Preparation of a boronate-functionalized affinity hybrid monolith for specific capture of glycoproteins

A novel strategy for preparation of a boronate affinity hybrid monolith was developed using a Cu(I)-catalyzed 1,3-dipolar azide–alkyne cycloaddition (CuAAC) reaction of an alkyne–boronate ligand with an azide-functionalized monolithic intermediate. An azide-functionalized hybrid monolith was first synthesized via a single-step procedure to provide reactive sites for click chemistry; then the alkyne–boronate ligands were covalently immobilized on the azide-functionalized hybrid monolith via an in-column CuAAC reaction to form a boronate affinity hybrid monolith under mild conditions. The boronate affinity monolith was characterized and evaluated by means of elemental analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The boronate affinity hybrid monolith exhibited excellent specificity toward nucleosides and glycoproteins, which were chosen as test cis-diol-containing compounds under neutral conditions. The binding capacity of the monolith for the glycoprotein ovalbumin was 2.36 mg?·?g^-1 at pH 7.0. The practicability of the boronate affinity hybrid monolithic material was demonstrated by specific capture of the glycoproteins ovalbumin and ovotransferrin from an egg sample.

基于巯基-烯点击反应制备有机-无机杂化硼酸亲和整体柱用于糖蛋白的选择性富集

发展了以巯基-烯点击反应制备有机-无机杂化硼酸亲和整体柱的新方法。首先以四甲氧基硅烷(TMOS)和巯丙基三甲氧基硅烷(MPTMS)作为反应单体,采用溶胶-凝胶反应制备表面含巯基的硅胶整体柱。然后利用巯基-烯(thiol-ene)的点击反应在整体柱上修饰硼酸配基3-丙烯酰胺基苯硼酸(AAPBA),制成AAPBA-硅胶杂化亲和整体柱。对影响硼酸亲和整体柱性能的条件如TMOS与MPTMS的比例、聚乙二醇和甲醇的用量等进行了优化。并采用扫描电镜、红外光谱等分析仪器对整体柱形貌和机械稳定性能进行了表征。研究了AAPBA-硅胶杂化亲和整体柱的分离性能,结果表明,其在中性条件下对含有顺式二醇的生物小分子核苷具有良好的特异亲和能力,并已成功地应用于卵清蛋白、辣根过氧化物酶等糖蛋白的分离。基于巯基-烯反应的制备方法新颖、可靠,可用于制备多种不同类型的硼酸亲和整体柱,具有较大的应用前景。     

One-pot synthesis of an organic-inorganic hybrid affinity monolithic column for specific capture of glycoproteins

An inorganic-organic hybrid affinity monolithic column was synthesized by a novel "one-pot" approach. The resulting hybrid affinity monoliths have potential applications in specific recognition and enrichment of glycoproteins.     

Preparation and evaluation of a phenylboronate affinity monolith for selective capture of glycoproteins by capillary liquid chromatography

A phenylboronate affinity monolith was prepared and applied to the selective capture of glycoproteins from unfractionated protein mixtures. The monolith was synthesized in a 100 μm i.d capillary by an in situ polymerization procedure using a pre-polymerization mixture consisting of 4-vinylphenylboronic acid (VPBA) as functional monomer, ethylene dimethacrylate (EDMA) as crosslinker, diethylene glycol and ethylene glycol as binary porogenic solvents, and azobisisobutyronitrile (AIBN) as initiator. The prepared monolith was characterized in terms of the morphology, pore property, and recognition property. The selectivity and dynamic binding capacity were evaluated by using standard glycoproteins and nonglycoproteins as model proteins. The chromatographic results demonstrated that the phenylboronate affinity monolith had higher selectivity and binding capacity for glycoprotein than nonglycoprotein. The resulting phenylboronate affinity monolith was used as the sorbent for in-tube solid phase microextraction (in-tube SPME), and the extraction performance of the monolith was assessed by capture of ovalbumin from egg white sample.     

Synthesis of hydrophilic boronate affinity monolithic capillary for specific capture of glycoproteins by capillary liquid chromatography

Boronate affinity chromatography is an important tool for specific isolation of cis-diol-containing compounds such as glycoproteins, RNA and carbohydrates. Boronate functionalized monolithic capillaries have been recently developed for specific capture of cis-diol-containing small biomolecules, but the apparent hydrophobicity of the columns prevents them from specific capture of glycoproteins. In this paper, a hydrophilic boronate affinity monolithic capillary was prepared by in situ free radical polymerization, using 4-vinylphenylboronic acid (VPBA) and N, N′-methylenebisacrylamide (MBAA) as functional monomer and cross-linker, respectively. The prepared poly(VPBA-co-MBAA) monolithic capillary exhibited uniform open channel network and high density of accessible boronic acid. Due to the utilization of hydrophilic cross-linker, the prepared column was hydrophilic, allowing for specific capture of glycoproteins.     

Synthesis and application of a macroporous boronate affinity monolithic column using a metal-organic gel as a porogenic template for the specific capture of glycoproteins

A macroporous boronate affinity monolithic column was prepared and applied to specifically capture glycoproteins using metal-organic gels (MOGs) as a porogenic template. This newly explored application of MOGs has proven to be a more convenient method for the formation of macropores in contrast to traditional porogenic methods. The poly (3-acrylamidophenylboronic acid-co-ethylene dimethacrylate) monolithic columns were synthesized in stainless columns by in situ polymerization. To fabricate the macroporous formation with a uniformed open-channel network, the preparation conditions, such as reaction temperature, the concentration of the MOGs and the ratio of monomers were systematically investigated. The prepared macroporous monoliths were characterized by scanning electron microscope (SEM) and mercury intrusion porosimetry. Furthermore, horseradish peroxidase (HRP) and transferrin (TF) were chosen as test glycoproteins, and the chromatographic analysis demonstrated that the macroporous boronate affinity monoliths exhibited a higher selectivity and better dynamic binding capacity toward glycoproteins compared with non-glycoproteins. The resulted affinity monolithic column was successfully employed to specifically capture TF from a bovine serum sample.     

Synthesis of 3-aminoisoxazolmethylnaphthols via one-pot three-component reaction under solvent-free conditions

A one-pot three-component condensation reaction of 3-amino-5-methylisoxazole, aryl aldehyde and 2-naphthol to afford the corresponding 3-amino isoxazolmethylnaphthols in good to excellent yields. The remarkable features of this new procedure are high conversions, clean reaction condition, short reaction time, nonhazardous and environmentally friendly reaction condition, inexpensive and easily commercially availability of the catalyst and simple work-up procedures.     

Synthesis and characterization of a new boronate affinity monolithic capillary for specific capture of cis-diol-containing compounds

Boronate affinity chromatography (BAC) is an important tool for specific capture and separation of cis-diol-containing compounds such as glycoproteins, RNA and carbohydrates. Only a few reports on monolithic column-based BAC have appeared. In this paper, boronate functionalized monolithic capillary column was synthesized by in situ free radical polymerization for the first time. The prepared column was first characterized in terms of morphology, pore properties, capacity and retention mechanisms. The column exhibited uniform open channel network and high capture capacity. Systematical investigation on the retention mechanism revealed that multiple intermolecular interactions occur between the analytes and the boronate affinity monolith, including boronate affinity, reversed-phase, cation-exchange and hydrogen bonding interactions, depending on the conditions used. In addition, the presence of Lewis base such as fluoride ion in the mobile phase was found to be favorable to the complexation between cis-diol-containing compounds with the boronic acid ligand under less basic conditions. On the basis of these fundamental investigations, the prepared monolithic column was then applied to the capture of adenosine and flavin adenine dinucleotide. The investigations in this study provide sound understanding not only on how to manipulate the separation selectivity through selection of appropriate mobile phase composition on the currently prepared columns but also on how to design next-generation columns with desired properties and functions.     

Synthesis of spiroketals under neutral conditions via a type III ring-rearrangement metathesis strategy

A conceptually novel approach to spiro- and dispiroketals of various ring-sizes under neutral conditions has been designed which complements the classical thermodynamically driven tactic. Key steps involved the formation of α-alkoxyfurans, their [4+2] or [4+3] cycloaddition reactions and the ring-rearrangement metathesis of the resulting oxabicycles.     

Synthesis of highly functionalized pyrrolidines via a mild one-pot, three-component 1,3-dipolar cycloaddition process

[reaction: see text] A simple and efficient one-pot, three-component synthesis of highly functionalized pyrrolidines via cascade imine --> azomethine ylide --> 1,3-dipolar cycloadditions is reported. Admixing a variety of aldehydes, dimethyl 2-aminomalonate, and electron deficient alkenes in THF leads to the clean production of pyrrolidines in good to excellent yields. The mild reaction conditions enabled the generation of previously inaccessible azomethine ylides from enolizable aldehydes. Endo selectivity was exclusive with N-phenyl maleimide and maleic anhydride. Good chemo-, regio-, and stereoselectivities were observed with methyl acrylate, though catalysis by Ag(I) was necessary with this dipolarophile.     

Synthesis of amine-modified mesoporous materials for CO2 capture by a one-pot template-free method

A one-pot template-free route was developed for the synthesis of novel tetraethylenepentamine modified porous silica as CO₂ adsorbents, the obtained materials were characterized by N₂ adsorption/desorption, thermogravimetry, elemental analysis, Fourier transform infrared spectrometry,scanning electron microscopy and transmission electron microscopy. It was found that the amine species were inserted into the silica skeleton, which considerably enhanced their dispersion. Compared with similar materials derived from impregnation, the porous structure of the silica can be better reserved, leading to a promising CO₂ adsorption capacity of 3.98 mmol CO₂/g-adsorbent and a fast adsorption kinetic in simulated flue gas at 348 K. The resulted adsorbents could also be easily regenerated and showed a good durability in multiple adsorption–desorption cycles. All these features make this method a promising option for the preparation of CO₂ adsorbents.     

A one-pot process for the enantioselective synthesis of amines via reductive amination under transfer hydrogenation conditions

[reaction: see text]. Cyclic amines may be prepared via a sequence of deprotection followed by intramolecular reductive amination of t-Boc-protected amino ketones under asymmetric transfer hydrogenation conditions. In cases where the corresponding imine reaction proceeds with high enantioselectivity, this is reflected in the one-step process.     

Preparation and formation mechanism of a n-butylammonium/MnO2 layered hybrid via a one-pot synthesis under moderate conditions

The preparation of organic/inorganic layered hybrids has relied on multistep processing. Thus, shortening the synthetic procedure is important for possible future applications, but only a few studies report one-pot syntheses. In this work, we established a simple one-pot solution process to synthesize layered alkyl ammonium/MnO(2) hybrids, by stirring MnCl(2) and alkyl amine/H(2)O(2) aqueous solutions at 40 °C; the reaction concept is a chemical oxidation of Mn(II) ions in the presence of alkyl amine in aqueous solution. Furthermore, the formation mechanism of the layered n-butylammonium/MnO(2) hybrid was examined by following the structural and optical changes during the reaction, revealing that the one-pot reaction includes 3 steps; formation of β-MnOOH, topotactic oxidation of β-Mn(III)OOH to form the protonated layered manganese oxide H(x)Mn(III, IV)O(2)·yH(2)O, and ion-exchange of interlayer H(+) (or H(3)O(+)) with n-butylammonium to form layered n-butylammonium/MnO(2).     

Straightforward assembly of phenylimidazoquinoxalines via a one-pot two-step MCR process

An efficient multicomponent-based methodology providing a new entry into a medicinally important complex heterocyclic core is presented. The strategy is very general and able to endow target compounds with the highest possible number of diversity points. Notably, four new chemical bonds and two aromatic rings are formed in a one-pot fashion.     

A self-assembled molecular team of boronic acids at the gold surface for specific capture of cis-diol biomolecules at neutral pH

We report a single-step strategy called self-assembled molecular team to generate boronate affinity ligands that can specifically capture cis-diol biomolecules at neutral pH, which provides three significant advantages: a simple procedure, high affinity and high specificity.     

Synthesis of thiohydantoins under one-pot three-component solvent-free conditions

A direct and efficient one-pot three-component synthesis protocol was developed for the synthesis of thiohydantoins from readily and widely available substrates (isothiocyanates, ethyl chloroacetate, and amines) employing solvent-free conditions. Correspondence: Song Cao, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.     

Synthesis of 1,2-disubstituted-3-alkylidenylpyrrolidines via a one-pot three-component reaction

Olsson’s three-component reaction of cyclopropylketones, aldehydes, and primary amines was investigated for application to parallel synthesis. Using an excess of Et₂AlI at elevated temperatures, pyrrolidines 4, the initial products reported by Olsson and co-workers, could be completely converted to pyrrolium salts 5, by a reaction sequence involving a retro-aza-Michael addition followed by iminium salt formation. The pyrrolium salts 5 were then cleanly reduced in situ by NaBH(OAc)₃ to give 3-alkylidenylpyrrolidines 6. In summary, this one-pot three-component reaction provided an efficient synthetic route to 3-alkylidenylpyrrolidines.     

Synthesis of 2-phosphonopyrroles via a one-pot RCM/oxidation sequence

A four-step synthesis of 2-phosphonopyrroles is presented starting from suitable aldehydes. The key step in the synthesis involves a one-pot ring-closing metathesis/oxidation sequence of a functionalized alpha-aminoalkenyl phosphonate. Notwithstanding the presence of a nucleophilic nitrogen atom and high substitution patterns in the substrate, the results of the RCM reaction are excellent using mild reaction conditions. Furthermore, a synergism is observed between the RCM catalyst and the oxidizing agent, causing higher oxidation rates and allowing reaction for substrates that normally fail to ring close under standard RCM conditions.     

Synthesis of 3-substituted 4-piperidinones via a one-pot tandem oxidation-cyclization-oxidation process: stereodivergent reduction to 3,4-disubstituted piperidines

A novel approach to 3-substituted 4-piperidinones is described. The one-pot tandem oxidation-cyclization-oxidation of unsaturated alcohols 1a-e by PCC or PCC and trifluoromethanesulfonic acid affords piperidinones 2a-e in good yield. Reduction of 2a-e by L-Selectride gives the corresponding cis 3,4-disubstituted piperidines with diastereomeric ratios of >99:1. By contrast, reduction of 2a-e by Al-isopropoxydiisobutylalane gives the trans products with diastereomeric ratios of up to 99:1.     

Synthesis of hydrophosphorylated fullerene under neutral conditions

[chemical reaction: see text]. A variety of phosphorous compounds such as secondary phosphines, phosphine oxides, phosphinates, and phosphonates undergo addition to [60]fullerene in DMSO/C6H5Cl without extraneous reagents to produce hydrophosphorylated fullerene derivatives in moderate to high yield.