Soledad Penadés

Nanoparticles as Nonviral Gene Delivery Vectors

Gene therapy, as therapeutic treatment to genetic or acquired diseases, is attracting much interest in the research community, leading to noteworthy developments over the past two decades. Although this field is still dominated by viral vectors, nonviral vectors have recently received an ever increasing attention in order to overcome the safety problems of their viral counterpart. This review presents the biological aspects involved in the gene delivery process and explores the recent developments and achievements of nonviral gene carriers.

Carbohydrate-Carbohydrate Interactions in Biological and Model Systems

Carbohydrate-carbohydrate interactions are emerging as a novel and versatile mechanism for cell adhesion and recognition. Although this interaction has not deserved much attention of cell biologists, biochemists, or carbohydrate chemists, new evidence and studies are confirming the importance of this mechanism for specific cell adhesion and communication. The study and evaluation of carbohydrate-carbohydrate interactions is still in its infancy. Their development will go hand in hand with the development of new and more sensitive techniques to study weak interactions such as biosensors, atomic force microscopy, or weak affinity chromatography. In this contribution we will review these new emerging carbohydrate-carbohydrate related interactions including those already established and those where the carbohydrate involvement, at this moment, may be considered possible as in the case of DNA-carbohydrate interaction. The two main research lines on carbohydrate-carbohydrate interaction in biological systems and the efforts, using model systems, to demonstrate and evaluate these interactions are reviewed here in some detail. Considerations about the intermolecular forces and the mechanism that may be involved in carbohydrate-carbohydrate interactions are also presented. The chapter ends with the review of the few examples existing in the literature on quantitative studies of carbohydrate-carbohydrate interaction with model systems.

Synthesis, complexing properties and applications in asymmetric synthesis of bis-lacto-18-crown-6 compounds

Abstract The new chiral bis- lacto -18-crown-6 derivatives 1 and 2 have been synthesized in a straightforward and easy way from benzyl β-lactoside.The complexing properties of 1, 2, and the previously synthesized mono- lacto -crown-6 compounds 3–6 have been evaluated by different methods. Compounds 1 and 2 complexed to potassium tert-butoxide have been used as catalysts in the addition, of phenylacetate to methyl acrylate to give the corresponding Michael adduct with reasonable enantiomeric excesses.

Asymmetric Michael reaction using macrocyclic lactose derivatives as chiral catalysts.

Abstract Macrocyclic lactose derivatives complexed to potassium bases catalysed the Michael addition of phenyl- and naphthylacetic esters to methyl acrylate to give the corresponding adducts in enantiomeric excess ranging from 20 to 70%.

Carbohydrate–Arene Interactions Direct Conformational Equilibrium of a Flexible Glycophane in Water

Water, the flexibility of the maltose molecule, and sugar/arene interactions are responsible for the equilibrium between a folded (I) and nonfolded (II) conformation in a glycophane (III is an intermediate). Glycophanes are cyclodextrin-cyclophane hybrids, which are of interest as models of receptors.

The regioselective synthesis of enantiomerically pure myo-inositol derivatives. Efficient synthesis of myo-inositol 1,4,5-trisphosphate.

Abstract Regioselective 1- O -acylation of myo -inositol and simultaneous optical resolution has been achieved by perborylation, transmetallation using di- n -butyltin-bis-acetylacetonate and then acylation with (−)-menthyl chloroformate. Diastereomerically pure 1- O -(−)-menthoxycarbonyl- myo -inositol 1 can be used as starting material for the preparation of biologically important myo -inositol phosphates and glycosyl phosphatidylinositols in a shorter and effective way.

Chiral macrocyclic compounds from lactose derivatives

Abstract The reaction of benzyl 2,6,6′-tri- O -benzyl-3′,4′- O -isopropylidene-β-lactoside with 1,11-ditosyloxy-3,6,9-trioxaundecane gave benzyl 2,6,6′-tri- O -benzyl-3′,4′- O -isopropylidene-3,2′- O --(3,6,9-trioxaundecane-1,11-diyl)-β-lactoside ( 2 , 47%). Acid hydrolysis of 2 and condensation of the product with 1,14-ditosyloxy-3,6,9,12-tetra-oxatetradecane afforded benzyl 2,6,6′-tri- O -benzyl-3′,4′- O -(3,6,9,12-tetraoxa-tetradecane-1,14-diyl)-3,2′- O -(3,6,9-trioxaundecane-1,11-diyl)-β-lactoside (29%). Similarly, the reaction of benzyl 2,6,2′,4′,6′-penta- O -benzyl-β-lactoside with Ts[OCH 2 CH 2 ] 4 OTs gave benzyl 2,6,2′,4′,6′-penta- O -benzyl-3,3′- O -(3,6,9-trioxaundecane-1,11-diyl)-β-lactoside (78%). 1 H-N.m.r. spectroscopy has been used to study the formation of host-guest complexes with some of these macrocyclic compounds and benzyl ammonium thiocyanate.

New synthetic strategy to highly symmetric chiral macrocycles from carbohydrate derivatives

Abstract A simple strategy for the synthesis of highly symmetric macrocycles incorporating carbohydrates is presented. The application of this strategy to the synthesis of optically active tetra-gluco-24-crown-8 (1), bis-gluco-15-crown-5 (3), and bis-gluco-21-crown-8 (5) is described. Preliminary studies showed that macrocycles 1, 3 and 5 complex ammonium salts. These macrocyclic compounds have been used as catalysts in the asymmetric Michael addition of methyl α-phenylacetate to methyl acrylate.

Synthesis, NMR, and preliminary binding studies of a new chiral macrocycle from β-cyclodextrin

Abstract The reduction of per-O-diethylboryl β-cyclodextrin with ethyl-diborane in the presence of 9-bora-bicyclo 3.3.1 non-9-yl-mesylate afforded, after deboronation and acetylation, the 1,5-anhydro-D-glucitol derivative 4 (60%) and the new macrocyclic polyhydroxyether 3 (30%). The 1H and 13C n.m.r. spectra of 3 and the deacetylated derivative 1 have been studied. The 13C T1 values for 3 and 1 indicated a higher degree of internal motion in comparison to β-cyclodextrin. The binding ability of 3 has been investigated using Crams picrate method.

New Chiral Macrocyclic Compounds from D-Mannitol

Abstract We have recently reported the synthesis of new chiral macrocyclic polyhydroxyethers by reduction of cyclodextrins 1. These compounds display appreciable conformational freedom in solution as it occurs with the ionophores. Our chiral macrocycles may be considered as built by units of alditol (1 → 4) alditols. Such units, conveniently substituted, prepared by us by reduction of disaccharide derivatives2, are possible synthons for the synthesis of other macrocyclic polyhydroxyethers in which the nature and number of alditol (1 → n) alditol components can be varied at will. We are interested in the preparation and the structural studies of these type of receptors since the synthesis of new chiral macrocycles is a topic of interest and the building of chiral cavities may be of importance in the study of host-guest interactions. We now report on the preparation, from D-mannitol, a readily available starting material with C2symmetry, and tetraethylene glycol, of the chiral macrocycles 1, 2, and 3, as mo...