Aminomethyl Polystyrene Resin Research Articles

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 Highly Diverse Purine-Hydroxyquinolinone Bisheterocycles

Solid-phase synthesis of bisheterocyclic compounds that contain purine and the 3-hydroxyquinolin-4(1H)-one skeleton connected with an aliphatic spacer of a different length/structure is described. The reaction sequence started from the primary amines immobilized on aminomethylated polystyrene resin equipped with an acid-labile linker (4-(4-formyl-3-methoxyphenoxy)butyric acid). After the arylation of amines with 2,6-dichloropurine via its C(6), purine N(9) was alkylated and subsequently the chlorine at purine C(2) was substituted with aliphatic diamines. The resulting terminal amino group was used as the starting point for the synthesis of 3-hydroxyquinolin-4(1H)-one precursors based on the acylation with 3-amino-4-(methoxycarbonyl)benzoic acid followed by the saponification of the methyl ester and esterification of the resulting carboxylic acid with various haloketones. The intermediates were cleaved from the resin, and their cyclization to the target purine-hydroxyquinolinone bisheterocycles was accomplished by heating in acetic or trifluoroacetic acid.

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.

ChemInform Abstract: Preparation and Application of Polymer-Grafted Ti-BINOL Complexes as Chiral Catalysts in the Enantioselective Addition of Diethylzinc to Aldehydes.

Abstract Enantiomeric BINOL has been anchored to aminomethylated polystyrene resin at the 3- and 3,3′-positions of BINOL respectively. The resulting functionalized polymers 4 and 7 have been used as chiral ligands in the Ti-catalytic enantioselective addition of diethylzinc to aldehydes. Compared with the homogeneous ligands 5 and 8 in the same reaction, the polymer-supported ligands 4 and 6 gave, in some cases, higher enantioselectivity. The conformational inflexibility of the ligands was analyzed to illustrate the results.

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.

2-Quinoxalinol salen ligands incorporated into functionalized resins for selective solid-phase extraction of copper(II)

In exploring selective extraction systems for use in environmental remediation or in metal scavenging agents for use in combinatorial chemistry, a novel reagent for the selective extraction of copper(II) has been developed. 2-Quinoxalinol salen ligands supported on an aminomethyl-polystyrene resin has been shown to efficiently and selectively extract copper(II) ions from organic solvents within 30 min under a variety of experimental conditions. Mild reducing conditions allow for metal ion recovery.

P-Nitromandelic Acid Linked Peptide Synthesis

p-Nitromandelic acid (Pnm) was used as a safety-catch linker for solid-phase synthesis of base-labile compounds of Boc/Bzl-protected depsipeptides. Thus, racemic Pnm protected with hexafluoroacetone (HFA-protected Pnm) was coupled with aminomethylated polystyrene resin (AM-resin) to give Pnm-AM-resin. Resin-supported depsipeptides 1 were then synthesized by the standard protocols for solid-phase peptide synthesis. The reduction of 1 with SnCl2/HCl followed by TFA treatment under microwave irradiation afforded depsipeptides 2 (purity: 18-82%; 13 examples).

The synthesis of supported proline-derived ligands and their application in asymmetric diethylzinc addition to aldehydes

Attachment of the proline-derived ligand 5 to two types of polymers, i.e. aminomethylated polystyrene resin and respectively MeO-PEG, was achieved via a succinyl linkage from the 4-hydroxy group. Both of the supported ligands ( 7 and 8) were proved to be highly active with good enantioselectivity (up to 90% ee) for the catalyzed asymmetric diethylzinc addition to aldehydes. The insoluble polymer-supported catalyst could be easily recovered and was reusable for several consecutive catalytic runs without significant loss in enantioselectivity.

Development of Self-Indicating Resin

Previously, we have reported the development and application of self-indicating resins (SIR), materials which can indicate presence or absence of amines in the reaction solution by the conspicuous color change of a phenolsulfophthalein type dye immobilized on resin beads [2a]. Although the functionality necessary for attaching the dye to the resins could be readily introduced by the Suzuki-Miyaura coupling during the synthesis of the SIR 1, this approach was only applicable to the dyes containing suitable functionality for the cross-coupling reaction. In this article we describe a new approach of immobilizing the indicating dyes onto the resin support. The dyes suitable for loading onto aminomethyl polystyrene (PS) resin were prepared by Friedel-Crafts reaction of 2-sulfoterephthalic anhydride with a wide range of phenols. Using this new route, the SIR 6c was readily prepared in >100g quantities. Use of the SIR 6c in the synthesis of a 144 member urea library was demonstrated and the SIR successfully indicated the endpoint of the reaction between amines and isocyanates.

Synthesis of polymer-bound 4-acetoxy-3-phenylbenzaldehyde derivatives: applications in solid-phase organic synthesis.

Aminomethyl polystyrene resin was reacted with 4-(5'-formyl-2'-hydroxyphenyl)benzoic acid and 4-(5'-formyl-2'-hydroxyphenyl)phenyl propionic acid, respectively, in the presence of 1-hydroxybenzotriazole and 1,3-diisopropylcarbodiimide to yield polymer-bound benzaldehydes. The phenolic group in resins was acetylated with acetic anhydride to afford two polymer-bound 4-acetoxybenzaldehydes. The reductive amination of polymer-bound linkers by amines and sodium triacetoxyborohydride, followed by sulfonylation with arylsulfonyl chloride derivatives in the presence of pyridine and the cleavage with TFA/DCM/H2O, produced pure sulfonamides.

Heterogeneous Baeyer–Villiger oxidation of ketones using hydrogen peroxide as oxidant catalyzed by aminomethyl polystyrene resin-supported tin complex

An aminomethyl polystyrene resin supported tin complex (PS–Sn) catalyst was prepared by a simple procedure and found to be an active and selective catalyst for the Baeyer–Villiger (B–V) oxidation of cyclic and acyclic ketones including 2-adamantanone, 2-methylcyclohexanone, cyclohexanone, 2- tert-butylcyclohexanone, 4- tert-butylcyclohexanone, 4-methylcyclohexanone, 3-methyl-2-pentanone, 4-methyl-2-pentanone, and cyclopentanone using 30% hydrogen peroxide as oxidant.

Combinatorial Solid-Phase Synthesis of 6-Hydroxy-1,2,3,4-tetrahydro-β-carbolines from l-5-Hydroxytryptophan

A library of biologically relevant 6-hydroxy-tetrahydro-beta-carbolines (6-OH-THBCs) based on the L-5-OH-tryptophan scaffold was prepared. A solid-phase synthesis was developed, utilizing aminomethyl polystyrene resin and solid-phase-optimized reactions, such as Pictet-Spengler condensation. The library was designed such that three points of diversity would be readily introduced, making the strategy potentially suitable for generation of a large number of compounds.

Preparation of Core−Shell-Type Aminomethyl Polystyrene Resin and Characterization of Its Functional Group Distribution

ADVERTISEMENT RETURN TO ISSUEPREVReportNEXTPreparation of Core−Shell-Type Aminomethyl Polystyrene Resin and Characterization of Its Functional Group DistributionTae-Kyung Lee, Sun-Jong Ryoo, Jang-Woong Byun, Sang-Myung Lee, and Yoon-Sik LeeView Author Information School of Chemical and Biological Engineering, Seoul National University, Seoul 151-742, Korea, and BeadTech Inc., Seoul National University Research Park, Suite 313, Seoul 151-818, Korea Cite this: J. Comb. Chem. 2005, 7, 2, 170–173Publication Date (Web):January 12, 2005Publication History Received13 August 2004Published online12 January 2005Published inissue 1 March 2005https://doi.org/10.1021/cc0498635Copyright © 2005 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views684Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (148 KB) SUBJECTS:Aromatic compounds,Fluorescence,Functional groups,Layers,Organic polymers Get e-Alerts

A novel class of chemically modified iodo-containing resins: design, synthesis and application to mass spectrometry-based proteome analysis.

A novel class of chemically modified iodo-containing resins with isotope-labeled tagging for mass spectrometry-based proteome analysis is described. This iodo-containing resin contains a thiol-reactive group that is used to capture the cysteine (Cys)-containing peptides from peptide mixtures, one 'tag' amino acid, and an aminomethyl polystyrene resin with Rink Amide Linker. The 'tag' amino acid is synthesized in both heavy and light isotope-coded forms and therefore permits the direct relative quantification of peptides/proteins through mass spectrometric analysis. In the iodo-containing resin strategy, the Cys-containing peptides of two samples covalently captured by either light or heavy iodo-containing resin were mixed and washed extensively under stringent conditions. Then the Cys-containing peptides were retrieved by acid-catalyzed elution. Finally, the eluted peptides were directly analyzed by micro liquid chromatography/mass spectrometry for identification and relative quantification. The iodo-containing resins were synthesized by a simple but effective method. Their abilities to identify and quantify the Cys-containing part in two samples were proved by the analysis of mixtures of amino acids, peptides and proteins.

Synthesis and conformational investigation of cyclic dipeptides: 7‐membered rings containing α‐ and β‐amino acids

The synthesis of heterocyclic compounds containing the 7-membered ring system [1,4]diazepane-2,5-dione is described. The aim of this study was to elaborate the solid phase and solution synthesis of eight representatives of the cyclic scaffold and to investigate their chemical stability and their conformational properties. The solid phase synthesis was performed on aminomethyl polystyrene resin using 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid as a backbone linker system (BAL-linker). After attachment of the alpha- and beta-amino acid and deprotection of the amino function, the dipeptide ester was obtained. The molecule was cyclized on the solid support by treatment with NaOMe in MeOH/NMP. The product was cleaved from the resin by TFA. For the solution pathway the linear dipeptides were synthesized by coupling of the BOC-protected L-alpha-amino acid with the beta2-amino acid ester (EDC/HOBT). After N- and C-terminal deprotection of the dipeptide, the linear species was cyclized with EDC/HOBT at a concentration of 3 mM in DMF. The products showed high chemical stability after storage in DMSO at room temperature for weeks. The x-ray and two dimensional NMR investigations were performed to investigate the conformation of the molecules. Three types of configuration could be distinguished by NMR, depending on the substitution pattern of the cyclic compounds. The x-ray results confirmed the NMR observations. In general the 7-membered rings showed rigidity, thus they could represent optimal scaffolds for new receptor ligands.

Synthesis of naphthoxylosides on solid support

In order to investigate the selective antiproliferative effects shown by 2-(6-hydroxynaphthyl)-β-d-xylopyranoside, the 14 possible β-d-xylopyranosidic compounds were synthesized on solid support. An aminomethylated polystyrene resin was converted into an acid chloride resin and then esterified using dihydroxynaphthalene. The free hydroxy group was then xylosylated under BF3·OEt2 mediated conditions. The xyloside was deprotected and simultaneously cleaved off the resin using NaOMe/MeOH. Final purification using reverse phase HPLC gave the pure xylosides in 6–42% yield with virtually no formation of α-xylosides.

Utilization of synergetic effect of weak interactions in the design of polymeric sorbents with high sorption selectivity

Cystine and tyrosine were used as model sorbates to illustrate the design of sorbents with high sorption selectivity using two types of weak interactions that act synergistically. When two types of weak interactions are the driving forces in a sorption and they act synergistically, the second interaction would be effectively intramolecular. The entropy lost for the second interaction should be lower than that for the same interaction that occurs alone, and thus a significant enhancement of sorption should result. We designed an N-acetyl aminomethyl polystyrene resin ( N-acetyl HC-D309), which was expected to sorb tyrosine through hydrophobic interaction and hydrogen bonding but not cystine. The chromatographic results for tyrosine and cystine indicate that the separation efficiencies on the N-acetyl HC-D309 column are higher than those on a styrene–divinylbenzene copolymer column, on which sorption should be driven by hydrophobic interaction only, and on an acrylamide- N, N′-methylene bisacrylamide copolymer column, on which sorption should be driven by hydrogen bonding only. Tyrosine as well as cystine had no retention at all on the acrylamide- N, N′-methylene bisacrylamide copolymer column, indicating the hydrogen bonding had little contribution to the sorption when it acted alone. The above results further indicate that hydrophobic interaction and hydrogen bonding contributed to the sorption of tyrosine on N-acetyl HC-D309 and they also acted synergistically. One of the conclusions of this paper is that some weak interactions which contribute little to the sorption when they act alone may contribute to the sorption when they act synergistically with other interactions.