Polymer-supported Synthesis Research Articles

Electrolysis as an Efficient Key Step in the Homogeneous Polymer-Supported Synthesis of N-Substituted Pyrroles

[reaction: see text]. An efficient and general route to the soluble polymer-assisted synthesis of a set of 14 different N-substituted pyrroles using dendritic polyglycerol as a high-loading support is presented. The transformation of furan to the key intermediate 2,5-dialkoxytetrahydrofuran was performed by electrochemical oxidation followed by catalytic hydrogenation with Pt/C in high yield. Both reactions required heterogeneous reagents which can be conveniently used with polyglycerol as a soluble support.

Sulfur- and selenium-based linkers in polymer-supported organic synthesis

The use of sulfur- and selenium-based linkers in polymer-supported organic synthesis (PSOS) is reviewed. The literature describing the application of sulfur-based linkers in the PSOS of small molecules and combinatorial library preparation from 2000 to the present is summarized. The development and use of selenium-based linkers in PSOS, highlighting the work of the Nicolaou and Huang groups, is also presented.

Polymer-Supported Synthesis of Mono-substituted Porphyrins

Abstract Anchoring of substituted benzaldehydes to soluble and insoluble polymers allows for the synthesis of mono-substituted tetraarylporphyrins without the production of di-, tri-, and tetra-substituted porphyrin side products. The exclusion of the aforementioned side products during the synthesis of mono-substituted tetraarylporphyrin acids greatly reduced the complexity during purification of the product.

Combinatorial Parallel Synthesis of Biologically Active Libraries on Soluble Polymer Supports

AbstractFor Abstract see ChemInform Abstract in Full Text.

Barbier allylation–Prins reaction of PEG-bound aldehydes—soluble polymer-supported synthesis of 2,4,6-trisubstituted tetrahydropyrans

PEG-bound aldehydes undergo zinc-mediated Barbier allylation to form homoallylic alcohols, which on further reaction with various aldehydes in the presence of BF 3·Et 2O through a Prins cyclization afford 4-hydroxytetrahydropyrans and 4-fluorotetrahydropyrans.

Polymer-supported synthesis of mono-substituted porphyrins

Anchoring of substituted benzaldehydes to soluble and insoluble polymers allows for the synthesis of mono-substituted tetraarylporphyrins without the production of di-, tri-, and tetra-substituted porphyrin side products. The exclusion of the aforementioned side products during the synthesis of mono-substituted tetraarylporphyrin acids greatly reduced the complexity during purification of the product.

Polymer-Supported Synthesis of Bicyclic γ-Lactams

Polymer-Supported Synthesis of Bicyclic γ-Lactams

Efficient synthesis of the nonamannoside residue of high mannose glycoproteins

An efficient synthesis of the nonamannoside residue 1 of high mannose glycoproteins was achieved using an oligomer-supported solution synthesis with low-molecular-weight polyethylene glycol as the anchor. The synthesis required only five coupling steps from only two monosaccharide building blocks with an overall yield of 12%.Key words: nonamannoside, oligosaccharide synthesis, soluble polymer support synthesis, glycoproteins.

Soluble Polymer-Supported Synthesis of 4-Methyl Coumarin on Modified Poly(ethylene glycol)s

A simple liquid phase synthetic method for the preparation of 4-methyl coumarin on modified poly(ethylene glycol)s by using the von Pechmann reaction is described.

PolyHIPE Supports in Batch and Flow-Through Suzuki Cross-Coupling Reactions

As part of ongoing research efforts to discover alternative support materials to polymer beads for use in polymer-supported synthesis, particularly under flow-through conditions, this work involves the synthesis of PolyHIPE (High Internal Phase Emulsion) polymer monoliths. PolyHIPEs containing high loadings of chloromethyl groups were efficiently prepared by the direct copolymerization of 4-vinylbenzyl chloride and divinylbenzene monomers. The ‘Merrifield' PolyHIPE proved to be an excellent support for batch and flow-through Suzuki cross-coupling reactions. A remarkably high yield of pure biaryl product was obtained using the PolyHIPE support in cubic form and utilizing an electron-rich boronic acid. In comparison to polymer beads, this material was found to be a much more efficient support in both batch and continuous flow modes. PolyHIPE converted a greater amount of chloromethyl groups into biaryl product under identical reaction conditions. It is suggested that the absence of channelling with PolyHIPE monoliths gives better performance under flow-through conditions than permanently porous beads.

The synthesis of diaminopimelic acid containing peptidoglycan fragments using metathesis cross coupling

Properly protected diaminopimelic acid (DAP), a component of peptidoglycan of Gram-negative bacteria, was prepared by a metathesis cross coupling between properly protected allyl and vinyl glycine derivatives using Grubb’s second-generation catalyst followed by reduction of the double bond of the resulting compound. The DAP derivatives were used in the solution- and polymer-supported synthesis of biological active peptides.

Resin-Supported Sulfonic Acid

There has been a plethora of polymer-supported syntheses since Merrifield began peptide synthesis on the solid phase. [1] Solid-phase organic synthesis (SPOS) has become a very efficient method for production of combinatorial libraries. [2] Resinsulfonic acid is one of the important functional polymer, which is already developed in organic synthesis. [3] Resinsulfonic acids are particularly useful for the removal of basic compounds such as primary, secondary and tertiary amines. On the other hand, they are used as a separator and/or electrolyte in membrane-separated chlor-alkali cells and other electrochemical processes, solid polymer electrolyte fuel cells and batteries. [3a] The use of resinsulfonic acids in organic synthesis was serendipitous. Generally, they are used as Brønsted acid in organic synthesis. Compared to conventional Brønsted acids, they have advantages of recyclability, operational simplicity and they can often be used in just ­catalytic amounts. Of late, resinsulfonic acids such as ­sulfonated polystyrenes (Dowex-50, Amberlite IR-112, ­Permutit-Q) and Nafion-H are commercially available.

Soluble Polymer-supported Synthesis of trans β-Lactams with High Diastereoselectivity

Abstract A general method for the liquid-phase synthesis of trans β-lactams with high diastereoselectivity is described. The mechanism can be explained by a chair-like transition state involving the imine and the (Z)-enolate.

Soluble polymer‐supported synthesis of pyrazoles via 1,3‐dipolar cycloaddition strategy

AbstractRapid parallel liquid‐phase synthesis of pyrazoles has first been developed. The 1,3‐dipolar cycloaddition between nitrilimines generated in situ and soluble polymer‐supported alkynyl or alkenyl dipolarophiles in parallel one‐pot fashion gave the corresponding PEG‐supported regioisomeric pyrazoles or regiospecific pyrazolines. The latter was assuredly oxidated by DDQ to PEG‐supported regiospecific pyrazoles. Cleavage from the support under mild conditions afforded pyrazoles in good yields and high purity.

Solid‐Phase Synthesis of Oligo(triacetylene)s and Oligo(phenylenetriacetylene)s Employing Sonogashira and CadiotChodkiewicz‐Type Cross‐Coupling Reactions

AbstractWe describe the first polymer‐supported synthesis of poly(triacetylene)‐derived monodisperse oligomers, utilizing Pd0‐catalyzed Sonogashira and CadiotChodkiewicz‐type cross‐couplings as the key steps in the construction of the acetylenic scaffolds. For our investigations, Merrifield resin functionalized with a 1‐(4‐iodoaryl)triazene linker was chosen as the polymeric support (R2; Figure and Scheme 3). The linker selection was made based on the results of several model studies in the liquid phase (Schemes 1 and 2). For the solid‐support synthesis of the oligo(phenylene triacetylene)s 7b–7d, a set of only three reactions was required: i) Pd0‐catalyzed Sonogashira cross‐coupling, ii) Me3Sialkyne deprotection by protodesilylation, and iii) cleavage of the linker with liberation of the generated oligomers (Scheme 5). The longest‐wavelength absorption maxima of the oligo(phenylene triacetylene)s 7a–7d shift bathochromically with increasing oligomeric length, from λmax 337 nm (monomer 7a) to 384 nm (tetramer 7d; Table 2). Based on the electronic absorption data, the effective conjugation length (ECL) of the oligo(phenylene triacetylene)s is estimated to involve at least four monomer units and 40 C‐atoms. π‐Electron conjugation in these oligomers is less efficient than in the known oligo(triacetylene)s 14a–14d (Table 2) due to poor transmittance of π‐electron delocalization by the phenyl rings inserted into the oligomeric backbone. Similar conclusions were drawn from the electrochemical properties of the two oligomeric series as determined by cyclic (CV) and rotating‐disk voltammetry (RDV; Table 3). In sharp contrast to 14b–14d, the oligo(phenylene triacetylene)s 7b–7d are strongly fluorescent, with the highest quantum yield ΦF=0.69 measured for trimer 7c (Table 2). Whereas the Sonogashira cross‐coupling on solid support proceeded smoothly, optimal conditions for alkynealkyne cross‐coupling reactions employing Pd0‐catalyzed CadiotChodkiewicz conditions still remain to be developed, despite extensive experimentation (Scheme 7 and Table 1).

Synthesis of diverse macrocyclic peptidomimetics utilizing ring-closing metathesis and solid-phase synthesis.

The synthesis of a range of highly functionalized peptidomimetic macrocycles has been accomplished using ring-closing metathesis and enyne tandem cross-metathesis-ring-closing metathesis reactions. This approach gives access to rigidified macrocycles modeled on the structures of cyclic peptides and designed to be biologically stable. The potential for peripheral functionalization of these templates has been demonstrated using Diels-Alder reactions, palladium(0) coupling reactions, and amide formation both in the solution phase and using polymer-supported syntheses.

Soluble polymer-supported synthesis of thioxotetrapyrimidinone by focused microwave irradiation.

Soluble polymer-supported synthesis of thioxotetrapyrimidinone by focused microwave irradiation.

Soluble Polymer-Supported Synthesis of α-Amino Acid Derivatives

A practical and efficient synthesis of N-substituted α-amino acid derivatives on soluble polymer support is described.

Microwave-Assisted Polymer-Supported Combinatorial Synthesis

Lead identification and optimization is always a challenge to the medicinal chemists in drug discovery. Numbers of simple to complex and smaller to bigger organic compounds are prepared to meet the screening purpose of biological targets. Conventional solution phase synthetic methodologies are lacking the speed to run along with the need of medicinally interesting compounds due to their long reaction time, tedious work-up and purification problems. Alternatively opted polymer-supported synthesis of combinatorial libraries has been emerged as a promising tool in generating large numbers of structurally diverse molecules in a manner rapid and parallel. Microwave-assisted solid/liquid phase combinatorial synthetic techniques have been proved efficient in reducing the reaction time from days & hours to minutes & seconds and more promisingly to produce improved yields with high purities. This review briefs about the theory behind microwave chemical technology and glimpses of recent advancements in its application on polymer supported combinatorial synthesis.

Peptide Heterocycle Conjugates: A Diverted Edman Degradation Protocol for the Synthesis of N-Terminal 2-Iminohydantoins.

For Abstract see ChemInform Abstract in Full Text.