Aminomethyl Polystyrene Research Articles

Photolabile ortho‐Nitro‐Benzyl Carbonate as an Amino Protecting Group for Stereocontrolled Synthesis of 2‐Amino‐2‐Deoxy‐β‐d‐Glycosides

AbstractTraditional amino protecting groups are often removed under harsh conditions or incompatible with other protecting groups, rendering the synthesis of complex 2‐amino‐2‐deoxy‐β‐d‐glycosides difficult. Here, we utilize the photolabile ortho‐nitrobenzyl carbonate (oNBC) as an amino protecting group for stereocontrolled synthesis of 2‐amino‐2‐deoxy‐β‐d‐glycosides. The gold(I)‐catalyzed glycosylation with per‐O‐oNBC‐protected 2‐N‐phthaloyl (Phth)‐2‐deoxy‐, 2‐N‐trichloroacetyl (TCA)‐2‐deoxy‐, and 2‐N‐oNBC‐2‐deoxy‐glycosyl ynenoates proceeded smoothly to provide 2‐amino‐2‐deoxy glycosides with exclusive β‐selectivities via the neighboring group participation (NGP) effect. Removal of the multiple O‐ and N‐oNBC protecting groups of 2‐amino‐2‐deoxy glycosides was achieved under irradiation at 365 nm with aminomethyl polystyrene as the carbonyl scavenger.

Adsorption of Pd(II) and Au(III) Ions by Commercial Tris(2-Aminoethyl) Amine Polystyrene Polymer Beads

Adsorption of gold and palladium species containing chlorine ion species onto commercial N-(2-[bis(2-aminoethyl)amino)ethyl]aminomethyl–polystyrene polymer beads (TRIS) was investigated. The influence of the pH, initial metal ion concentration, and contact time on the adsorption performance was examined in a batch adsorption experiment. To examine and discuss both the theoretical character of the metal ion adsorptions, Langmuir, modified Langmuir, Freundlich, Tempkin, Dubinin–Radushkevich, and nonlinear solutions of modified Langmuir and Redlich–Peterson isotherm models variables are calculated. The modified Langmuir monolayer adsorption capacities of the Pd(II) and Au(III) chlorine ions species were found to be 206.93 and 173.18 mg/g, respectively. The two metal adsorption kinetics fit the pseudo-second-order kinetic models. In thermodynamic calculations, the choice of different equilibrium constants with having a dimension is an important problem in the field. To overcome these problems, the modified Langmuir isotherm equilibrium constant was used for determination of thermodynamic parameters. Adsorption mechanism steps were characterized using Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). The adsorbent is made to interact with each metal ion in the HCl solution electrostatic interaction and surface complex formation between the amine groups. The calculation of the thermodynamic parameters using the dimensionless modified Langmuir equilibrium constant was found to be more satisfying and reliable. Adsorptions of Pd(II) and Au(III) on TRIS beads were exothermic and endothermic spontaneous processes, respectively.

Enzyme Immobilization and Optimization on Polymeric Nanospheres

Enzimler, pek çok endüstride kullanılan, maliyetleri oldukça yüksek olan önemli materyallerdir. Katalitik tepkimelerde enzimler için şartlar uygun olsa bile yüksek sıcaklık, yüksek veya düşük pH ve organik/inorganik çözücülerin varlığında enzimler aktifliklerini kolaylıkla kaybedebilirler. İmmobilizasyon işlemi ile birlikte, enzimlerin ekonomik açıdan kullanılabilirliğini sağlamak mümkündür. Bu amaçla, (aminometil) polistiren (APS) kaynaklı nanokürelere glukoz oksidaz (GOx) enzimi immobilize edildi ve optimizasyon parametreleri (pH, sıcaklık, tekrar kullanım sayısı, depolama kararlılığı, substrat derişimi) belirlendi. Serbest ve immobilize enzim için Michaelis-Menten eşitliği ile Km ve Vmak değerleri hesaplandı. Özellikle Pt(IV) iyonu içeren immobilize enzimin substratına karşı yüksek ilgi gösterdiği tespit edildi. 12 ay sonunda immobilize enzimlerin yaklaşık % 85 aktifliklerini korudukları görüldü.

Convenient method of peptide hydrazide synthesis using a new hydrazone resin

Peptide hydrazides can be easily synthesized using a new hydrazone resin, obtained via acylation of aminomethyl polystyrene by Fmoc-hydrazone of pyruvic acid. It was shown that the hydrazone linker is completely stable in the course of standard Fmoc SPPS. Moreover, it can tolerate a treatment with 5% TFA/DCM thus permitting selective removal of Mtt or related acid-labile protecting groups. Subsequent application of cleavage cocktails containing net TFA permits to obtain the desired peptides in a reasonable yields and purity. Synthesized peptide hydrazides can be applied as building blocks for the conjugation with different carrier molecules using hydrazone ligation technique.

Immobilization of glucose oxidase attached to new nanospheres including azomethine

New nanosphere supports were prepared and characterized for the immobilization of glucose oxidase from Aspergillus niger. Nanoparticles ((APS-tio), (APS-tioCH3), and (APS-tioCl)) modified (aminomethyl)polystyrene (APS) with some tyophenealdehyde derivatives were synthesized by means of condensation and we investigated the enzymatic properties of glucose oxidase enzyme (GOx) immobilized on them. Modified polystyrene was characterized by IR spectra, gel permeation chromatography and scanning electron microscopy. Immobilized GOx on (APS-tioCH3) showed a optimum pH, whereas immobilized GOx on (APS-tio) and (APS-tioCl) performed the optimum condition at two pHs.

Influence of load on the recycling stability of nanospheres attached platinium ion for determination of glucose

New nanospheres have been prepared with Pt2+ and Pt4+ for compare enzymatic properties of glucose oxidase enzyme (GOx). In this study nanoparticles, (aminomethyl)polystyrene (APS), 2-hydroxy-5-methylbenzaldehyde and Pt2+/Pt4+ have been synthesized by means of template and investigated the enzymatic properties of glucose oxidase enzyme (GOx) immobilized on there. The characteristics of the immobilized glucose oxidase (APS–Pt2+–GOx and APS–Pt4+–GOx) enzyme showed one optimum pH value. The influence of temperature, reusability and storage capacity on the free and immobilized glucose oxidase enzyme have been investigated. It is found that nanosphere including platinium atom exhibits excellent performance as the immobilized supporter of GOx, the immobilized enzyme demonstrates perfected storage and recycling stability. APS–Pt2+–GOx retains more than 30% of the initial activity after 32 successive cycles, which is a remarkable result.

A Resin‐Linker‐Vector Approach to Radiopharmaceuticals Containing 18F: Application in the Synthesis of O‐(2‐[18F]‐Fluoroethyl)‐L‐tyrosine

A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide (18)F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [(18)F]-fluoride ion. Three model linker-vector molecules 7a-c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8a-c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy. On fluoridolysis, the RLVs 8a,b containing the longer spacers were shown to be more effective in the release of the fluorinated model vector (4-fluorobutyl)phenylcarbamic acid tert-butyl ester (9) in NMR kinetic studies and gave superior radiochemical yields (RCY≈60%) of the (18) F-labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O-(2-[(18)F]-fluoroethyl)-L-tyrosine ([(18) F]-FET), delivering protected [(18) F]-FET in >90% RCY. Acid deprotection gave [(18)F]-FET in an overall RCY of 41% from the RLV.

Controllable Core–Shell-Type Resin for Solid-Phase Peptide Synthesis

A simple, mild, and inexpensive biphasic functionalization approach is attempted for preparing an ideal core-shell-type resin. The core-shell-type architecture was constructed by coupling Fmoc-OSu to the amino groups on the shell layer of an aminomethyl polystyrene (AM PS) resin. The shell layer thickness of the resin could be easily controlled under mild conditions, which was characterized by confocal laser scanning microscopy (CLSM). The efficiency of core-shell-type resin for solid-phase peptide synthesis (SPPS) was demonstrated by the synthesis of various peptides and compared with commercially available noncore-shell-type resins such as AM PS and poly(ethylene glycol)-based resins. The core-shell-type resin provided effective performance during the synthesis of hydrophobic peptide sequences, a disulfide-bridged cyclic peptide, and a difficult PNA sequence. Furthermore, a highly aggregative peptide fragment, MoPrP 105-125, was synthesized more efficiently on the core-shell-type resin under microwave conditions than AM PS and ChemMatrix resins.

An improved procedure for the preparation of aminomethyl polystyrene resin and its use in solid phase (peptide) synthesis

2-Aminoethanol was used to successively replace hydrazine in the preparation of aminomethyl polystyrene resin thereby facilitating purification and by-product removal. The syntheses of the polypeptides ACP (65–74) and oxytocin demonstrated that the use of aminomethyl polystyrene resin prepared in this manner was equal to or better than that prepared using the hydrazine method.

Solid‐Phase Synthesis of (Poly)phosphorylated Nucleosides and Conjugates

Succinyl-cycloSal-phosphate triesters of ribo- and 2'-deoxyribonucleosides were attached to aminomethyl polystyrene as an insoluble solid support and reacted with phosphate-containing nucleophiles yielding nucleoside di- and triphosphates, nucleoside diphosphate sugars, and dinucleoside polyphosphates in high purity after cleavage from the solid support. Here, reactive cycloSal-phosphate triesters were used as immobilized reagents that led to a generally applicable method for the efficient synthesis of phosphorylated biomolecules and phosphate-bridged bioconjugates.

Versatile Solid Supports for Oligonucleotide Synthesis that Incorporate Urea Bridge

The universal solid support, USIII, representing a new and improved version of commercial USII, as well as 2 ′-deoxynucleoside and 2 ′-deoxy-2 ′-fluoronucleoside bound supports, incorporating a labile phenoxyacetyl fragment, was synthesized by an aminomethyl polystyrene carbamoylation with corresponding azides in the presence of aqueous triethylammonium bicarbonate. All three solid phases incorporate a stable urea tether, thus bridging the polymer and functional linker. These new matrices proved to be potent solid phases for the synthesis of DNA, RNA, or modified oligonucleotides as well as randomized mixed 2 ′-ribo/2 ′-deoxy-2 ′-fluoro-RNA libraries and/or DNA libraries, randomized with trinucleotides (codons).

Synthesis and Characterization of Polystyrene Supported Catalytically Active Poly(amidoamine) Dendrimer-Palladium Nanoparticle Conjugates

Poly(amidoamine) dendrimers were synthesized on cross-linked aminomethyl polystyrene. Palladium complexes of supported dendrimers prepared by ligand exchange method were reduced to dendrimer-nanoparticle conjugates supported on polystyrene resin. The supported nanoparticles were used as heterogeneous catalysts for the Suzuki coupling between aryl boronic acids and aryl halides. Various factors affecting the catalysts performance were studied. Higher generation dendrimers gave well-defined nanoparticles without agglomeration and these particles showed good catalytic performance.

ChemInform Abstract: Polymer-Supported BINOL Ligand for the Titanium-Catalyzed Diethylzinc Addition to Aldehydes: A Remarkable Positive Influence of the Support on the Enantioselectivity of the Catalyst.

A new polymer-supported BINOL (1,1‘-Bi-2-naphthol) was synthesized by coupling of aminomethyl polystyrene resin and (S)-2,2‘-dihydroxy-1,1‘-binaphthyl-3,3‘-dicarboxylic acid. This new ligand was found to be more enantioselective for the asymmetric addition of diethylzinc to aldehydes than its “free” analog [Ti(BINOL)iPrO2]. A range of 57−99% ee's as well as 78−97% yields was obtained, and the electronic properties of the enantioselectivity were also observed.

Solid-phase synthesis of 5′-O-β,γ-methylenetriphosphate derivatives of nucleosides and evaluation of their inhibitory activity against HIV-1 reverse transcriptase

Bis(dichlorophosphino)methane was converted to a β,γ-methylenetriphosphitylating reagent. The reagent was immobilized on aminomethyl polystyrene resin-bound linker of 4-acetoxy-3-phenylbenzyl alcohol to afford a polymer-bound β,γ-methylenetriphosphitylating reagent, which was reacted with unprotected nucleosides followed by oxidation with tert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and acidic cleavage, to produce 5'-O-β,γ-methylene triphosphate nucleosides in 53-82% overall yields. Among all the compounds, cytidine 5'-O-β,γ-methylenetriphosphate inhibited completely RNase H activity of HIV-1 reverse transcriptase at 700 μM.

Synthesis and Chelating Properties of Polystyrene Supported Schiff Base (N,N′-disalicylidenepropylenetriamine) Resin Toward Some Divalent Metal Ions

A new polystyrene-supported Schiff base resin, N,N-bis(salicylidenepropylenetriamine)- aminomethyl polystyrene, has been synthesized through a reaction between the commercially available 4-chloromethyl polystyrene polymer and the Schiff base, N,N′-disalicylidenepropylenetriamine. The chelation behavior of this resin toward the divalent metal ions Cu2 +, Ni2 +, Zn2 +, and Pb2 + in aqueous solutions was investigated. Batch equilibration experiments were carried out as a function of contact time, pH, amount of metal-ion, polymer mass, and temperature. The amount of metal-ion uptake of the polymers was determined by using atomic absorption spectrometry (AAS). Results of the study revealed that the resin exhibited higher capacities and a more pronounced adsorption toward Cu2 + and that the metal-ion uptake follows the order: Cu2 + > Zn 2 + > Ni2 + > Pb2+. The adsorption and binding capacity of the resin toward the various metal ions investigated are discussed.

Solid-Phase Synthesis of Peptidyl Thioacids Employing a 9-Fluorenylmethyl Thioester-Based Linker in Conjunction with Boc Chemistry

A method for the synthesis of peptidyl thioacids is described on the basis of the use of the N-[9-(thiomethyl)-9H-fluoren-2-yl]succinamic acid and cross-linked aminomethyl polystyrene resin. The method employs standard Boc chemistry SPPS techniques in conjunction with 9-fluorenylmethyloxycarbonyl protection of side-chain alcohols and amines and 9-fluorenylmethyl protection of side-chain acids and thiols. Cleavage from the resin is accomplished with piperidine, which also serves to remove the side-chain protection and avoids the HF conditions usually associated with the resin cleavage stage of Boc chemistry SPPS. The so-obtained thioacids are converted to simple thioesters in high yield by standard alkylation according to well-established methods.

Enantioselective Synthesis of N-Protected α-Amino Acid Hydrazides

A new, mild, general, and efficient synthesis of N-protected α-amino acid hydrazides is described. This two-step preparation uses N-aminophthalimide as protected hydrazine to prepare N-protected α-amino acid hydrazide precursors, and subsequent de­phthaloylation with an aminomethyl polystyrene resin yields N-protected α-amino acid hydrazides. It has the advantages of avoiding the use of the toxic hydrazine reagent and being compatible with the most commonly used N-protecting groups. This strategy is particularly interesting in the case of N-(9-fluorenylmethoxycarbonyl)-protected amino acids. Within the limits of chiral HPLC detection, no epimerization is apparent.

The Influence of Pore Structures and Degree of Crosslinking on Catalytic Properties of Aminomethyl Polystyrene Resins Supported Dendritic Sn Complexes

Seven different aminomethyl polystyrene resins supported dendritic Sn complexes were prepared by solid phase synthesis methodology. All the synthesized complexes show promising catalytic activities for the Baeyer‐Villiger oxidation of ketones with hydrogen peroxide and affording the corresponding lactones or esters. The influence of different pore structures and the degree of crosslinking of the aminomethyl polystyrene resins on catalytic properties of the supported dendritic Sn complexes were well discussed.

Solid-Phase Synthesis of Symmetrical 5‘,5‘-Dinucleoside Mono-, Di-, Tri-, and Tetraphosphodiesters

Four classes of phosphitylating reagents were subjected to reactions with aminomethyl polystyrene resin-bound p-acetoxybenzyl alcohol to yield the corresponding polymer-bound mono-, di-, tri-, and tetraphosphitylating reagents. The solid-phase reagents were reacted with unprotected nucleosides (e.g., thymidine, adenosine, 3'-azido-3'-deoxythymidine, cytidine, or inosine) in the presence of 5-(ethylthio)-1H-tetrazole. Polymer-bound nucleosides underwent oxidation with tert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford 5',5'-dinucleoside mono-, di-, tri-, and tetraphosphodiesters in 59-78% yield.

Toward Improved Syntheses of Dendrimer-Based Magnetic Resonance Imaging Contrast Agents: New Bifunctional Diethylenetriaminepentaacetic Acid Ligands and Nonaqueous Conjugation Chemistry

Two different fourth-generation (G4) polyaminonamido dendrimer-based magnetic resonsance (MR) agents were prepared by a new synthetic approach wherein tert-butyl-protected forms of 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriamine pentaacetic acid (1B4M-DTPA), bearing either an isothiocyanate or a succinimidyl ester moiety, respectively, were conjugated to the primary amines of the dendrimer. Purification was facilitated using a solid phase, N-(2-aminoethyl)aminomethyl polystyrene. After Gd(III) incorporation, molar relaxivity measurements of both new dendrimer-based agents as compared to a G4 agent prepared by an aqueous chemistry route indicated no significant changes in relaxivity. Comparative MR imaging revealed equivalent enhancement of the vessels and organs such as the kidney and liver, although slightly different vascular clearance rates were observed. This general synthesis provides a procedure for preparation of dendrimer-based MR agents for clinical applications with higher yields and efficiency while enhancing versatility. The latter aspect is further demonstrated by preparation of a novel maleimide analog of 1B4M-DTPA from a key synthetic intermediate aniline derivative.