Synthesis of N-glycosyl amides: conformational analysis and evaluation as inhibitors of ß-galactosidase from E. coli.

The synthesis of N-glycosyl amides typically involves the use of glycosyl amines as direct precursors, resulting in low yields due to hydrolysis and the loss of stereocontrol through anomerization processes. In this study, a sequential synthesis of N-glycosyl amides is proposed, employing glycosyl amines as intermediates obtained from glycosyl azides. Derivatives with gluco, galacto, or xylo configurations were synthesized. Hexose derivatives were obtained under stereocontrol to give only the ß anomer, while the xylo derivatives provided a mixture of α and ß anomers. Conformational analysis revealed that all ß anomers adopted the 4C1 conformation, while α anomers were found in the 1C4 chair as the major conformer. After de-O-acetylation, the derivatives containing a galactose unit were evaluated as inhibitors of ß-galactosidase from E. coli and were found to be moderate inhibitors.

Vapor Nanobubbles around Heated Nanoparticles: Wetting Dependence of the Local Fluid Thermodynamics and Kinetics of Nucleation.

Plasmonic nanobubbles are composite objects resulting from the interaction between light and metallic nanoparticles immersed in a fluid. Plasmonic nanobubbles have applications in photothermal therapies, drug delivery, microfluidic manipulations, and solar energy conversion. Their early formation is, however, barely characterized due to the short time and length scales relevant to the process. Here, we investigate, using molecular dynamics (MD) simulations, the effect of nanoparticle wettability on both the local fluid thermodynamics and the kinetics of nanobubble generation in water. We first show that the local onset temperature of vapor nucleation decreases with the nanoparticle/water interfacial energy and may be 100 K below the water spinodal temperature in the case of weak nanoparticle/water interactions. Second, we demonstrate that vapor nucleation may be slower in the case of weak water/nanoparticle interactions. This result, which is qualitatively at odds with the predictions of isothermal classical nucleation theory, may be explained by the competition between two antagonist effects: while, classically, hydrophobicity increases the vapor nucleation rate, it also penalizes interfacial thermal transfer, slowing down kinetics. The kinetics of heat transfer from the nanoparticle to water is controlled by the interfacial thermal conductance. This quantity turns out not only to decrease with the nanoparticle hydrophobicity but also drops down prior to phase change, yielding even longer nucleation times. Such conclusions were reached by considering the comparison between MD and continuous heat transfer models. These results put forward the role of nanoparticle wettability in the generation of plasmonic nanobubbles observed experimentally and open the path to the control of boiling using nanopatterned surfaces.

Synthesis of sugar enones and their use as powerful synthetic precursors of thiodisaccharides.

Monosaccharide derivatives having a double bond conjugated to a carbonyl (sugar enones or enuloses) are relevant synthetic tools. They are also suitable starting materials, or versatile intermediates, for the synthesis of a wide variety of natural or synthetic compounds with a broad spectrum of biological and pharmacological activities. The preparation of enones is mainly focused on the search for more efficient and diastereoselective synthetic methodologies. The usefulness of enuloses relies on the diverse reaction possibilities offered by alkene and carbonyl double bonds, which are prone to undergo varied reactions such as halogenation, nitration, epoxidation, reduction, addition, etc. The addition of thiol groups that led to sulfur glycomimetics, such as thiooligosaccharides, is particularly relevant. Therefore, the synthesis of enuloses and the Michael addition of sulfur nucleophiles to give thiosugars or thiodisaccharides are discussed here. Chemical modifications of the conjugate addition products to afford biologically active compounds are also reported.

Synthesis of thiodisaccharides related to 4-thiolactose. Specific structural modifications increase the inhibitory activity against E. coli ß-galactosidase.

In the search for new glycosidase inhibitors, a set of benzyl ß-D-Gal-S-(1→4)-3-deoxy-4-thio-α-D-hexopyranosides was synthesized. Diverse configurations were installed at C-2 and C-4 of the glucose residue. The benzyl glycosidic group was kept intact or substituted by an electron-donating or electron-withdrawing group that could also participate in hydrogen bonding. All thiodisaccharides were found to be inhibitors of E. coli ß-galactosidase. In general, benzyl thiodisaccharides were better inhibitors than those substituted (NO2 or NH2) on the benzyl ring. Thiodisaccharides containing a hexopyranoside, instead of a pentopyranoside, showed a weaker inhibitory activity, except for those having the α-D-xylo configuration, which exhibited inhibition constants of the same order of magnitude. These and previous results indicated that the inhibition process by thiodisaccharides is strongly dependent on the configuration of the 3-deoxy-4-thiopyranoside, as well as its substitution pattern (such as the presence of a benzyl glycoside). The enzyme-inhibitor interaction during the hydrolysis process involves a conformational selection resulting from rotation around the thioglycosidic bond and the flexibility of the terminal six-membered ring. Thus, the mentioned structural features of the inhibitor could give rise to favorable ground state conformations for the interaction with the enzyme, similar to those found for selected thiodisaccharides in the bound state. These studies demonstrated that the performance of thiodisaccharides as enzyme inhibitors could be increased by selecting the appropriate configuration and substitution of the hexopyranoside replacing the glucose moiety of 4-thiolactose.

Carbohydrate-Derived Polytriazole Nanoparticles Enhance the Anti-Inflammatory Activity of Cilostazol.

Poly(amide-triazole) and poly(ester-triazole) synthesized from d-galactose as a renewable resource were applied for the synthesis of nanoparticles (NPs) by the emulsification/solvent evaporation method. The NPs were characterized as stable, spherical particles, and none of their components, including the stabilizer poly(vinyl alcohol), were cytotoxic for normal rat kidney cells. These NPs proved to be useful for the efficient encapsulation of cilostazol (CLZ), an antiplatelet and vasodilator drug currently used for the treatment of intermittent claudication, which is associated with undesired side-effects. In this context, the nanoencapsulation of CLZ was expected to improve its therapeutic administration. The carbohydrate-derived polymeric NPs were designed taking into account that the triazole rings of the polymer backbone could have attractive interactions with the tetrazole ring of CLZ. The activity of the nanoencapsulated CLZ was measured using a matrix metalloproteinase model in a lipopolysaccharide-induced inflammation system. Interestingly, the encapsulated drug exhibited enhanced anti-inflammatory activity in comparison with the free drug. The results are very promising since the stable, noncytotoxic NP systems efficiently reduced the inflammation response at low CLZ doses. In summary, the NPs were obtained through an innovative methodology that combines a carbohydrate-derived synthetic polymer, designed to interact with the drug, ease of preparation, adequate biological performance, and environmentally friendly production.

Size-dependent effects of the thermal transport at gold nanoparticle-water interfaces.

The transfer of heat from a plasmonic nanoparticle to its water environment has numerous applications in the fields of solar energy conversion and photothermal therapies. Here, we use nonequilibrium molecular dynamics to investigate the size dependence of the interfacial thermal conductance of gold nanoparticles immersed in water and with tunable wettability. The interfacial thermal conductance is found to increase when the nanoparticle size decreases. We rationalize such a behavior with a generalized acoustic model, where the interfacial bonding decreases with the nanoparticle size. The analysis of the interfacial thermal spectrum reveals the importance of the low frequency peak of the nanoparticle spectrum as it matches relatively well the oxygen peak in the vibrational spectrum. However, by reducing the nanoparticle size, the low frequency peak is exacerbated, explaining the enhanced heat transfer observed for small nanoparticles. Finally, we assess the accuracy of the continuum heat transfer equations to describe the thermal relaxation of small nanoparticles with initial high temperatures. We show that, before the nanoparticle loses its integrity, the continuum model succeeds in describing with small percentage deviations the molecular dynamics data. This work brings a simple methodology to understand, beyond the plasmonic nanoparticles, thermal boundary conductance between a nanoparticle and its environment.

Turmell-Meter: A Device for Estimating the Subtalar and Talocrural Axes of the Human Ankle Joint by Applying the Product of Exponentials Formula.

The human ankle is a complex joint, most commonly represented as the talocrural and subtalar axes. It is troublesome to take in vivo measurements of the ankle joint. There are no instruments for patients lying on flat surfaces; employed in outdoor or remote sites. We have developed a "Turmell-meter" to address these issues. It started with the study of ankle anatomy and anthropometry. We also use the product of exponentials' formula to visualize the movements. We built a prototype using human proportions and statistics. For pose estimation, we used a trilateration method by applying tetrahedral geometry. We computed the axis direction by fitting circles in 3D, plotting the manifold and chart as an ankle joint model. We presented the results of simulations, a prototype comprising 45 parts, specifically designed draw-wire sensors, and electronics. Finally, we tested the device by capturing positions and fitting them into the bi-axial ankle model as a Riemannian manifold. The Turmell-meter is a hardware platform for human ankle joint axes estimation. The measurement accuracy and precision depend on the sensor quality; we address this issue by designing an electronics capture circuit, measuring the real measurement with a Vernier caliper. Then, we adjust the analog voltages and filter the 10-bit digital value. The Technology Readiness Level is 2. The proposed ankle joint model has the properties of a chart in a geometric manifold, and we provided the details.

Photooxidation of thiosaccharides mediated by sensitizers in aerobic and environmentally friendly conditions.

A series of ß-d-glucopyranosyl derivates have been synthesized and evaluated in photooxidation reactions promoted by visible light and mediated by organic dyes under aerobic conditions. Among the different photocatalysts employed, tetra-O-acetyl riboflavin afforded chemoselectively the respective sulfoxides, without over-oxidation to sulfones, in good to excellent yields and short reaction times. This new methodology for the preparation of synthetically useful glycosyl sulfoxides constitutes a catalytic, efficient, economical, and environmentally friendly oxidation process not reported so far for carbohydrates.

Intramolecular azide-alkene cycloaddition-elimination reaction in an aldohex-2-enonic acid derivative.

A 6-azido-2-tosylenolate, obtained from D-glucono-1,5-lactone in six steps, underwent an intramolecular cycloaddition-elimination pathway under mild conditions, yielding a chiral, substituted 5,6-dihydro-4H-pyrrolo[1,2-c]-1,2,3-triazole. The conditions were optimized to give exclusive formation of the triazole. The mechanism appears to involve intramolecular ring closure via a 1,3-dipolar azide-alkene cycloaddition to give a 1,2,3-triazoline, followed by elimination of p-toluenesulfonic acid, leading to aromatization. Triazole products, obtained by chemical modification, are expected to display activity as enzyme inhibitors. Furthermore, partially protected derivatives of the 2-hexenoate were prepared as useful synthetic intermediates.

Implante inmediato postextracción en zona de alto compromiso estético utilizando la técnica del "Socket Shield", provisional inmediato y prótesis definitiva con un pilar transepitelial customizado de circonio / Immediate post-extraction implant in a high aesthetic area using "Socket Shield" technique, immediate provisional, and definitive prosthesis with a customized zirconia transepithelial abutment

El objetivo de este trabajo es demostrar la estabilidad de los tejidos que rodean a un implante inmediato tras la realización de una extracción parcial de un diente. La técnica de Socket Shield fue descrita por primera vez por Hürzeler y cols., con la finalidad de preservar el volumen y la posición de los tejidos, así como el nivel original de la cortical vestibular tras la exodoncia, manteniendo un fragmento de la raíz dental a la par que se inserta un implante dental en el mismo alveolo y respetando una distancia entre ambos de uno o dos milímetros y que deberá ser ocupado por el coágulo sanguíneo. A continuación, se expone un caso clínico de una mujer de 42 años de edad que acudió de urgencia por una fractura dental en zona estética. El plan de tratamiento implica la extracción del incisivo central superior derecho y su posterior rehabilitación fija. Se colocó un implante Biohorizons(R) a 40N, 72 ISQ, postextracción y empleando la técnica de Socket-shield con una restauración inmediata temporal no funcional. Transcurridas 16 semanas, se conectó un pilar transepitelial personalizado de circonio y se cementó la corona Emax2. Transcurridos 12 meses de carga funcional, no ha habido complicaciones quirúrgicas ni protésicas. El volumen y la forma original de la cortical vestibular no se han visto clínicamente alteradas, el fragmento radicular se encuentra estable y los tejidos blandos circundantes están en armonía con el pilar transepitelial de circonio, cuya altura de 4 mm aleja la interfase pilar-corona de la interfase pilar-implante en pro de la estabilidad tisular en ese plano. Se ha conseguido estabilizar los tejidos periimplantarios con la técnica Socket Shield y salvaguardar el compromiso estético que implica la pérdida de un incisivo central superior

The objective of this work is to demonstrate the stability of the tissues surrounding an inmediate implant after performing a partial extraction. The Socket Shield technique was described by Hürzeler et all in 2010 with the main goal of preserve the volume and the initial position of the soft-tissues and the buccal plate after the tooth extraction, keeping a piece of the buccal dental root into the alveolar socket at same time of the dental implantation, maintaining a security distance of 1 or 2 millimetres, that should be occupied by the blood cloth. In this Clinical case, a female of 42 years old, with a broken teeth's crown requires dental implant treatment. The planning needs teeth extraction at the upper maxilla and posterior rehabilitation with fixed implant prosthesis. It was inserted a Biohorizons(R) dental implant, using the Socket Shield technique after the partial extraction of the teeth. An immediate provisional prosthesis was connected. 16 weeks later; it was substituted by a customized zirconia abutment to make prosthesis over it. After 12 months of functional load, nonsurgical or prosthesis complications were described. The volume and the original shape of the buccal bone plate do not showed clinical changes, the root piece is stable and the zirconia customized abutment maintains an implant rehabilitation connection far away of the biological width. The Socket Shield technique stabilizes the periimplant tissues and preserves the biological width of the immediate dental implant using a customized zirconia abutment

Synthesis of enantiomerically pure enones (2-benzyloxypyran-3-ones) derived from pentoses.

The useful synthons sugar enones (2-benzyloxypyran-3-ones) derived from pentoses have been prepared starting from 2-acetoxyglycals or benzyl pentopyranosides. The glycals were glycosylated with benzyl alcohol in the presence of a Lewis acid (SnCl4 or InCl3) to give enantioenriched enones (ee = 80-90%). Under catalysis with InCl3, benzyl 2-enopyranosides gave also the enones (ee = 87%). On the other hand, enantiomerically pure enones were synthesized via an improved straightforward and high yielding sequence (70% overall) from benzyl pentopyranosides. However, the yields of both, the glycosylation of glycals as well as some specific reactions of the sequence from glycosides, were lowered when a p-nitro substituent was introduced into the benzyl group. These routes became impractical in the case of p-acetamidobenzyl derivatives, because of the large extent of decomposition. Therefore, alternative sequences have been developed for the synthesis of 2-(p-acetamidobenzyloxy)pyran-3-ones.

Synthesis, characterization and chemical degradation of poly(ester-triazole)s derived from d-galactose.

α-Azide-ω-alkynyl ester monomers were designed and synthesized in order to obtain hydrolytically degradable polymers. The monomers were prepared from d-galactose, as a renewable resource. Environmentally benign azido-alkyne cycloaddition polymerizations were conducted to afford poly(ester-triazole)s, with complete atom economy. Although polymer formation prevailed under optimized polymerization conditions, variable proportions of cyclic oligomer byproducts were detected. The Cu-catalyzed click polymerization led regioselectively to 1,4-disubstituted triazole linkages, while the thermal, metal-free polymerization produced a random distribution of 1,4- and 1,5-disubstituted triazoles in the polymer backbone. The poly(ester-triazole)s exhibited high molecular weights (M w in the range 35-85 kDa). They were soluble in organic solvents but highly insoluble in water, thus removal of the Cu(i) catalyst was simplified. The polymers were stable up to 300 °C, and had T g values in the range 90-100 °C. The materials were hydrolysed under either basic or strong acid conditions, and the degradation products have been characterized.

Renal graft survival in patients transplanted from organs of deceased donors / Sobrevida del injerto renal en pacientes trasplantados de órganos de donadores fallecidos

Background: In Mexico, out of the total number of transplants it was reported, in 2014, a frequency of 29% of deceased donor renal transplantation (DDRT). The use of kidneys from deceased elderly donors is increasing over the years. Currently, some authors consider that six months after the transplant, patients who have been transplanted from deceased donors have a longer survival than those who are still undergoing dialysis replacement therapy. Objective: To observe and describe the results of renal graft function and survival of patients with DDRT during the first six months after transplantation, and show the frequencies of complications, as well as graft and death nephrectomy. Material and methods: A series of cases with taxonomy of retrospective, retrolective, descriptive with frequencies and correlational with association of variables, from January 2014 to July 2015; statistical analysis was performed using SPSS, version 17. Results: Renal graft's survival was 79.5%. Serum creatinine levels were 0.6 to 2.5 mg/dL with an average of 1.2. CKD-EPI index was estimated from 29 to 120 mL/min/1.73 m2 with an average of 71.4. We found 57% with glomerular filtration rate above 60 (the CKD-EPI level). Conclusion: DDRT continues to be a favorable option for patients with chronic renal failure, even with the extended criteria of the deceased donor.

Introducción: en nuestro país, del total de trasplantes se reportó, en el 2014, una frecuencia del 29% de trasplante renal de donador fallecido (TRDF). El uso de riñones procedentes de donante fallecido de edad avanzada está aumentando al paso de los años. Actualmente, algunos autores consideran que a los seis meses después del trasplante los pacientes que han sido trasplantados de donador fallecido tienen una mayor supervivencia que los que siguen aún en tratamiento sustitutivo con diálisis. Objetivo: observar y describir los resultados de la función y sobrevida del injerto renal de los pacientes con TRDF durante los primeros seis meses del postrasplante, y mostrar las frecuencias de complicaciones, así como también nefrectomía de injerto y defunción. Métodos: serie de casos con taxonomía de tipo retrospectivo, retrolectivo, descriptivo con frecuencias y correlacional con asociación de variables, realizada de enero del 2014 a julio del 2015; el análisis estadístico de las variables se hizo mediante el paquete SPSS, versión 17. Resultados: la sobrevida del injerto renal fue del 79.5%. Los niveles de creatinina sérica fueron de 0.6 a 2.5 mg/dL con una media de 1.2. El índice CKD-EPI se estimó de 29 a 120 mL/min/1.73 m2, con una media de 71.4. Encontramos un 57% con filtrado glomerular por arriba del 60 de CKD-EPI. Conclusión: el trasplante renal de donador fallecido continúa siendo una opción favorable para los pacientes con insuficiencia renal crónica, aun con los criterios extendidos del donador fallecido.

Estabilización clínica de los tejidos periimplantarios mediante la combinación de la técnica "Socket Shield" y el pilar múltiple PGMU2 / Clinical stabilization of the periimplant tissues with the combination of the socket shield technique and the PGMU2 abutment

La técnica de Socket Shield fue descrita por primera vez por Zuhr y cols., en el año 2010 con la finalidad de preservar el volumen y la posición de los tejidos, así como el nivel original de la cortical vestibular tras la exodoncia, manteniendo un fragmento de la raíz dental a la par que se inserta un implante dental en el mismo alveolo y respetando una distancia entre ambos de uno o dos milímetros y que deberá ser ocupado por el coágulo sanguíneo. Caso clínico de un varón de 79 años de edad, con edentulismo parcial que es diagnosticado para tratamiento implantológico. El plan de tratamiento implica la extracción de dientes remanentes en maxilar superior y su posterior rehabilitación fija. Se colocaron dos implantes Biohorizons(R), uno de ellos postextracción, empleando la técnica de Socket-shield. Transcurridas 12 semanas, se conectó un pilar de cicatrización, 5 semanas después, se sustituyó el tapón por un pilar múltiple tipo Multi-unit(R) para confeccionar la prótesis fija. Transcurridos 12 meses de carga funcional, no habido complicaciones quirúrgicas ni protésicas. El volumen y la forma original de la cortical vestibular no se ha visto clínicamente alterada, el fragmento radicular se encuentra estable y el pilar PGMU2 ha permitido la rehabilitación del implante alejando la conexión de la prótesis del espacio biológico. Se ha conseguido estabilizar los tejidos periimplantarios con la técnica Socket Shield y salvaguardar el espacio biológico del implante inmediato con el pilar múltiple

The Socket Shield technique was described by Zuhr et all in 2010 with the main goal of preserve the volume and the initial position of the soft-tissues and the buccal plate after the tooth extraction, keeping a piece of the buccal dental root into the alveolar socket at same time of the dental implantation, keeping a security distance of 1 or 2 millimetres, that it should be occupied by the blood cloth. In this Clinical case, a male of 79 years old with partial edentulism requires dental implant treatment. The planning needs tooth extractions at the upper maxilla and posterior rehabilitation with fixed implant prosthesis. It was inserted two Biohorizons(R)dental implants, one of theme was after tooth extraction and using the Socket Shield technique. After 12 weeks, it was connected a healing abutment, 5 weeks later, It was substituted by a Multi-unit(R) abutment to make a prosthesis over it. After 12 months of functional load, non-surgical or prosthesis complications were described. The volume and the original shape of the buccal bone plate do not showed clinical changes, the root piece is stable and the PGMU2 abutment maintains an implant rehabilitation connection far away of the biological width. The Socket Shield technique stabilizes the periimplant tissues and preserves the biological width of the immediate dental implant using a Muti-unit(R) abutment

Design and Synthesis of 2-Acetamido-2,3-dideoxythiodisaccharides via Diastereoselective Conjugate Addition to Sugar Enone O-Acetyl Oximes. Galactosidase Inhibition Studies.

The key step in a new synthesis of 2-acetamido-2,3-dideoxy-(1→4)-thiodisaccharides was the conjugate addition of a 1-thiogalactose derivative to E and Z acetyl oximes derived from sugar enones. This reaction was shown to be completely diastereoselective for both the formation of the thioglycosidic linkage and the configuration of acetyl oxime. The thiodisaccharides have been designed as inhibitors of the ß-galactosidase from E. coli, and they have been shown to successfully meet such requirements.

Synthesis of ß-galactosylamides as ligands of the peanut lectin. Insights into the recognition process.

The synthesis of mono and divalent ß-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived from l-tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from ß-galactosylamine and succinic anhydride. After functionalization with an alkynyl residue, the resulting building blocks were grafted onto different azide-equipped scaffolds through the copper catalyzed azide-alkyne cycloaddition. Thus, a family of structurally related mono and divalent ß-N-galactopyranosylamides was obtained and fully characterized. The binding affinities of the ligands towards the model lectin PNA were measured by the enzyme-linked lectin assay (ELLA). The IC50 values were significantly higher than that of galactose but the presence of hydroxyl groups in the aglycone chain improved lectin recognition. Docking and molecular dynamics experiments were in accordance with the hypothesis that a hydroxyl group properly disposed in the linker could mimic the Glc O3 in the recognition process. On the other hand, divalent presentation of the ligands led to lectin affinity enhancements.

Synthesis of Enantiomeric Polyhydroxyalkylpyrrolidines from 1,3-Dipolar Cycloadducts. Evaluation as Inhibitors of a ß-Galactofuranosidase.

Enantiomeric 2,3,4-tris(hydroxyalkyl)-5-phenylpyrrolidines have been synthesized from the major cycloadducts obtained by the 1,3-dipolar cycloaddition of sugar enones with azomethine ylides derived from natural amino acids. Reduction of the ketone carbonyl group of the cycloadducts, which possess a basic structure of bicyclic 6-(menthyloxy)hexahydropyrano[4,3-c]pyrrol-7(6H)one, afforded a number of pyrrolidine-based bicyclic systems. A sequence of reactions, which involved hydrolysis of the menthyloxy substituent, reduction, N-protection, and degradative oxidation, afforded varied pyrrolidine structures having diverse configurations and patterns of substitution; in particular, polyhydroxylated derivatives have been obtained. The unprotected products were isolated as pyrrolidinium trifluoroacetates. Because of the furanose-like nature of the target trihydroxyalkyl pyrrolidines, these molecules have been evaluated as inhibitors of the ß-galactofuranosidase from Penicillium fellutanum. The compounds showed practically no inhibitory activity for concentration of pyrrolidines in the range of 0.1-1.6 mM.

String Theory Origin of Dyonic N=8 Supergravity and Its Chern-Simons Duals.

We clarify the higher-dimensional origin of a class of dyonic gaugings of D=4 N=8 supergravity recently discovered, when the gauge group is chosen to be ISO(7). This dyonically gauged maximal supergravity arises from consistent truncation of massive IIA supergravity on S^6, and its magnetic coupling constant descends directly from the Romans mass. The critical points of the supergravity uplift to new four-dimensional anti-de Sitter space (AdS4) massive type IIA vacua. We identify the corresponding three-dimensional conformal field theory (CFT3) duals as super-Chern-Simons-matter theories with simple gauge group SU(N) and level k given by the Romans mass. In particular, we find a critical point that uplifts to the first explicit N=2 AdS4 massive IIA background. We compute its free energy and that of the candidate dual Chern-Simons theory by localization to a solvable matrix model, and find perfect agreement. This provides the first AdS4/CFT3 precision match in massive type IIA string theory.

Stereospecific synthesis of pyrrolidines with varied configurations via 1,3-dipolar cycloadditions to sugar-derived enones.

Enantiomerically pure pyrrolidines have been obtained by 1,3-dipolar cycloaddition of stabilized azomethine ylides and sugar enones (dihydropyranones) derived from pentoses. Thus, the S-enone (menthyl 3,4-dideoxy-(1S)-pent-3-enopyranosid-2-ulose) was prepared from D-xylose, while the R analogue was obtained from L-arabinose. The dipoles were generated in situ from α-arylimino esters of common amino acids (glycine, alanine, or phenylalanine) and aromatic aldehydes (benzaldehyde, 3-formylpyridine and 4-methoxybenzaldehyde). Under optimized conditions, the cycloaddition reactions were highly diastereo- and regioselective to yield, in most of the cases, a very major adduct of the 16 theoretically possible. The diastereoselectivity relies on the strict stereocontrol exerted by the stereogenic center of the pyranone. Thus, the (S)-enone, derived from D-xylose, gave tetrasubstituted pyrrolidines having a defined stereochemistry for the four stereocenters of the ring, while they had the opposite configuration when starting from the (R)-dihydropyranone. Furthermore, some endo-cycloadducts underwent isomerization of the carbons vicinal to the nitrogen atom to afford pyrrolidines with a rather unusual stereochemistry for the direct dipolar cycloadditions.

Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose.

We report here the synthesis of divalent ligands containing 3-deoxy-4-thiolactose. This thiodisaccharide has been synthesized using the Michael addition of ß-1-thiogalactose to the α,ß-unsaturated system of sugar-derived dihydropyranones, followed by the reduction of the remaining carbonyl group. We were able to control the configuration (S) of the stereocenter linked to sulfur (C-4) of the reducing end by conducting the thioglycosylation at high temperature or by isomerization during the reduction of the 2-ulose thiodisaccharide with NaBH4/THF. The energy profile for this reaction on a model compound was calculated. The anomeric position of the 3-deoxy-4-thiolactose was functionalized with a terminal alkyne, which was coupled to azide-containing sugar scaffolds through CuAAC reaction to afford mono- and divalent ligands. The final products were competitive inhibitors of E. coli ß-galactosidase in the micromolar range. Their binding affinities to peanut agglutinin (PNA) were determined by isothermal calorimetry, which showed a clear decrease in the Ka values for monovalent derivatives compared to lactose. This report contributes to establishing the role of a particular hydroxyl group of lactose in sugar-protein recognition processes.