A concise and practical synthesis of oseltamivir phosphate(Tamiflu) from d-mannose

A short and practical synthesis of oseltamivir phosphate was accomplished in 11 steps from inexpensive and abundant starting material, d-mannose. This synthetic route featured an intramolecular Horner–Wadsworth–Emmons reaction as the key step to furnish the cyclohexene ring product. The hydroxyl group was converted stereo specifically into an amino group by oxidation to the ketone and reductive amination whereas the second amino group was introduced by azide substitution of a hydroxyl group. This synthesis provided an economical and practical alternative for the synthesis of Tamiflu.     

Thermoset polyester as an alternative material for microchip electrophoresis/electrochemistry

Microchip CE coupled with electrochemical detection (MCE-EC) is a good method for the direct detection of many small molecule analytes because the technique is sensitive and readily miniaturized. Polymer materials are being increasingly used with MCE due to their affordability and ease of fabrication. While PDMS has become arguably the most widely used material in MCE-EC due to the simplicity of microelectrode incorporation, it suffers from a lack of separation efficiency, lower surface stability, and a tendency for analyte sorption. Other polymers, such as poly(methylmethacrylate) (PMMA) and poly(carbonate) (PC), have higher separation efficiencies but require more difficult fabrication techniques for electrode incorporation. In this report, thermoset polyester (TPE) was characterized as an alternative material for MCE-EC. TPE microchips were characterized in their native and plasma oxidized forms and after coating with polyelectrolyte multilayers (PEMs). TPE provides higher separation efficiencies when compared to PDMS microchips, while still using simple fabrication protocols. In this work, separation efficiencies as high as 295,000 N/m were seen when using TPE MCE-EC devices. Furthermore, the EOF was higher and more consistent as a function of pH for both native and plasma-treated TPE than PDMS. Finally, TPE is amenable to modification using simple PEM coatings as another way to control surface chemistry and surface charge.     

Poly(dimethylsiloxane) cross-linked carbon paste electrodes for microfluidic electrochemical sensing

Recently, the development of electrochemical biosensors as part of microfluidic devices has garnered a great deal of attention because of the small instrument size and portability afforded by the integration of electrochemistry in microfluidic systems. Electrode fabrication, however, has proven to be a major obstacle in the field. Here, an alternative method to create integrated, low cost, robust, patternable carbon paste electrodes (CPEs) for microfluidic devices is presented. The new CPEs are composed of graphite powder and a binder consisting of a mixture of poly(dimethylsiloxane) (PDMS) and mineral oil. The electrodes are made by filling channels molded in previously cross-linked PDMS using a method analogous to screen printing. The optimal binder composition was investigated to obtain electrodes that were physically robust and performed well electrochemically. After studying the basic electrochemistry, the PDMS-oil CPEs were modified with multi-walled carbon nanotubes (MWCNT) and cobalt phthalocyanine (CoPC) for the detection of catecholamines and thiols, respectively, to demonstrate the ease of electrode chemical modification. Significant improvement of analyte signal detection was observed from both types of modified CPEs. A nearly 2-fold improvement in the electrochemical signal for 100 μM dithiothreitol (DTT) was observed when using a CoPC modified electrode (4.0 ± 0.2 nA (n = 3) versus 2.5 ± 0.2 nA (n = 3)). The improvement in signal was even more pronounced when looking at catecholamines, namely dopamine, using MWCNT modified CPEs. In this case, an order of magnitude improvement in limit of detection was observed for dopamine when using the MWCNT modified CPEs (50 nM versus 500 nM). CoPC modified CPEs were successfully used to detect thiols in red blood cell lysate while MWCNT modified CPEs were used to monitor temporal changes in catecholamine release from PC12 cells following stimulation with potassium.     

A polymer surface for antibody detection by using surface plasmon resonance via immobilized antigen

A polymer substrate based surface plasmon resonance (SPR) technique was developed for detection of specific monoclonal antibody 10B2 (MAb 10B2) against bacterium Acidovorax avenae subsp. citrulli (Aac). The monolayer of Aac antigen was physically immobilized on 95:5 polystryrene – copoly acrylic acid (95PSMA) for detection of antibody. The amount of antigen–antibody binding was found to depend on the surface density of immobilized Aac on the sensor surface and the antibody concentration. The detection limit was 5 μg/ml which was lower than the required concentration during the normal production of the antibody at 10–100 μg/ml. This suggests a possible use of surface for the antibody screening. Moreover, an application in antibody screening was explored by combination of surface plasmon resonance imaging (SPR imaging) and antibody detection assay on the 95PSMA surface. Two antigens of bovine serum albumin (BSA) and Aac were used as a model system for antibody screening. The result shows that both antibodies can be distinguished using the immobilized antigens on the 95PSMA surface based SPR imaging technique.     

Synthesis of Betamethasone From the Waste of Thai Agave Sisalana

Synthesis of betamethasone from waste of Thai A. sisalana is described.     

A new approach to asymmetric synthesis of (−)-epiquinamide from d-glucose

The asymmetric total synthesis of (?)-epiquinamide has been achieved starting from a 5-iodofuranoside synthon derived from d-glucose. The methods featured Bernet-Vasella reaction followed by Horner-Wadsworth-Emmons (HWE) reaction to provide a new chiral building block diene as the key steps. The bicyclic framework of this quinolizidine was constructed by selective reduction of α,β-unsaturated ester, intramolecular nucleophilic substitution and ring-closing metathesis.     

Adsorption of bovine serum albumin (BSA) on polystyrene (PS) and its acid copolymer

The effect of surface polarity on the adsorption of bovine serum albumin (BSA) on polystyrene (PS), 7% polystyrene-co-maleic anhydride (7%PSMAn) and 50% polystyrene-co-maleic acid (50%PSMA), at pH 7.4, was investigated. Polystyrene represented the non-polar surface while 7%PSMAn and 50%PSMA represented a low and high acid content copolymer. The amount of the adsorbed BSA depended on the amount of the acid content in the copolymer. BSA formed a monolayer with a side-on orientation on the low polarity PS surface, a mixed side-on and end-on orientation on 7%PSMAn and a predominantly side-on orientation on 50%PSMA. The thickness of adsorbed BSA, measured with an atomic force microscope (AFM), varied from 3 nm to 5 nm for the side-on orientation and from 10 nm to 15 nm for the end-on orientation. The average area occupied per BSA molecule was consistent with the proposed orientation, and was 34.8 nm², 27.8 nm² and 18.0 nm² for PS, 7%PSMAn and 50%PSMA, respectively. The adsorption showed a concentration dependency following the Freundlich isotherm, which indicated the interactions among adsorbed BSA molecules on the polymer surface. The adsorption took place as an island-like morphology and started to fuse into a patch-like morphology at higher concentrations before achieving a complete monolayer formation. A non-uniform surface coverage and defects were observed in all cases. It is recommended that for an effective blocking of PS, 7%PSMAn and 50%PSMA, the BSA concentration should be higher than 3 mg/mL.