Solid-phase Resin Research Articles

Neurotrophic peptide aldehydes: Solid phase synthesis of fellutamide B and a simplified analog

A combination of solid phase and solution phase synthetic methods have been used to complete the total synthesis of the neurotrophic lipopeptide aldehyde fellutamide B ( 2). The β-hydroxy aliphatic tail was prepared by regioselective reductive opening of a cyclic sulfate, and later coupled to a solid phase resin. The synthetic compound was then examined in cytotoxicity and nerve growth factor (NGF) induction assays. A simplified analog of fellutamide B also showed activity.

Study of trace metal partitioning between soil–EDTA extracts and Chelex-100 resin

The partitioning of Cu, Cd and Pb in EDTA leachates from a variety of soils, to Chelex-100 resin was investigated. A series of experiments was conducted to optimise method for the trace element sorption on Chelex-100 in 13 unpolluted soils from Burgundy, France. The extraction efficiency of Chelex-100 varied depending on soil carbonate contents. The largest percentage of trace metals was transferred to the resin in non-calcareous samples, while the resin was used in its Ca form. This technique was able to trap up to 98% of Cu, 72% of Cd and 28% of Pb in non-calcareous soil leachates. The fraction of metal transferred to the Chelex-100 in calcareous soil extracts was 40% less than those in non-calcareous ones. Besides, a kinetic procedure was developed to study the kinetic of cation exchange from soil–EDTA leachates onto solid-phase resin. The soil calcium content was found to be a controlling factor in the Cu sorption on the Ca–Chelex. Two different kinetic behaviours were observed in calcareous and non-calcareous soils. The dissociation rate of Cu in non-calcareous soil extracts was 10 times higher than that in calcareous ones. Application of kinetic model indicated the presence of two components associated to Cu in non-calcareous samples. This was discussed in terms of metal sorption mechanism from soil solution onto chelating resin.

Magnetic Nanoparticles as an Orthogonal Support of Polymer Resins: Applications to Solid-Phase Suzuki Cross-Coupling Reactions

[reaction: see text] Most of the reactants immobilized on conventional solid-phase resins are buried inside the interiors of lightly cross-linked polystyrene beads. An orthogonal support of solid-phase resins needs to be small enough to penetrate the interpolymeric chain spaces of a swollen resin to reach reaction sites. In this paper, we report the use of magnetic nanoparticles ( approximately 4 nm) as an orthogonal matrix to assist solid-phase reactions. A magnetic nanoparticle-supported homogeneous Pd catalyst was employed for promoting the Suzuki cross-coupling of an aryl halide on resins and an excessive arylboronic acid in solution. The workup separating three components (the catalyst, product, and remaining arylborate) is a chromatography-free process. The Pd catalyst was magnetically isolated and recycled from the reaction mixture by applying an external magnetic field. Then, a filtration process was followed to recover the excess borate reagent from the resins/product. Our work here presents the first example of an orthogonal matrix of solid-phase resins and shows the promise of employing nanomaterials in organic synthesis.

Detection of human neutrophil elastase with peptide‐bound cross‐linked ethoxylate acrylate resin analogs

An assessment of elastase-substrate kinetics and adsorption at the solid-liquid interface of peptide-bound resin was made in an approach to the solid-phase detection of human neutrophil elastase (HNE), which is found in high concentration in chronic wound fluid. N-succinyl-alanine-alanine-proline-valine-p-nitroanilide (suc-Ala-Ala-Pro-Val-pNA), a chromogenic HNE substrate, was attached to glycine-cross-linked ethoxylate acrylate resins (Gly-CLEAR) by a carbodiimide reaction. To assess the enzyme-substrate reaction in a two-phase system, the kinetic profile of resin-bound peptide substrate hydrolysis by HNE was obtained. A glycine and di-glycine spacer was placed between the resin polymer and substrate to assess the steric and spatial requirements of resin to substrate with enzyme hydrolysis. The enzymatic activities of suc-Ala-Ala-Pro-Val-pNA and suc-Ala-Ala-Pro-Ala-pNA on the solid-phase resin were compared with similar analogs in solution. An increase in visible wavelength absorbance was observed with increasing amounts of substrate-resin and enzyme concentration. Enzyme hydrolysis of the resin-bound substrate was also demonstrated on a polypropylene surface, which was employed for visible absorbance of released chromophore. A soluble active substrate analog was released from the resin through saponification of the ethoxylate ester linkages in the resin polymer. The resin-released conjugate of the HNE substrate demonstrated an increased dose response with increasing enzyme concentration. The synthesis and assay of elastase substrates bound to CLEAR resin gives an understanding of substrate-elastase adsorption and activity at the resin's solid-liquid interface for HNE detection with a solid-phase peptide.

Synthetic applications of aryl radical building blocks for cyclisation onto azoles

2-(2-Bromophenyl)ethyl groups have been used as building blocks in radical cyclisation reactions onto azoles to synthesise tri- and tetra-cyclic heterocycles. 2-(2-Bromophenyl)ethyl methanesulfonate was used to alkylate azoles (imidazoles, pyrroles, indoles and pyrazoles) for the synthesis of the radical precursors. Cyclisations of the intermediate aryl radicals yield new 6-membered rings attached to the azoles. The aryl radicals undergo intramolecular homolytic aromatic substitution onto the azole rings. Tributylgermanium hydride has been used with success to replace the toxic and troublesome tributyltin hydride. Initial studies show that the protocol can be used on solid phase resins. The molecular and crystal structures of methyl 5,6-dihydroimidazo[5,1- a]iso-quinoline-1-carboxylate and methyl 5,6-dihydroimidazo[2,1- a]isoquinoline-3-carboxylate were determined by X-ray crystallography.

Use of fluorous and solid-phase electrophiles as scavengers for excess amine in the preparation of sulfur-35 labelled radioligands

A method for scavenging excess amines in sulfur-35-labeled radioligand preparations using fluorous scavengers has been developed in an effort to simplify the purification. This fluorous scavenging has been shown to be effective at removing excess amines from several [35S]sulfonylation mixtures. In many cases this results in one less semi-preparative HPLC purification, and thus in higher radiochemical yield and time savings. Fluorous scavenging was compared to the use of a solid-phase resin (PS-isocyanate) and determined to be approximately equal with respect to recovery of radioactive product. However, the fluorous scavengers were shown to be more effective than solid-phase resin for removing basic amine components. Copyright © 2005 John Wiley & Sons, Ltd.

Pressurized Liquid Extraction of Bioactive Compounds from Taiwan Pines

An experiment combining the Taguchi methodology with the response surface methodology to optimize the Pressurized Liquid Extraction (PLE) of proanthocyanidins from Taiwan pines was conducted. A L18 orthogonal array was selected to investigate the total yield and the amount of proanthocyanidins. Experimental results showed that the extraction temperature most significantly affected the efficiency of extraction, but that a higher temperature also caused decomposition of bioactive components. Optimum conditions were identified as 20% EtOH, 140℃,750 psig, and 1.5h. The PLE total yield, proanthocyanidins content and total flavonoids were 2.09, 2.07, and 2.01 times greater than those obtained using a 50% EtOH conventional extraction method. Hot pressurized extraction has the advantages of low energy and high yield of bioactive compounds. The antioxidant activities of several extracts from two Taiwan pine-needles were individually evaluated for scavenging of DPPH free radicals and superoxide anion radicals, and for the inhibition of lipid peroxidation. The results revealed that both PLE M (Pinus morrisonicola) and PLE T (Pinus taiwanensis) extracted from two fresh pine needles scavenged 78.91% of DPPH free radicals. Air-dried pine needles also strongly inhibited superoxide anion radicals. The purification of four anthocyanidins from a PLE T extract was initially tested using HP-20 resin solid phase extraction and showed little enhancement. The isolation, purification and antioxidative mechanism of active components from pine needles need to be further investigated.

Multisyringe flow injection analysis of stable and radioactive strontium in samples of environmental interest

A multisyringe flow injection (MSFIA) method for the determination of stable and radioactive strontium, using a solid phase resin (Sr-Resin), has been developed. Strontium concentrations are determined by atomic emission spectroscopy and by a low background proportional counter. The method has been applied to different samples (water, milk and soil) of environmental interest. The LLD of the stable and radioactive Sr were 10 μg/l and 0.01 Bq, respectively. The standard deviation of the separation procedure is 2% ( n=10).

Dynamic kinetic resolution (DKR) using immobilized amine nucleophiles

The first example of a dynamic kinetic resolution (DKR) using immobilized amine nucleophiles is described. This approach utilizes a nucleophilic amine attached to a solid phase resin via an organic spacer. The optical purities of the N-substituted α-amino ester products are superior to the solution phase DKR with diastereomeric ratios ranging from 11:1 to 18:1 and chemical yields between 66% and 98%.

Solid-Phase Assisted N-1 Functionalization of Azamacrocycles

A simple solid-phase assisted strategy for the N-1 functionalization of azamacrocycles is described. Compounds such as cyclen, cyclam and piperazine can be selectively modified by temporary attachment to solid-phase resins providing an efficient and clean method to prepare biomedically interesting moieteies.

Isolation of phosphopeptides using solid phase enrichment

Protein phosphorylations are post-translational protein modifications that are crucial for intercellular signal transduction and the regulation of many cellular events. We describe herein a novel technology utilizing α-diazo functionalized solid phase resins to isolate phosphorylated peptides from non-phosphorylated substrates.

Determination of Clopidol Residues in Chicken Tissues by Liquid Chromatography: Collaborative Study

Eighteen laboratories participated in a collaborative study on the determination of clopidol residues in chicken muscle tissues by liquid chromatography. Of these, results from 16 laboratories which rigorously followed the method were subjected to statistical analysis. The method performance was assessed by all participants using 14 samples of chicken muscle fortified at concentrations ranging from 0.1 to 5.0 mg/kg. In addition, 9 participants each reported results for 6 clopidol-incurred samples in chicken muscle. Test portions were extracted with acetonitrile, and the extracts were purified with alumina and anion exchange resin solid-phase extraction cartridges in sequence. Clopidol was separated by reversed-phase liquid chromatography and quantified at 270 nm. Average recoveries ranged from 81.8 to 85.4%, reproducibility relative standard deviation (RSDR) ranged from 11.9 to 22.6%, and repeatability relative standard deviation (RSDr) ranged from 9.9 to 15.1%. For clopidol-incurred samples at concentrations of 0.100-0.687 mg/kg, the mean determination value range was 0.099-0.659 mg/kg; RSDR was 12.6-19.8%, RSDr was 3.1-8.5%; and HORRAT values were 0.7-1.1. The accuracy and precision of the method are in conformity with the requirements specified by AOAC INTERNATIONAL. The method was adopted Official First Action in April 2003.

Chemoenzymatic route to macrocyclic hybrid peptide/polyketide-like molecules.

Hybrid peptide-polyketides are a class of medically and biologically important natural products characterized by stereochemical and functional diversity. In their biosynthesis, hybrids are often macrocyclized to achieve rigid structures that populate bioactive conformations. We herein present a chemoenzymatic strategy to access the stereochemical and functional diversity found in macrocyclic hybrid natural products in a manner amenable to efficient library synthesis. Our method makes use of small building blocks in the form of Fmoc-protected epsilon-amino acids containing embedded polyketide functionality. The building block approach allows for combinatorial synthesis of linear molecules that can be activated as soluble thioesters or tethered to a solid-phase resin. We demonstrate that these linear molecules are substrates for macrocyclization by a tolerant catalyst, TycC TE, derived from a nonribosomal peptide synthetase. The method should allow for access to diverse structures with hybrid peptide-polyketide character that can be screened for improved or novel activities.

Reagent concentration effects in the REM resin solid phase synthesis of tertiary amines

The use of reagent concentration has resulted in increased rates for all stages of the REM resin synthesis of tertiary amines. These increases in rate translate into faster reaction times, higher yields and lower reagent consumption. Of the methods examined, the most successful was the use of perfluorous solvents, either alone or with a small amount of organic co-solvent.

Synthesis of Functionalized 1,5‐Cyclooctadienes by LICKOR Metalation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Modern Separation Techniques for the Efficient Workup in Organic Synthesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Solid-Phase Synthetic Strategy for Labeled Peptides: Synthesis of a Biotinylated Derivative of the δ Opioid Receptor Antagonist TIPP (Tyr-Tic-Phe-Phe-OH)

A general solid-phase synthetic strategy for labeled peptides was developed and used to prepare a biotinylated derivative of the delta opioid receptor antagonist TIPP (Tyr-Tic-Phe-Phe-OH). A monoprotected hydrophilic diamine linker was attached to an aldehyde-containing solid-phase resin by reductive amination, followed by introduction of biotin and peptide synthesis to yield Tyr-Tic-Phe-Phe-Asp-NH(CH(2)CH(2)O)(2)CH(2)CH(2)NH-biotin (2). The high delta receptor affinity and selectivity of 2 demonstrate the applicability of this design approach for labeled peptide derivatives.

Wavelength dependent photo-controlled differential release of compounds from solid phase resin.

A method to effect photo-mediated differential release of bead-based compound libraries using a tuneable laser in combination with chromatically orthogonal photolabile linkers is described.

Recycling solid supports--a head-to-tail linker.

The concept of a 'head-to-tail linker' designed to allow the regeneration and reuse of a variety of solid supports is introduced. The synthesis of this linker, its coupling to various solid supports, its application in a number of standard solid phase reactions and resin regeneration are presented.

Solid Phase Synthesis of 1,2-Disubstituted Alkenes: A Novel Alkynyldihydropyridine to Alkenylpyridine Isomerization

A series of 1,2-disubstituted pyridylalkenes have been prepared using a solid-phase resin approach. This approach takes advantage of a novel alkynyldihydropyridine to alkenylpyridine isomerization.