

Anionic Amphiphilic Cyclodextrins bearing Oleic Grafts for the Stabilization of Ruthenium Nanoparticles Efficient in Aqueous Catalytic Hydrogenation
Cocq, A.; Leger, B.; Noel, S.; Bricout, H.; Pilard, F.; Tilloy, S.; Monflier, E.
ChemCatChem 2019, n/a.
Oleic succinyl β-cyclodextrin was proved to be efficient for the stabilization of ruthenium nanoparticles (NPs) in aqueous medium. These NPs were characterized by FTIR spectroscopy and transition electron microscopy (TEM). The catalytic activity of these NPs was evaluated in the aqueous hydrogenation of petrosourced and biosourced unsaturated compounds such as benzene and furfural derivatives. The catalytic system can be easily recycled and reused up to nine runs without any loss of activity and selectivity, demonstrating its robustness.
https://dx.doi.org/10.1002/cctc.201901837

Comparative binding and uptake of liposomes decorated with mannose oligosaccharides by cells expressing the mannose receptor or DC-SIGN
Gao, H.; Gonçalves, C.; Gallego, T.; François-Heude, M.; Malard, V.; Mateo, V.; Lemoine, F.; Cendret, V.; Djedaini-Pilard, F.; Moreau, V.; Pichon, C.; Midoux, P.
Carbohydr. Res. 2020, 487, 107877.
Mannose Receptor (MR) and DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) are two mannose-specific targets for antigens carried by liposomes but DC-SIGN is more specific of DCs. Here, DC targeting is addressed by using DPPC/DOPE liposomes decorated with a series of diether lipids with a polar head of either a mannose (Man), tri-antenna of α-d-mannopyranoside (Tri-Man), [Manα1-3(Manα1-6)Man] (Man-tri), pseudo-Man4 (PMan4) or pseudo-Man5 (PMan5). Liposomes decorated with Man-Tri show the highest binding and internalization in cells expressing DC-SIGN and in human monocytes-derived DCs. Conversely, cells expressing MR bind and take up Tri-Man liposomes 3-fold higher than Man-tri liposomes. Comparatively, liposomes decorated with PMan4 and PMan5 do not show any advantages. Overall, the results indicate that liposomes decorated with Man-tri residues are more selective toward DCs than those with Tri-Man thanks to better recognition by DC-SIGN.
https://doi.org/10.1016/j.carres.2019.107877

Ordering of Saturated and Unsaturated Lipid Membranes near Their Phase Transitions Induced by an Amphiphilic Cyclodextrin and Cholesterol
Roux, M.; Bonnet, V.; Djedaïni-Pilard, F.
Langmuir 2019.
When inserted in membranes of dimyristoyl phosphatidylcholine (DMPC), methylated β-cyclodextrins with one (TrimβMLC) or two (TrimβDLC) lauryl acyl chains grafted onto the hydrophilic cavity exert a “cholesterol-like ordering effect”, by straightening the acyl chains in the fluid phase at temperatures near the chain melting transition. This effect may be related to pretransitional events such as the “anomalous swelling” known to occur with saturated phosphatidylcholine membranes. To investigate this model, order profiles and bilayer thicknesses of DMPC and unsaturated 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) membranes containing amphiphilic cyclodextrins or cholesterol were determined by deuterium NMR. The pure lipid membranes display both a qualitatively similar chain ordering upon cooling in the fluid phase, more important at the chain extremity, which gets more pronounced near their fluid-to-gel transitions. Both membranes show a bilayer thickness increase by ∼0.5 Å just above their transition, as observed previously with saturated phosphatidylcholines of various chain lengths. Membrane-insertion of 5% TrimβMLC or cholesterol induces an important ordering of the DMPC acyl chains just above the transition, which is also more pronounced at the chain extremity. There is an additional increase of the bilayer thickness, most probably due to a deep insertion of these amphiphilic molecules, facilitated by increased bilayer softness in the anomalous swelling regime. These effects are more important with TrimβMLC than with cholesterol. By contrast, no enhanced acyl chain ordering was observed when approaching the transition of TrimβMLC-containing POPC membranes, as a possible consequence of an eventual lack of anomalous swelling in unsaturated lipid membranes. Insertion of higher concentrations of TrimβMLC was found to induce a magnetic orientation of the DMPC membranes in the fluid phase with 10% of this derivative, coupled with the appearance of a broad isotropic component when the concentration is raised to 20%. No membrane orientation or isotropic component was detected with TrimβMLC-containing POPC membranes.
https://dx.doi.org/10.1021/acs.langmuir.9b02082

Highly Water-Soluble Amphiphilic Cyclodextrins Bearing Branched and Cyclic Oleic Grafts
Cocq, A.; Rousseau, C.; Bricout, H.; Oliva, E.; Bonnet, V.; Djedaïni-Pilard, F.; Monflier, E.; Tilloy, S.
Eur. J. Org. Chem.
Amphiphilic β-cyclodextrins bearing various amounts of branched and cyclic oleic grafts are synthetized. The first step of this synthesis is the alkenylation of maleic anhydride by oleic acid derivatives, in the presence of a rhodium catalyst, to produce oleic succinic anhydrides with different ratios of cyclic to branched groups. The second step is the grafting of the oleic succinic anhydrides mixtures on β-cyclodextrin. The obtained cyclodextrins are highly water-soluble and surface active.
https://dx.doi.org/10.1002/ejoc.201900789

Oleic Acid Based Cyclodextrins for the Development of New Hydrosoluble Amphiphilic Compounds
Cocq, A.; Rousseau, C.; Bricout, H.; Oliva, E.; Bonnet, V.; Djedaïni-Pilard, F.; Monflier, E.; Tilloy, S.
Eur. J. Org. Chem. 0.
A new family of amphiphilic cyclodextrins produced from oleic acid derivatives and maleic anhydride is described. These amphiphilic cyclodextrins are synthesized in two steps. The first step is the alkenylation of maleic anhydride by oleic acid derivatives to produce the oleic succinic anhydrides. The second step is the grafting of the oleic succinic anhydrides on various cyclodextrins. A self-inclusion of the alkyl chain or an inclusion of one alkyl chain in the cavity of another CD is showed by NMR experiments. The twelve amphiphilic cyclodextrins described possess high solubility in water (50–500 g/L at 20 °C) and low critical aggregation concentration (16–360 mg/L).
http://dx.doi.org/10.1002/ejoc.201801609

An air-stable lithiated cathode material based on a 1,4-benzenedisulfonate backbone for organic Li-ion batteries
Lakraychi, A. E.; Deunf, E.; Fahsi, K.; Jimenez, P.; Bonnet, J. P.; Djedaini-Pilard, F.; Bécuwe, M.; Poizot, P.; Dolhem, F.
Journal of Materials Chemistry A 2018.
To meet current market demands as well as emerging environmental concerns there is a need to develop less polluting battery technologies. Organic electrode materials could offer the possibility of preparing electrode materials from naturally more abundant elements and eco-friendly processes coupled with simplified recycling management. However, the potential use of organic electrode materials for energy storage is still challenging and a lot of developments remain to be achieved. For instance, promoting high-energy Li-ion organic batteries inevitably requires the development of lithiated organic electrode materials which are able to be charged (delithiated) at a high enough potential (>3 V vs. Li+/Li0) – a challenging point rarely discussed in the literature. Here, we evaluate tetralithium 2,5-dihydroxy-1,4-benzenedisulfonate as an air-stable lithiated cathode material for the first time and its reversible Li+ electrochemical extraction. Quite interestingly, in comparison with the dicarboxylate counterpart, it was observed that the theoretical two-electron reaction is readily reached with this organic structure and at an average operating potential of 650 mV higher.
http://dx.doi.org/10.1039/c8ta07097k

Physico-chemical studies of resveratrol, methyl-jasmonate and cyclodextrin interactions: an approach to resveratrol bioproduction optimization
Oliva, E.; Mathiron, D.; Bertaut, E.; Landy, D.; Cailleu, D.; Pilard, S.; Clément, C.; Courot, E.; Bonnet, V.; Djedaïni-Pilard, F.
RSC Advances 2018, 8, 1528-1538.
trans-Resveratrol (RSV) is a natural phenolic molecule of the stilbene family known for its anti-oxidant properties in the field of nutraceuticals and cosmetics. Its production by grapevine cell suspensions is induced by the addition to the culture medium of elicitor compounds, methyl jasmonate (MeJA) and cyclodextrins (CDs). Physico-chemical studies were performed to understand the mechanism of action of CDs on this bioproduction of RSV. Inclusion complexes of RSV in CDs were first observed and then interactions with MeJA were identified using various analytical techniques such as UV and nuclear magnetic resonance (NMR) spectroscopies, mass spectrometry (MS) and isothermal titration calorimetry (ITC).
http://dx.doi.org/10.1039/c7ra11619e

Decreasing redox voltage of terephthalate-based electrode material for Li-ion battery using substituent effect
Lakraychi, A. E.; Dolhem, F.; Djedaïni-Pilard, F.; Thiam, A.; Frayret, C.; Becuwe, M.
J. Power Sources 2017, 359, 198-204.
The preparation and assessment versus lithium of a functionalized terephthalate-based as a potential new negative electrode material for Li-ion battery is presented. Inspired from molecular modelling, a decrease in redox potential is achieved through the symmetrical adjunction of electron-donating fragments (–CH3) on the aromatic ring. While the electrochemical activity of this organic material was maximized when used as nanocomposite and without any binder, the potential is furthermore lowered by 110 mV upon functionalization, consistently with predicted value gained from DFT calculations.
http://dx.doi.org/https://doi.org/10.1016/j.jpowsour.2017.05.046

Synthesis of high-mannose oligosaccharide analogues through click chemistry: true functional mimics of their natural counterparts against lectins?
Francois-Heude, M.; Mendez-Ardoy, A.; Cendret, V.; Lafite, P.; Daniellou, R.; Ortiz Mellet, C.; Garcia Fernandez, J. M.; Moreau, V.; Djedaini-Pilard, F.
Chemistry 2015, 21, 1978-91.
Terminal "high-mannose oligosaccharides" are involved in a broad range of biological and pathological processes, from sperm-egg fusion to influenza and human immunodeficiency virus infections. In spite of many efforts, their synthesis continues to be very challenging and actually represents a major bottleneck in the field. Whereas multivalent presentation of mannopyranosyl motifs onto a variety of scaffolds has proven to be a successful way to interfere in recognition processes involving high-mannose oligosaccharides, such constructs fail at reproducing the subtle differences in affinity towards the variety of protein receptors (lectins) and antibodies susceptible to binding to the natural ligands. Here we report a family of functional high-mannose oligosaccharide mimics that reproduce not only the terminal mannopyranosyl display, but also the core structure and the branching pattern, by replacing some inner mannopyranosyl units with triazole rings. Such molecular design can be implemented by exploiting "click" ligation strategies, resulting in a substantial reduction of synthetic cost. The binding affinities of the new "click" high-mannose oligosaccharide mimics towards two mannose specific lectins, namely the plant lectin concanavalin A (ConA) and the human macrophage mannose receptor (rhMMR), have been studied by enzyme-linked lectin assays and found to follow identical trends to those observed for the natural oligosaccharide counterparts. Calorimetric determinations against ConA, and X-ray structural data support the conclusion that these compounds are not just another family of multivalent mannosides, but real "structural mimics" of the high-mannose oligosaccharides.
http://dx.doi.org/10.1002/chem.201405481

Cyclodextrin nanoassemblies: a promising tool for drug delivery
Bonnet, V.; Gervaise, C.; Djedaïni-Pilard, F.; Furlan, A.; Sarazin, C.
Drug Discovery Today 2015, 20, 1120-1126.
Among the biodegradable and nontoxic compounds that can form nanoparticles for drug delivery, amphiphilic cyclodextrins are very promising. Apart from ionic cyclodextrins, which have been extensively studied and reviewed because of their application in gene delivery, our purpose is to provide a clear description of the supramolecular assemblies of nonionic amphiphilic cyclodextrins, which can form nanoassemblies for controlled drug release. Moreover, we focus on the relationship between their structure and physicochemical characteristics, which is crucial for self assembly and drug delivery. We also highlight the importance of the nanoparticle technology preparation for the stability and application of this nanodevice.
http://dx.doi.org/10.1016/j.drudis.2015.05.008

A green approach to the synthesis of novel phytosphingolipidyl β-cyclodextrin designed to interact with membranes
Miao, Y.; Djedaini-Pilard, F.; Bonnet, V.
Beilstein J. Org. Chem. 2014, 10, 2654-2657, 4 pp.
This work reports the synthesis of a new family of mono-substituted amphiphilic cyclodextrins using a green methodol. Reactions using greener and safer catalysts with more environmentally friendly purifn. solvents were performed. Four unreported mono-substituted cyclodextrins bearing a phytosphingolipidyl chain and a fatty acid chain (C10, C12, C14 and C18) were successfully obtained with a promising yield.
http://dx.doi.org/10.3762/bjoc.10.278

The synthesis of a glucoconjugate of the peptidic fragment of cryptophycin-24
Mezrai, A.; Lesur, D.; Wadouachi, A.; Pilard, F.; Mulengi, J. K.
Mediterranean Journal of Chemistry 2014, 3, 935-946.
A novel glucoconjugate of the peptidic fragment of cryptophycin-24 was prepd. through the replacement of the leucic acid residue with L-leucine and the functionalisation of tyrosine residue with glucose. Those modifications lead to a novel protected tripeptide fragment of cryptophycin-24.
http://dx.doi.org/10.13171/mjc.3.4.2014.04.07.15

The Synthesis of an Aziridinyl Analogue of Unit A of Cryptophycin-1
Mezrai, A.; Drici, W.; Lesur, D.; Mulengi, J.; Wadouachi, A.; Pilard, F.
Lett. Org. Chem. 2014, 11, 259-267.
A novel analog of unit A of cryptophycin-1 was prepd. starting from com. trans-cinnamaldehyde. The modifications introduced into the new structure related to the replacement of the epoxide with an aziridine moiety, and the inclusion of the 1,3-enone moiety into an arom. ester frame through the synthesis of a key arom. ketone. Asymmetry was induced during the later steps of the synthetic pathway. The optical purity of compds. was monitored by chiral HPLC and polarimetric measurements.
http://dx.doi.org/10.2174/1570178611999140221163917

Diesterification of 3-[(β-Cyclodextrinyl)succinamido]propane-1,2-diol Catalysed by Lipase: Diastereoselectivity or Tridimensional Substrate Specificity?
Gervaise, C.; Bonnet, V.; Nolay, F.; Cezard, C.; Stasik, I.; Sarazin, C.; Djedaini-Pilard, F.
Eur. J. Org. Chem. 2014, 2014, 6200-6209.
The transesterification of 3-[(β-cyclodextrinyl)succinamido]propane-1,2-diol with fatty esters catalyzed by immobilized lipase from Mucor miehei occurred with very different conversions of the two diastereoisomers [(R)- or (S)-amidopropanediol]. The highest conversion obsd. with the (S)-amidopropanediol can be related to either lipase diastereoselectivity or substrate specificity. To investigate the diastereoselectivity of the lipase, diastereoisomers of the methylated β-cyclodextrin were replaced by methylated glucopyranoside or methylleucine. No discrimination of the diastereoisomers by lipase was obsd. Mol. modeling was performed to assess the lipase selectivity towards the two diastereoisomers. It was found that the (R)-amidopropanediol is stabilized by hydrogen bonding with the cyclodextrin rim resulting in less reactive hydroxy groups.
http://dx.doi.org/10.1002/ejoc.201402414

5-O-caffeoylshikimic acid from Solanum somalense leaves: advantage of centrifugal partition chromatography over conventional column chromatography
Chideh, S.; Pilard, S.; Attoumbre, J.; Saguez, R.; Hassan-Abdallah, A.; Cailleu, D.; Wadouachi, A.; Baltora-Rosset, S.
J. Sep. Sci. 2014, 37, 2331-9.
Solanum somalense leaves, used in Djibouti for their medicinal properties, were extracted by MeOH. Because of the high polyphenol and flavonoid contents of the extract, respectively, determined at 80.80 +/- 2.13 mg gallic acid equivalent/g dry weight and 24.4 +/- 1.01 mg quercetin equivalent/g dry weight, the isolation and purification of the main polyphenols were carried out by silica gel column chromatography and centrifugal partition chromatography. Column chromatography led to 11 enriched fractions requiring further purification, while centrifugal partition chromatography allowed the easy recovery of the main compound of the extract. In a solvent system composed of CHCl3/MeOH/H2O (9.5:10:5), 21.8 mg of this compound at 97% purity was obtained leading to a yield of 2.63%. Its structure was established as 5-O-caffeoylshikimic acid by mass spectrometry and NMR spectroscopy. This work shows that S. somalense leaves contain very high level of 5-O-caffeoylshikimic acid (0.74% dry weight), making it a potential source of production of this secondary metabolite that is not commonly found in nature but could be partly responsible of the medicinal properties of S. somalense leaves.
http://dx.doi.org/10.1002/jssc.201400226