[Show abstract][Hide abstract] ABSTRACT: Dual promiscuous racemization/amidation activities of lipases leading to efficient dynamic kinetic resolution protocols of racemic α-aminonitrile compounds are described. α-Amidonitrile products of high enantiomeric purity could be formed in high yields. Several lipases from different sources were shown to exhibit the dual catalytic activities, where opposite enantioselectivities could be recorded for certain substrates.
[Show abstract][Hide abstract] ABSTRACT: A domino addition-lactonization pathway has been applied to a dynamic covalent resolution protocol, leading to efficient oxathiazinanone formation as well as chiral discrimination. A new, double biocatalytic pathway has furthermore been proposed and evaluated where the initial product inhibition could be efficiently circumvented.
[Show abstract][Hide abstract] ABSTRACT: A carbohydrate-anion recognition system in nonpolar solvents is reported, in which complexes form at the B-faces of β-D-pyranosides with H1-, H3-, and H5-cis patterns similar to carbohydrate-π interactions. The complexation effect was evaluated for a range of carbohydrate structures; it resulted in either 1:1 carbohydrate-anion complexes, or 1:2 complex formation depending on the protection pattern of the carbohydrate. The interaction was also evaluated with different anions and solvents. In both cases it resulted in significant binding differences. The results indicate that complexation originates from van der Waals interactions or weak CH⋅⋅⋅A(-) hydrogen bonds between the binding partners and is related to electron-withdrawing groups of the carbohydrates as well as increased hydrogen-bond-accepting capability of the anions.
Chemistry - An Asian Journal 03/2014; · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A dynamic azomethine ylide system was established using Sc(OTf)3 and Ag/Taniaphos as catalysts. The system was subsequently kinetically resolved in a tandem 1,3-dipolar cycloaddition process where the silver complex acted as both a reaction catalyst and an external selector, resulting in the formation of an exclusive pyrrolidine product in good yield and enantiopurity.
Chemical Communications 02/2014; · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A complex dynamic system based on a network of multiple reversible reactions has been established. The network was applied to a dynamic systemic resolution protocol based on kinetically controlled lipase-catalyzed transformations. This resulted in the formation of cyclized products, where two thiazolidinone compounds were efficiently produced from a range of potential transformations.
[Show abstract][Hide abstract] ABSTRACT: The anti-HIV nucleoside lamivudine was asymmetrically synthesized in only three steps via a novel surfactant-treated subtilisin Carlsberg-catalyzed dynamic kinetic resolution protocol. The enantiomer of lamivudine could also be accessed using the same protocol catalyzed by Candida antarctica lipase B.
Chemical Communications 09/2013; · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new microarray platform, based on lectin super-microarrays and glycans labeled with dye-doped nanoparticles, has been developed to study glycan-lectin interactions. Glycan ligands were conjugated onto fluorescein-doped silica nanoparticles (FSNPs) using a general photocoupling chemistry to afford FSNP-labeled glycan probes. Lectins were printed on epoxy slides in duplicate sets to generate lectin super-microarrays where multiple assays could be carried out simultaneously in each lectin microarray. Thus, the lectin super-microarray was treated with FSNP-labeled glycans to screen for specific binding pairs. Furthermore, a series of ligand competition assays were carried out on a single lectin super-microarray to generate the dose-response curve for each glycan-lectin pair, from which the apparent affinity constants were obtained. Results showed 4-7 orders of magnitude increase in affinity over the free glycans with the corresponding lectins. Thus, the glycan epitope structures having weaker affinity than the parent glycans could be readily identified and analyzed from the lectin super-microarrays.
[Show abstract][Hide abstract] ABSTRACT: A dynamic multicomponent reaction concept has been successfully applied to the syntheses of 3-thioisoindolinones and tricyclic γ-lactams. The reactions were efficiently designed and operated in the absence of any catalyst under mild reaction conditions, resulting in the convenient variation of substituents on the N- and S-positions of the target products.
Israel Journal of Chemistry (Online) 02/2013; 53(1‐2). · 2.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dynamic systems based on double parallel reactions have been generated and resolved in situ by secondary lipase-catalyzed asymmetric transformation, resulting in high chemo- and enantioselectivities.
Chemical Communications 01/2013; · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In previous studies, it was reported that a neighbouring equatorial ester group is essential for a good yield of nitrite-mediated triflate inversion, whereas with neighbouring benzyl ether groups or axial ester groups, mixtures are generally produced. In the present study, the origin of this difference was addressed. The ambident reactivity of the nitrite ion has been found to be the cause of the complex product formation observed, which can be controlled by a neighbouring equatorial ester group. Both N-attack and O-attack occur in the absence of the ester group, whereas O-attack is favoured in its presence. A neighbouring group assistance mechanism is proposed, in addition to steric effects, based on secondary interactions between the neighbouring ester group and the incoming nucleophile. High-level quantum mechanical calculations were carried out in order to delineate this effect. The theoretical results are in excellent agreement with experiments, and suggest a catalytic role for the neighbouring equatorial ester group.
[Show abstract][Hide abstract] ABSTRACT: Glyconanomaterials have shown high potential in applications including bioanalysis and nanomedicine. Here, a quantitative analytical technique, based on isothermal titration calorimetry, was developed to characterize the interactions between glyconanoparticles and lectins. By titrating lectins into the glyconanoparticle solution, the apparent dissociation constant, thermodynamic parameters, and the number of binding sites were derived simultaneously. For the glyconanoparticles-lectin binding pairs investigated, a 3-5 order of magnitude affinity enhancement over the free ligand-lectin interactions was observed which can be attributed to the multivalent ligand presentation on the nanoparticles. The impact of ligand density was also studied, and results showed that the affinity increased with the number of glycans on the nanoparticle.
[Show abstract][Hide abstract] ABSTRACT: Organosilicon-mediated, regioselective acetylation of vicinal- and 1,3-diols is presented. Methyl trimethoxysilane or dimethyl dimethoxysilane was first used to form cyclic 1,3,2-dioxasilolane or 1,3,2-dioxasilinane intermediates, and subsequent acetate-catalyzed monoacylation was efficiently performed by addition of acetic anhydride or acetyl chloride under mild conditions. The reaction exhibited high regioselectivity, resulting in the same protection pattern as in organotin-mediated schemes.
Chemical Communications 04/2012; 48(43):5370-2. · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dynamic hemithioacetal systems were efficiently generated in organic solvents and subsequently allowed to react with a range of lipases. This resulted in direct, dynamic asymmetric transformation of the systems, leading to optically active 1,3-oxathiolan-5-one products. The tandem process identified lipase-catalyzed lactonization as a useful method for the resolution of optimal constituents with high chemo- and stereoselectivities.
[Show abstract][Hide abstract] ABSTRACT: Organotin-mediated regioselective protection has been extensively used in organic synthesis for many years. However, the mechanistic origin of the resulting regioselectivity is still not clear. By the comparison of the steric and stereoelectronic effects controlling the geometry of five-membered rings formed from neighboring group participation, from intramolecular acyl group migration, or from orthoester transesterification on pyranoside rings, a theory on the pattern resulting from the reaction with dibutyltin oxide is presented. It is thus suggested that the regioselectivity of organotin-mediated protection is controlled by analogous steric and stereoelectronic effects as in neighboring group participation and acyl group migration, mainly dependent on the stereoelectronic effects of the pyranoside itself, and not related to complex stannylene structures. An organotin protection mechanism is also suggested, emanating from steric and stereoelectronic effects, nucleophilicity, and organotin acyl migration.
The Journal of Organic Chemistry 02/2012; 77(3):1457-67. · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The photoinitiated radical reactions between thiols and alkenes/alkynes (thiol-ene and thiol-yne chemistry) have been applied to a functionalization methodology to produce carbohydrate-presenting surfaces for analyses of biomolecular interactions. Polymer-coated quartz surfaces were functionalized with alkenes or alkynes in a straightforward photochemical procedure utilizing perfluorophenylazide (PFPA) chemistry. The alkene/alkyne surfaces were subsequently allowed to react with carbohydrate thiols in water under UV-irradiation. The reaction can be carried out in a drop of water directly on the surface without photoinitiator, and any disulfide side products were easily washed away after the functionalization process. The resulting carbohydrate-presenting surfaces were evaluated in real-time studies of protein-carbohydrate interactions using a quartz crystal microbalance (QCM) flow-through system with recurring injections of selected lectins, with intermediate regeneration steps using low pH buffer. The resulting methodology proved fast, efficient and scalable to high-throughput analysis formats, and the produced surfaces showed significant protein binding with expected selectivities of the lectins used in the study.