Polymer-supported building blocks

Varma and Kappe have developed a method that enables the rapid and parallel synthesis of DHPM 58 (Scheme 8.22) but does not rely on polymer-supported building blocks and therefore does not require the development of solid-phase linkingcleaving chemistry. They showed that polyphosphate ester (PPE) serves as an excel-... 

In this chapter we describe the basic principles involved in the controlled production and modification of two-dimensional protein crystals. These are synthesized in nature as the outermost cell surface layer (S-layer) of prokaryotic organisms and have been successfully applied as basic building blocks in a biomolecular construction kit. Most importantly, the constituent subunits of the S-layer lattices have the capability to recrystallize into iso-porous closed monolayers in suspension, at liquid-surface interfaces, on lipid films, on liposomes, and on solid supports (e.g., silicon wafers, metals, and polymers). The self-assembled monomolecular lattices have been utilized for the immobilization of functional biomolecules in an ordered fashion and for their controlled confinement in defined areas of nanometer dimension. Thus, S-layers fulfill key requirements for the development of new supramolecular materials and enable the design of a broad spectrum of nanoscale devices, as required in molecular nanotechnology, nanobiotechnology, and biomimetics [1-3]. 

As a suitable model reaction, the coupling of various substituted carboxylic acids to polymer resins has been investigated by Stadler and Kappe (Scheme 7.8) [28]. The resulting polymer-bound esters served as useful building blocks in a variety of further solid-phase transformations. In a preliminary experiment, benzoic acid was attached to Merrifield resin under microwave conditions within 5 min (Scheme 7.8 a). This functionalization was additionally used to determine the effect of micro-wave irradiation on the cleavage of substrates from polymer supports (see Section 7.1.10). The benzoic acid was quantitatively coupled within 5 min via its cesium salt utilizing standard glassware under atmospheric reflux conditions at 200 °C. 

Additionally, the authors chose 3-chloropropionyl chloride as the immobilized building block in order to carry out a ring-expansion approach, which led to the generation of a 14-member library of thioxotetrahydropyrimidinones [85, 86], The initially prepared polymer-bound chloropropionyl ester was efficiently transformed into the corresponding diamines by transamination utilizing several primary amines. These diamine intermediates could also be obtained by treatment of the pure polymeric support with acryloyl chloride and subsequent addition of the appropriate amines (Scheme 7.74). 

Microwave-mediated transesterification of commercially available neat poly(styr-ene-co-allyl alcohol) with ethyl 3-oxobutanoate, ethyl 3-phenyl-3-oxopropanoate, and diethyl malonate provided the desired polymer-supported /i-dicarbonyl compounds (Scheme 12.18) [65]. Multigram quantities of these interesting building blocks for heterocycle synthesis were obtained simply by exposing the neat mixture of reagents to microwave irradiation in a domestic microwave oven for 10 min. 

These results demonstrate that O-glycosyl trichloroacetimidate-based oligosaccharide synthesis on solid support may eventually become a valuable alternative to solution-phase synthesis because useful experience is available for the selection of the polymer support and choice of the linker system and the glycosyl donor. Further standardization of the building blocks and the protective group pattern will finally provide the yields and the anomeric control in order to successfully plan automated syntheses of oligosaccharides also in a combinatorial manner. 

Addition of 81-SH to 80-SS-81 led to formation of the homodisulfide compounds and an equilibrium, with an exchange constant of 1.8, was established. The presence of the templating (D)Pro(L)Val(D)Val tri-peptide in this mixture, shifted the equilibrium dramatically and the formation of the homodisulfide 80-SS-80 was amplified with a Keq=32. Since the templating tri-peptide was supported on polymer beads, the isolation of receptor 80-SS-80 (in 97% purity) was achieved easily by extraction of the beads. The formation of multiple hydrogen bonds between the template and the components of the DCL, led to the isolation of the best possible receptor available from the building blocks present in the equilibrated mixture. 

Scheme 81. Examinations of other possibilities to bind the chlorocyclopropylideneacetate building block onto a polymer support [11b]...

Methacrylate monoliths have been fabricated by free radical polymerization of a number of different methacrylate monomers and cross-linkers [107,141-163], whose combination allowed the creation of monolithic columns with different chemical properties (RP [149-154], HIC [158], and HILIC [163]) and functionalities (lEX [141-153,161,162], IMAC [143], and bioreactors [159,160]). Unlike the fabrication of styrene monoliths, the copolymerization of methacrylate building blocks can be accomplished by thermal [141-148], photochemical [149-151,155,156], as well as chemical [154] initiation. In addition to HPLC, monolithic methacrylate supports have been subjected to numerous CEC applications [146-148,151]. Acrylate monoliths have been prepared by free radical polymerization of various acrylate monomers and cross-linkers [164-172]. Comparable to monolithic methacrylate supports, chemical [170], photochemical [164,169], as well as thermal [165-168,171,172] initiation techniques have been employed for fabrication. The application of acrylate polymer columns, however, is more focused on CEC than HPLC. 

Hydroxymethyl furfural. 2,5-diformylfuran (DFF) is a furan derivative that has many uses, including use as a polymer building block. By utilizing a platinum catalyst supported on carbon, and running the reaction in water at high temperatures, DFF is produced as the major product in neutral solution. If low temperatures and high pH are employed, 2,5-furandicarboxylic acid results. 

We have often mentioned polyethylene glycols (PEGs) related to their roles as building blocks for polyurethanes. These polymers are also well known for their protein compatibility. Adsorption was shown to be inversely related to the length of the PEG molecule. This work supported the work of Jeon discussed in Chapter 2. 

As a suitable model reaction, the coupling of various substituted carboxylic acids to polymer supports has been investigated (Scheme 7.7)27. The resulting polymer-bound esters served as useful building blocks in a variety of further solid-phase transformations. In a preliminary experiment, benzoic acid was attached to Merrifield resin under... 

The reactivity of a building block with different polymer-supported substrates can be evaluated in one reaction vessel. 

Another application of hyperbranched polymers as supports for catalysts is their use as backbones for the covalent attachment of organometallic fragments. NCN-pincer complexes (NCN-pincer = 2,6-bis[(dimethylamino)-methyl] phenyl anion) are attractive building blocks for catalytic reactions [20,21], Covalent introduction of the transition-metal complexes can also be of interest for visualization and imaging of dendritic polymers by transmission electron microscopy (TEM). 

Polymer structures derived from this building block were supported by similar spectral characterization as that described for polymers obtained from the acyl chloride 6. Condensation of bisacetate 7 below 170°C was found to be slow whereas at 250°C, the rate was substantially increased. Products (possessing M > 1,000,000 amu) were much less sensitive to starting material (i.e., 7) purity than those synthesized employing TMS-monomer 6. 

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