The multivalent effect in glycosidase inhibition: probing the influence of architectural parameters with cyclodextrin-based iminosugar click clusters

In contrast to most lectins, glycosidases may appear to be unpromising targets for multivalent binding because they display only a single active site. To explore the potential of multivalency on glycosidase inhibition, unprecedented cyclodextrin-based iminosugar conjugates have been designed and prepared. The synthesis was performed by way of Cu(I) -catalyzed azide-alkyne cycloaddition reaction under microwave activation between propargylated multivalent β-cyclodextrins and an azide-armed N-alkyl 1-deoxynojirimycin derivative. Evaluation with a panel of glycosidases of this new class of glycomimetic clusters revealed the strongest affinity enhancement observed to date for a multivalent glycosidase inhibitor, with binding enhancement up to four orders of magnitude over the corresponding monovalent ligand for α-mannosidase. These results demonstrate that the multivalency concept extends beyond carbohydrate-lectin recognition processes to glycomimetic-enzyme inhibition.     

Suspension polymerization of thermotropic monomer: Formation of droplets or beads

Ordered beads were obtained by the suspension copolymerization of amesogenic methacrylate-based monomer and methacrylic acid. The stability of these particles and the liquid crystal organization inside the particles depend mainly on the time of polymerization and on the crosslinking. Suspended droplets of monomers or polymers can be obtained as well as solid spheres. The solid particles exhibit ordered microstructures with a liquid crystal configuration that has a variable form depending on polymerization time and observation temperature. Bead characteristics such as morphology, size and polydispersity, and porosity are discussed and compared with those of non-mesomorphic beads. The mesomorphic beads are smaller and their porosity lower. The presence of a crosslinker during the polymerization process leads to more mechanically stable particles with retention of polymorphism.     

Aldolic Condensations on Inorganic Solid Support: Application to the Synthesis of O-Ethyl Esters of 3-Phenyl-2-propenethioic Acids

Aldolic condensations with 0-ethyl thioesters are performed on basic alumina to give 2,3-unsaturated thioates. The stereochemistry of the reaction is discussed and compared with Knoevenagel's, Pinner's and Wittig-Horner's reactions.     

Natural neighbor coordinates of points on a surface

Natural neighbor coordinates and natural neighbor interpolation have been introduced by Sibson for interpolating multivariate scattered data. In this paper, we consider the case where the data points belong to a smooth surface , i.e., a (d−1)-manifold of . We show that the natural neighbor coordinates of a point X belonging to tends to behave as a local system of coordinates on the surface when the density of points increases. Our result does not assume any knowledge about the ordering, connectivity or topology of the data points or of the surface. An important ingredient in our proof is the fact that a subset of the vertices of the Voronoi diagram of the data points converges towards the medial axis of when the sampling density increases.     

Synthesis of spirocyclopropyl γ-lactams by tandem intramolecular azetidine ring-opening/closing cascade reaction: synthetic and mechanistic aspects

The scope and limitations of a novel intramolecular azetidine ring-opening/closing cascade reaction affording spirocyclopropyl γ-lactams from azetidines in high regio- and stereoselectivity is reported. The key step of the process is a S_N2-type ring-opening of TMSOTf-activated azetidine rings by silyl ketene acetals generated by treatment with TMSOTf and TEA. This study is a very rare example of nucleophilic ring-opening of azetidines that does not require formation of quaternary azetidinium salts by N-alkylation or the use of N-electron-withdrawing groups. Application of this process to 2-azetidinone system led to a complete change in reactivity and provide 6-aza-bicyclo[3.2.0]heptane derivatives via an unprecedented Mukaiyama aldol-like reaction involving an ester acceptor and a silyl imidate.     

Delaunay Triangulation of Manifolds

We present an algorithm for producing Delaunay triangulations of manifolds. The algorithm can accommodate abstract manifolds that are not presented as submanifolds of Euclidean space. Given a set of sample points and an atlas on a compact manifold, a manifold Delaunay complex is produced for a perturbed point set provided the transition functions are bi-Lipschitz with a constant close to 1, and the original sample points meet a local density requirement; no smoothness assumptions are required. If the transition functions are smooth, the output is a triangulation of the manifold. The output complex is naturally endowed with a piecewise-flat metric which, when the original manifold is Riemannian, is a close approximation of the original Riemannian metric. In this case the output complex is also a Delaunay triangulation of its vertices with respect to this piecewise-flat metric.     

O-ethyl thiocarbamates. A convenient route to 2-aryliminoimidazolidines

The reaction of N-aryl thionocarbamates and ethylenediamine lead to the corresponding 2-arylimino-imidazolidines, whose structure in pharmacology is well known. But, the behaviour of the N-alkyl thionocarbamates is quite different under operative conditions and these compounds afford with ethylenediamine, to 2-(2′-aminoethylamino)-Δ²-imidazoline, according to a mechanism which is discussed.     

Synthesis and biological evaluation of the first example of an eight-membered iminoalditol

The synthesis of the first examples of eight-membered iminoalditols has been achieved from 2,3,4,6-tetra-O-benzyl-d-glucopyranose by way of a ring-closing metathesis. The (2R,3R,4R,5S)-2-hydroxymethyl-azocane-3,4,5-triol (3a), which has the d-gluco configuration for C-2-C-5 and appears to exist predominantly in a boat-chair conformation, is a weak inhibitor of glycosidases.     

Platinum oxide catalyzed hydrosilylation of unsymmetrical internal aryl alkynes under ortho-substituent regiocontrol

[chemical reaction: see text]. PtO2- and H2PtCl6-catalyzed hydrosilylation of internal aryl alkynes having a para or an ortho substituent with triethylsilane are discussed and compared. The regioselectivity of the H-Si bond addition was found to be controlled by the ortho substituent rather than the nature of the platinum catalyst. Arylalkynes with an ortho substituent, regardless of its electronic nature, directed the silyl substituent mainly to the alpha-position. PtO2 proved to be a versatile and powerful catalyst compared to H2PtCl6 since it prevents the alkyne reduction.     

One-pot hydrosilylation-protodesilylation of functionalized diarylalkynes: a highly selective access to Z-stilbenes. Application to the synthesis of combretastatin A-4

An efficient stereoselective synthesis of Z-stilbenes has been developed from diarylalkynes via a new hydrosilylation-protodesilylation process. The scope and limitation of this method is presented to stereoselectively prepare a wide range of (Z)-stilbenes in a one-pot way is presented. A concise application to the preparation of combretastatin A-4 (CA-4), a vascular targeting agent inhibitor of tubulin polymerisation is described.