Micelle-derived polymer supports for enantioselective catalysts

The BINOL moieties are successfully immobilized on the surface of a micelle-derived polymer. Ti-BINOLate complexes prepared from the polymer with Ti(O-i-Pr)₄ exhibited high catalytic activity for the asymmetric alkylation of benzaldehyde with Et₂Zn to afford the adduct in up to 96% yield with 84% ee.     

PEG-related polymer resins as synthetic supports

Combinatorial chemistry has become a significant part of the discovery and optimization process for novel drugs, affinity ligands, and catalysts. The polymeric supports play a key role in combinatory chemistry. Therefore, various kinds of functional polymer resins have been exploited as supports, reagents, and catalysts in organic synthesis. In comparison to the conventional Merrifield resins, the poly(ethylene glycol) (PEG)-related polymer resins have advantages including good compatibilities with polar solvents, good solvent absorbency and swelling properties. This review focuses primarily on the more recent work in the field of developing PEG-related polymer resins as supports for organic synthesis.     

PEG化的聚合物载体树脂研究进展

组合化学已成为发现和优化新药、亲和配体和催化过程中的重要组成部分.高分子载体树脂在组合化学中起着关键的作用,各种类型的聚合物树脂在有机合成中已被广泛开发为载体、反应物和催化剂.与传统的Merrifield树脂相比较,聚乙二醇(PEG)化的聚合物树脂具有与极性溶剂更好的相容性、更高的溶剂吸收和溶胀性能.本文主要综述与PEG相关联的聚合物树脂在有机合成载体领域中的最新成果.     

Reactivity of ester groups on insoluble polymer supports

A study was made of the comparative rates of reaction of active ester functional groups (p-nitrophenyl and 2,4-dinitrophenyl esters) situated on three types of insoluble support polymers and on small, soluble analogs of the polymer molecules. The supports consisted of a styrene—divinylbenzene bead-type polymer (2% DVB), a styrene—divinylbenzene popcorn polymer (0.2% DVB), and a popcorn polymer with 2,3-dimethylbutadiene and substituted styrene units in the chain. p-Nitrophenyl benzoate and 2,4-dinitrophenyl p-isopropylbenzoate were used as soluble analogs. Rates of aminolysis by small molecules (2-aminoethanol and n-tetradecylamine) in pyridine and of solvolysis in alcohols catalyzed by both small (N-methylimidazole) and large (polyvinylimidazole) molecules were determined. With the small amines, finely divided particles of popcorn and bead type styrene polymers reacted at about the same rate, which was approximately 1/5 the rate of reaction of the homogeneous analogs. With a high molecular weight reagent, polyvinylimidazole, the heterogeneous reactions were much slower and the popcorn polymer reacted faster than the bead polymer. In catalyzed solvolyses, the styrene popcorn derivative reacted faster in benzyl alcohol and slower in 1-hexanol than the dimethylbutadiene popcorn polymer derivatives.     

Development of new hydrophilic polymer supports based on dimethylacrylamide

A survey of the development of hydrophilic resins based on dimethylacrylamide (DMA) is presented. It describes the preparation of DMA-based resins by suspension copolymerization of DMA and acrylamide-based crosslinking and functional monomers. Swellability data for a number of DMA-based resins are tabulated, demonstrating that the resins swell to approximately the same extent in dichloromethane as they do in water, methanol, dimethylformamide or dimethylsulphoxide, but they swell only slightly or not at all in tetrahydrofuran. Typical chemical reactions employed for quantitative estimation or derivatization of resin-bound functional groups, including those involving intra-resin crosslinking, are discussed. The development of composite polymer supports, in which the DMA-based polymer is supported on kieselguhr particles or an amphiphilic ion exchange polymer is supported on DMA-based resin beads, is also covered briefly.     

硅胶表面替米考星分子印迹聚合物的制备

表面印迹接枝技术即在硅胶表面或有机聚合物载体表面[1]、毛细管表面[2]进行接枝聚合并引进分子印迹的技术[3-6]。替米考星(Tilm icosin)是一种由泰乐菌素半合成的大环内脂类畜禽专用抗生素。本文以替米考星为模板分子,以甲苯为溶剂,以甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸     

Photochemistry on soluble polymer supports: synthesis of nucleosides

[reaction: see text] A new soluble polymer support synthesis of nucleosides is described. The photochemical ring expansion of cyclobutanones in the presence of poly(ethylene glycol) (PEG) results in polymer-supported ribosides. These photoadducts can be cleaved from the polymer under Vorbrüggen coupling conditions with TMS-protected purines and pyrimidines to give ribonucleosides. The method has been extended to include modified PEGs with dendritic end-groups in order to improve the loading levels for these coupling reactions.     

Chiral beta-cyclodextrin-based polymer supports prepared via ring-opening metathesis graft-polymerization

A series of norborn-2-ene-derivatized beta-cyclodextrins (beta-CDs), 6-O-(norborn-2-ene-5-carboxyl)-beta-CD (1), tetrakis(6-O-norborn-2-ene-5-carboxyl)-beta-CD (2), (3), 6-O-(6-norborn-2-ene-5-car-6-O-(7-oxanorborn-2-ene-5-carboxyl)-beta-CD bonylaminohexoyl)-beta-CD (4), 6-O-(norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (5), tris(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (6), tetrakis(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (7) and hexakis(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (8), have been synthesized. Compounds 1-3 were prepared via reaction of beta-CD with norborn-2-ene-5-carboxylic chloride and 7-oxanorborn-2-ene-5-carboxylic chloride, respectively; compounds 5-8 were synthesized from norborn-2-ene-5-yl-methyldichlorosilane and beta-CD, respectively. Compound 4 was accessible by reaction of norbom-2-ene-5-carboxylaminohexoyl chloride with beta-CD. Compounds 1-8 were surface grafted onto norborn-2-ene-derivatized silica-based supports using ring-opening metathesis polymerization employing the ruthenium-based initiator bis(tricyclohexylphosphino)benzylideneruthenium dichloride [Cl2Ru(CHC6H5)(PCy3)2, Cy=cyclohexyl, 9]. Generally speaking, the resulting chiral stationary phases (CSPs) I-VIII may be prepared with high reproducibility and may be used within a pH of 2-10. Thus, relative standard deviations (sigman-1) of the mean resolution (Rs) are <7%. The CSPs were used for the enantioselective separation of beta-blockers, N-dansyl-, N-3,5-dinitrobenzoyl- and Fmoc-protected amino acids and were characterized in terms of chemical stability, selectivity (alpha') and resolution (Rs). Additionally, the role of the spacer as well as influences of capacity and the degree of substitution of the beta-CD moiety on the separation characteristics were determined.     

"Inverse" synthesis of polymer bioconjugates using soluble supports

Well-defined cleavable or non-cleavable soluble polystyrene supports were prepared by atom transfer radical polymerization and utilized for the iterative synthesis of functional hexapeptides. This approach allowed rapid and efficient liquid phase synthesis of peptide-polymer conjugates.     

Synthesis and investigation of novel branched PEG-based soluble polymer supports

The efficient synthesis of a number of novel poly(ethylene glycol)-based branched soluble polymer supports with high loading capacities has been developed. These compounds are characterized and tested for their loading levels utilizing a number of coupling reactions.     

The topochemistry of the catalytic systems on the surface of polymer supports

The method of spin labels based on stable iminoxyl radicals has been applied to the investigation of the topochemistry of polymer-supported polyethylene-grafting diallylamine (PE-gr-PDAA)and ofimmobilized catalytic systetms. The effective distances between fixed radicals are comparatively large (r? ～ 25-35Å for the case of functional groups of PE-gr-PDAA and r? ≥ 35Å for the case of fixed components of the catalytic systems). The demonstration of step-by-step penetration of the label into the functional cover (100-300 Å) has been made. Correlation times were calculated in the temperature range 290-440K. The dependence of log τ_c on 1/T shows two linear parts to the curve.The activation energies in the α region for PE-gr-PDAA and for the product of its interaction with TiCl₄. Ti(OC₄H₉)₄, and Al(C₂H₅)₂Cl are equal to 13, 14, 24, and 13 Kcal/mole, respectively. The method has been applied to the investigation of Ziegler-Natta immobilized catalytic systems. It has been noted that the labels are fixed not far from each other (r? ≤ 12Å) after the interaction of the catalytic components.     

Cross-linked and chemically functionalized polymer supports by reactive reversal nanoimprint lithography

A new format of polymer support having cross-linked polymeric micro- and nanoarrays has been fabricated via reactive reversal nanoimprint lithography. Reactive reversal nanoimprint lithography is a relatively simple method to imprint highly cross-linked and chemically tunable polymers. An array of chloromethyl-functionalized cross-linked polystyrene has been imprinted on hard (silicon) and soft (polymer) substrates, and a model esterification reaction is demonstrated. The imprints have been found to be relatively stable under both static and dynamic stability tests carried out in various organic solvents. The chemical functionality is evenly distributed over the imprinted array. This method of fabricating polymer supports offers a high degree of freedom in terms of the choice of chemical functionality, the types of polymer matrix, and the size of the polymer support. The functional polymer support has potential applications for chemical and biological assays.     

可溶性聚合物在有机合成中的应用研究

概述了液相合成中所使用的可溶性聚合物性质、类型、特点,以及可溶性聚合物在合成肽、低聚苷酸、寡糖、杂环化合物、催化剂、试剂及小分子物质等方面的应用。     

Urea and thiourea based anion receptors in solution and on polymer supports

Herein we report the development of a new series of surface bound anion sensors exploiting the urea or thiourea motif capable of binding anions through hydrogen bonding interactions. The use of high resolution magic angle spinning ¹H NMR allows the direct comparison of the anion binding properties of these receptors in solution versus those tethered to polymer resins. Some intramolecular hydrogen bonding and solvent effects were observed at the solution:surface interface however in general the anion binding properties of the polymer bound urea and thiourea receptors were maintained.     

Preparation and characterization of azlactone functionalized polymer supports and their application as scavengers

A series of cross-linked porous copolymer supports based on N-(p-vinylbenzoyl)-2-methylalanine (VBM), styrene and divinylbenzene was prepared by aqueous suspension copolymerization in the presence of butan-2-ol used as porogen. The cross-linked copolymer beads were characterized by elemental analysis, scanning electron microscopy (SEM), FT-IR and confocal Raman spectrometries. It was observed that the VBM incorporation was effective and homogeneous within the beads. Those VBM functionalized supports were converted into azlactone functionalized supports using acetic anhydride and their scavenging efficiency towards different amines was measured. It appeared that 90% of benzylamine was quenched after 5 h.     

Removal of an olefin metathesis catalyst using 4-nitrophenyl acrylate based polymer supports

A polymer-supported 1,4-butanediolvinyl ether derivative was used for removal of an olefin metathesis catalyst (PCy₃)₂(Cl)₂Ru(3-phenyl-indenylid-1-ene) (M1, PCy₃ = tricyclohexylphosphine) from the reaction solution. Poly(styrene-co-4-nitrophenyl acrylate), cross-linked with either ethylene glycol dimethacrylate or divinylbenzene was prepared via suspension polymerisation and modified chemically to yield a supported acid chloride and subsequently a 1,4-butanediolvinyl ether derivative. A batch reaction of supported vinyl ether with M1 resulted in binding of the catalyst onto the polymer. A high accessibility of up to 43% of reactive sites in the polymer matrix could be achieved.     

Amphiphilic polymer supports for the asymmetric hydrogenation of amino acid precursors in water

This paper describes the synthesis and characterization of a new class of amphiphilic, water-soluble diblock copolymers based on 2oxazoline derivatives with pendent (2S,4S)-4-diphenylphosphino-2-(diphenylphosphinomethyl)pyrrolidine (PPM) units in the hydrophobic block. The synthetic strategy involves the preparation of a diblock copolymer precursor with ester functionalities in the side chain; which were converted into carboxylic acids in a polymer-analogous step and finally reacted with the PPM ligand. The structures of the copolymers were characterized by (1)H and (31)P NMR spectroscopy and GPC measurements. Subsequently, these polymers were successfully utilized as a polymeric support for the asymmetric hydrogenation of 1) (Z)-alpha-acetamido cinnamic acid and 2) methyl (Z)-alpha-acetamido cinnamate in water, showing 90 % substrate conversion at 25 degrees C within 20 minutes at atmospheric H(2) pressure (1 bar) for methyl (Z)-alpha-acetamido cinnamate.