Wang Resin Research Articles

Photoactive hybrid materials of lanthanide (Eu3+, Tb3+, Sm3+) beta-diketonates and polymer resin through ionic liquid bridge.

A special multifunctional ionic liquid compound (1-methyl-3-(2-(thiocarboxyoxy)-ethyl)-2H-imidazole-1,3-diium bromide (SHIL)) is used as the chemical bridge to link lanthanide beta-diketonates and polymer resin, which are designated as Ln(L)4-SHIL-WR/MR (Ln = Eu, Tb, Sm; L = thenoyltrifluoroacetonate (TTA), acetylacetonate (AA), dibenzoylmethane (DBM); WR = Wang resin, MR = Merrifield resin). Among SHIL and polymer resin are assembled to form covalently bonded system through condensation reaction. Then tetrakis lanthanide beta-diketonates are linked to SHIL through ion-exchange reaction. Physical characterization and especially the photoluminescent performance of the multicomponent hybrids are studied. The hybrid materials possess good stability and excellent luminescent property. The results provide useful path to obtain luminescent hybrids for further practical application.

Solid-phase Synthesis of Bacterial Cell Wall Peptidoglycan Fragments

Abstract Bacterial cell wall peptidoglycan (PGN) is a major innate immunostimulant of bacteria and an important antibiotic target. Chemically prepared PGN fragments are indispensable for the investigation of their function. In this research, the PGN fragments containing acid- and base-labile functional groups were practically synthesized by utilizing a newly developed solid-phase method employing the JandaJel™ Wang resin.

Solid-phase synthesis of anagrelide sulfonyl analogues.

Simple solid-phase synthesis of 3,10-dihydro-2H-benzo[e]imidazo[1,2-b][1,2,4]thiadiazin-2-one 5,5-dioxides is described, with Fmoc-α-amino acids and 2-nitrobenzenesulfonyl chlorides (2-NosCls) being the key building blocks. Fmoc-α-amino acids were immobilized on Wang resin and transformed to the corresponding 2-nitrobenzenesulfonamides in two steps. After reduction of the nitro group, Fmoc-thioureas were synthesized followed by cyclization of the 1,2,4-benzothiadiazine-1,1-dioxide scaffold with diisopropylcarbodiimide (DIC). Cleavage of the Fmoc protecting group followed by spontaneous cyclative cleavage gave the target products in excellent crude purity.

Solid-Phase Synthesis of Pyrrole-Imidazole Polyamides by Resin

Over the past years, synthesis of pyrrole-imidazole (Py-Im) polyamides has been achieved by solution-phase and solid-phase methods. Comparing with solution-phase synthesis, the solid-phase synthesis has showed great superiority in various aspects. The solid-phase synthesis is a rapid, effective, energy-saving and environment-friendly method, which has been widely used in the synthesis of pyrrole-imidazole polyamides. Many complicated polyamides can be obtained quickly and effectively through this method. By far, the application of the solid-phase synthesis for Py-Im polyamides has made rapid development. Resin as the main carrier, a key substance in solid phase synthesis, consists of two parts: polymer (macromolecular resin) and linking chain (linker). To date, there are many kinds of resins applied in the solid phase synthesis, such as PAM resin, Wang resin, Oxime resin and Clear resin, and so on. In this article, we will focus on the elaboration about the basic principle and application of the four kinds of resins mentioned above in solid-phase synthesis of polyamides. This provides an important reference for development of polyamides.

Solid-Phase Synthesis of 5-Noranagrelide Derivatives

Solid-phase synthesis of 1H-benzo[d]imidazo[1,2-a]imidazol-2(3H)-one derivatives employing Fmoc-α-amino acids and nitroaryl fluorides as key building blocks has been developed. The Fmoc-α-amino acids immobilized on Wang resin, equipped with a piperazine carbamate linker, were transformed to o-nitroanilines in two steps. After reduction of the nitro group, the corresponding o-phenylenediamines gave the 2-aminobenzimidazole scaffold by reaction either with cyanogen bromide or with Fmoc-NCS. Cleavage from the polymer support and further cyclization afforded the target compounds. The developed methodology represents a versatile and simple approach for the preparation of various corresponding 1H-benzo[d]imidazo[1,2-a]imidazol-2(3H)-ones from a large number of commercially available building blocks.

Synthesis of Molecularly Encoded Oligomers Using a Chemoselective “AB + CD” Iterative Approach

A library of eight sequence-defined model oligomers, whose sequence is based on a (0,1) binary code, is prepared through chemoselective repeating cycles of amidification and copper-assisted alkyne-azide cycloaddition reactions from a non-modified Wang resin. This library is constructed from two AB (A = acid, B = alkyne) building blocks, i.e., 4-pentynoic acid and 2-methyl-4-pentynoic acid acting, respectively, as non-coding (0) and coding (1) monomer, and 1-amino-11-azido-3,6,9-trioxaundecane as complementary CD (C = amine, D = azide) spacer building block. In particular, encoded triads are synthesized by consecutive covalent attachment of five building blocks (i.e., three coding/non-coding monomers and two spacers). In this communication, optimal protocols for the synthesis of the targeted oligomers are reported along with their full characterization by (1) H NMR, MALDI-TOF mass spectrometry, and size-exclusion chromatography. It is found that all possible encoded triads (i.e., eight possibilities) could be synthesized using this approach. Indeed, monodisperse sequence-defined oligomers are prepared and characterized in all cases.

An optimized Fmoc synthesis of human defensin 5

Human α-defensin 5 (DEF5), expressed by the Paneth cells of human small intestine, plays an important role in host defense against microbial infections. DEF5, a 32-residue peptide adopting a three-stranded β-sheet fold stabilized by three internal disulfide bonds, is not efficiently produced by recombinant expression techniques and is, therefore, an interesting goal for chemical synthesis. While DEF5 production by Boc-based solid-phase synthesis has been described, to date no synthetic account by the more convenient Fmoc method has been published. Herein, we report an optimized solid-phase synthesis of DEF5 using the Fmoc strategy. Starting from a rather problematic initial synthesis using standard Wang resin and coupling protocols, the sequence elongation process has been monitored by mini-cleavage and MS analysis at strategic points, to identify problematic spots and act accordingly. For expediency, some of the optimization rounds have been run on defensin 5 amide. Main modifications have included the ChemMatrix(®) resin, known to decrease chain aggregation, and the use of pseudoproline dipeptide units at selected positions. Combination of some of these improvements results in a significantly purer product, to the extent that it can undergo in situ anaerobic oxidative folding to the native form without the need of an intermediate purification step. A typical synthesis run yielded about 15 mg of >95 % pure material. This approach should facilitate production of DEF5 and of selected analogs for structure-activity studies and other applications.

ChemInform Abstract: The Synthesis of Enantiomers of 6‐tert‐Butyl‐6‐methylmorpholine‐2,5‐dione Using Wang Resin Supported Mukaiyama Reagent.

ChemInform Abstract: The Synthesis of Enantiomers of 6‐tert‐Butyl‐6‐methylmorpholine‐2,5‐dione Using Wang Resin Supported Mukaiyama Reagent.

Merrifield and Wang Resins Functionalized with Bidentate Amines: Useful Materials to Support Reducing Complexes and as Alkali Metal Sensors

AbstractEight chelating resins were synthesized in high yields by supporting 2‐aminomethylpyridine, 2,2′‐dipyridylamine, 1,2‐phenylenediamine and 1,2‐ethylenediamine on Merrifield and Wang resins, respectively. These resins were used both as support of reducing complexes and as alkali metal sensors. 16 stable and easy to prepare reducing complexes, derived from the chelating resins and LiBH4 and NaBH4, were prepared in good yields. These complexes showed chemoselectivity to reduce aldehydes in a low molar ratio and short time reactions. The fluorescence‐sensing behavior of the chelating resins for alkali metal was studied. The fluorescence response of the materials where 1, 2‐phenylenediamine is supported on Merrifield and Wang resins indicate that they behave as sensors for Li+and K+, respectively.

ChemInform Abstract: The Dimethylsulfoxonium Methylide as Unique Reagent for the Simultaneous Deprotection of Amino and Carboxyl Function of N‐Fmoc‐α‐Amino Acid and N‐Fmoc‐Peptide Esters.

AbstractThis method can also be used in solid‐phase peptide synthesis to simultaneously deprotect the amino function and cleave the peptide from the Wang resin.

Polymer‐Supported Stereoselective Synthesis of (1S,5S)‐6‐Oxa‐3,8‐diazabicyclo[3.2.1]octanes

AbstractWe describe a polymer‐supported stereoselective synthesis of the (1S,5S)‐6‐oxa‐3,8‐diazabicyclo[3.2.1]octane‐bridged scaffold by tandem iminium ion cyclization/nucleophilic addition reactions. A series of resin‐bound acyclic intermediates bearing different substituents were prepared, and the scope and limitations of the chemical route leading to the bridged scaffold were evaluated. The Thr‐derived bridged scaffold was found to be substantially more stable in acid than the Ser‐derived scaffold, which was partially transformed into dihydropyrazinones. Substitution at the iminium‐forming nitrogen was critical for acid stability, and the N‐arylsulfonamides with electron‐withdrawing groups yielded the highest purity of the crude products prepared by acid‐mediated cleavage. The acid‐labile target compounds were synthesized by nucleophile‐mediated cleavage from the esterified Wang resin and cyclization in formic acid.

The Synthesis of Enantiomers of 6-tert-Butyl-6-methylmorpholine-2,5- dione Using Wang Resin Supported Mukaiyama Reagent

The synthesis of enantiomers of 6-tert-butyl-6-methylmorpholine-2,5-dione (3) using Wang resin supported 2- chloro- or 2-bromo- pyridinium triflate is described. The applied methodology could be considered as an interesting alternative to “classical” one and enables the synthesis of 6-tert-butyl-6-methylmorpholine-2,5-dione with higher yields and the isolation of product (3) is significantly easier. Keywords: Wang resin supported Mukaiyama reagent, enantiomers of 6-tert-butyl-6-methylmorpholine-2, 5-dione, glycine equivalent.

Fast and effective reduction of nitroarenes by sodium dithionite under PTC conditions: application in solid-phase synthesis

Herein, conditions for the fast and effective reduction of aromatic nitro groups bound to hydrophobic polystyrene-based Wang and Ring resins utilizing sodium dithionite in dichloromethane–water under PTC conditions are reported. Tetrabutylammonium hydrogen sulfate (TBAHS) was found to be an effective phase-transfer catalyst for this reaction. This method allows for the reduction of nitro groups to amino groups under mild conditions with complete conversion and is tolerant of other functional groups. This method is a superior alternative to tin(II) chloride-based reduction, which is known for its shortcomings.

A Facile Solid‐Phase Synthesis of (+)‐(S)‐Clopidogrel

AbstractEnantiomerically pure (+)‐(S)‐clopidogrel was prepared by solid‐phase synthesis using the commercially available Wang resin. This method offers mild reaction conditions and provides the (+)‐(S)‐clopidogrel in overall 52% yield over six steps and with optical purity of 98.0% ee.

Cool-white light emitting hybrid materials of a resin–mesoporous silica composite matrix encapsulating europium polyoxometalates through an ionic liquid linker

Benzoate (4-hydroxybenzoate, 4-mercaptobenzoate and 4-aminobenzoate) functionalized polymer resin (Merrifield resin (MR) or Wang resin (WR)) and mesoporous silica SBA-15 are connected to assemble photofunctional hybrids by bridging lanthanide ions (Gd3+, Eu3+) through coordination bonds. The organically functionalized mesoporous SBA-15 are synthesized by co-condensation of tetraethoxysilane (TEOS) and modified by organic coupling agent 3-methacryloxypropyltrimethoxy-silane (denoted as MPTMS) in the presence of Pluronic P123 surfactant as a template. Europium polyoxometalates (Na9EuW10O36·32H2O, abbreviated as Na9EuW10) are encapsulated into the composite host through an ionic liquid (1-methyl-3-(trimethoxysilylpropyl) imidazolium) as a double linker, which is fixed on the surface of mesoporous SBA-15. The detailed physical characterization of these photofunctional hybrids are characterized by Fourier Transform Infrared (FTIR), X-ray diffraction (XRD), Thermo-gravimetric Analysis (TGA), Transmission Electron Micrographs (TEM), N2 absorption and desorption and luminescent performance. It is worth pointing out that some hybrids possess high luminescent output (quantum yields) and long decay time (reaching the millisecond scale) and cool-white light (from CIE diagrams). The research provides a strategy to assemble multi-component hybrids to realize the cool-white integration.

Wang Linker Free of Side Reactions

A new resin for the solid-phase synthesis of peptide acids was developed. It was based on a linker with two unique features: methoxy groups as the only activating groups of the phenyl ring and a copper(I)-catalyzed Click chemistry reaction to anchor it to the solid support. The efficiency of this new resin in solid phase peptide synthesis was compared with that of Wang resin.

Solid Phase Asymmetric Benzylation Using 5,5-Dimethyl-2-Phenylamino-2-Oxazoline Chiral Auxiliary

Solid phase synthesis has emerged as a versatile and powerful method in modern organic synthesis. 1 However, the application of solid-supported chiral auxiliaries is still relatively underdeveloped. Such solid-supported chiral auxiliaries offer some advantages as compared to their application in the solution phase, including a simple filtration procedure for the isolation of the desired compounds or the recovery of the expensive chiral auxiliaries, and their possible extension to a continuous flow system. 2 In addition, the microenvironment of the polymeric backbone could lead to an improvement in the stereoselectivity for a given transformation. 2a,4a Recently, we have investigated 2-phenylamino2-oxazolines as effective chiral auxiliaries for asymmetric alkylation, which provided some beneficial effects for the removal problem as well as stereoselectivity. 3 As a part of our interest in solid-supported chiral auxiliaries, 4 we herein wish to introduce 5,5-dimethyl-2-phenylamino-2-oxazoline chiral auxiliary in solid phase as a good leaving group in the final cleavage step. Asymmetric benzylation as a model alkylation reaction using this chiral auxiliary with different cleavage conditions for the parallel synthesis of several kinds of chiral products will be discussed. First, 5,5-dimethyl-2-phenylamino-2-oxazoline chiral auxiliary 5 was prepared from commercially available methyl ester hydrochloride 1 in 4 steps (Scheme 1). The 1,2-aminoalcohol 2 was synthesized according to the previous procedure by treatment with the methylmagnesium bromide. 3b The reaction of aminoalcohol 2 with phenyl isothiocyanate afforded the thiourea 3 in excellent yield, and the cyclization of the thiourea to the 2-phenylamino-2-oxazolines by a onepot reaction using p-toluenesulfonyl chloride and sodium hydroxide gave the chiral auxiliary 4 in 91% yield. 3 Finally, the desired chiral auxiliary 5 was formed after removing the O-protecting benzyl group of 4. With the free hydroxy group, chiral auxiliary 5 was conveniently linked to resin to carry out the asymmetric synthesis in the solid phase. Next, the solid-supported 5,5-dimethyl-2-phenylamino-2oxazoline chiral auxiliary 6 was formed by the reaction of compound 5 and Wang resin under Mitsunobu conditions using diisopropyl azodicarboxylate (DIAD) and triphenyl phosphine (Ph3P). Acylation in the solid phase was carried out by deprotonation of resin 6 with excess potassium tertbutoxide (10 equiv), followed by treatment with excess propionyl chloride (10 equiv) to afford resin 7 (Scheme 2). The monitoring of the reaction progress in the solid phase may be achievable by using the conventional TLC of compound 8 after the cleavage of the acylated resin 7 with trifluoroacetic acid (TFA). 4 However, we failed to monitor the acylated compound 8. The treatment of resin 7 with TFA for 5 min at room temperature provided the mixture of

The Heck reaction of polymer-supported allylamine with aryl iodides

The Heck reaction of Wang resin-bound allylamine with aryl iodides produces various, substituted cinnamylamines. The catalyst and additive system consisting of palladium(II) acetate, n-Bu4NOAc and potassium chloride, in addition to potassium carbonate in N,N-dimethylformamide, accomplishes a regioselective γ-arylation. By utilising the easily formed and stable carbamate linker on Wang resin, the incompatibility of free amines with the palladium catalyst is avoided. The cinnamylamine products are cleaved from the resin with trifluoroacetic acid under mild conditions and are converted into chromatographically separable acetamides. Our solid-phase method offers a new alternative for the synthesis of cinnamylamine derivatives, as biologically interesting compounds and useful synthetic intermediates.

Enantioselective Solid‐Phase Peptide Synthesis Using Traceless Chiral Coupling Reagents and Racemic Amino Acids

AbstractThe enantioselective condensing reagent 4,6‐dimethoxy‐1,3,5‐triazine (DMT)/strychnine/BF$\rm{{_{4}^{-}}}$ was obtained by treatment of 2‐chloro‐4,6‐dimethoxy‐1,3,5‐triazine (CDMT) with strychnine tetrafluoroborate. The reagent was useful under typical conditions of solid‐phase peptide synthesis (SPPS) with enantiomerically homogeneous substrates. By SPPS, desired dipeptides were obtained in 84–94% yield using 4 equiv. of racemic Fmoc‐Ala, Fmoc‐Phe, and/or Fmoc‐Tyr for 1 equiv. of Wang resin loaded with Gly, Ala, Leu, Phe, Glu(tBu), and/or Pro, respectively. For all three Fmoc‐protected amino acids, the configuration of the enantiomer preferred under SPPS conditions was independent of the structure of the acylated component and identical to that established in condensations proceeding in solution. In all cases, the enantiomer ratios L/D (er) were in a similar range, and varied from 9 : 92 to 2 : 98 for alanine, and from 90 : 10 to 100 : 0 for aromatic amino acids. The synthesis of Ac‐L‐Lys(Ac)‐D‐Ala‐D‐Ala‐OH from racemic Fmoc‐Ala gave an L/D ratio of 10 : 90 for the esterification of Wang resin, and 0 : 100 for the formation of peptide bonds.

ChemInform Abstract: Preparation of Poly(ethylene Glycol) Acrylate Grafted Polystyrene Resin for Solid‐Phase Peptide Synthesis

AbstractReview: 41 refs.