Polymer assisted solution phase

If small or medium libraries for lead optimization are demanded and all synthetic products are to be screened individually, most often parallel synthesis is the method of choice. Parallel syntheses can be conducted in solution, on solid phase, with polymer-assisted solution phase syntheses or with a combination of several of these methods. Preferably, parallel syntheses are automated, either employing integrated synthesis robots or by automation of single steps such as washing, isolation, or identification. The latter concept often allows a more flexible and less expensive automation of parallel synthesis. 

RASP Polymer-assisted solution-phase chemistry... 

An important breakthrough in that respect was the use of soHd-phase organic synthesis (SPOS) where the attachment of the substrate to an insoluble support allowed for easy workup (filtration) and for rapid generation of products via split-mix procedures [1,2]. An important subsequent development consisted of the immobihzation of reagents, scavengers and catalysts. This technique, coined polymer-assisted solution phase chemistry (PASP), allowed solution phase synthesis of compoimds, yet still enjoying the bene-... 

The selective alkylation of a chemically distinct phenohc site on a perfluorinated aromatic has been achieved following a polymer assisted solution phase protection of an alternative o-hydroxybenzoic acid unit as the dioxin-4-one (19) (Scheme 2.45) [66]. A diverse set of 22 different alkyl and benzyl bromides were then attached to the free phenol using cesium fluoride as the base, followed by treatment with Amberlyst 15 and Amberlyst A-21 as the work-up. Subsequent hydrolysis of the dioxin-4-one group with NaOH proceeded smoothly and was quenched... 

Furthermore, polymer-assisted solution-phase syntheses also show several advantages over Merrifield-type syntheses. Fxcept for some industrially employed heterogeneous catalysts the requirement of high loading capacities for the sohd supports is not necessarily of prime importance for immobilized catalysts. Because not every site needs to react, lower loadings are acceptable. The recovered catalyst is often available for immediate reuse. A discussion on immobilized catalysts should also include a brief listing of obstacles associated with their use, particular in comparison to their soluble analogs ... 

POLYMER-ASSISTED SOLUTION-PHASE METHODS FOR CHEMICAL LIBRARY SYNTHESIS... 

This chapter categorizes major approaches to polymer-assisted solution-phase syntheses. It highlights recent reports describing multistep chemical library synthesis using only polymer-assisted purifications, so disproving the assertion that solution-phase syntheses of libraries is limited only to... 

Chemically functionalized polymers have also been used in polymer-assisted solution-phase synthesis to perform reaction-quenching functions. These polymers often are used in operations that substitute for traditional liquid-phase extractions in classical synthesis. 

Polymer-assisted solution-phase synthesis offers strategies for chemical library construction that complement solid-phase methods. Tools now available include chemoselective sequestering resins, bifunctional solution-phase linking reagents, bifunctional chemically tagged reagents, and an... 

Flynn, D. L. Devraj, R. V. Parlow, J. J. Recent Advances in Polymer-Assisted Solution-Phase Chemical Library Synthesis and Purification, Curr. Opin. Drug Disc. Dev. 1998, 7, 41. 

EDC FDPP Fmoc HOBt LiHMDS MAMP MCPBA MeOPEG NCA NMP PAL PASP PBP PEG SASRIN TEA TFA TMAD N-Ethyl-N - [ 3 - (dimethy lamino)propy 1] -c arbodiimide hydrochloride Pentafluoro phenyldiphenyl phosphate 9 -Fluoreny lme thoxy c arbony 1 Hydroxybenzotriazol Lithium hexamethyldisilazane Merrifield, alpha methoxy phenyl resin w-Chloroperbenzoic acid Methoxy polyethylene glycol /V-Carboxv a-aminoacid anhydride /V - M e t h v 1 pyrrol i do n e Peptide amide linker Polymer assisted solution phase Penicillin-binding proteins Polyethylene glycol Super acid sensitive resin Triethylamine Trifluoroacetic acid Tetramethylamine azodicarboxylate. 

Scheme 5 Application of polymer-assisted solution phase (PASP) technique in Staudinger...

One of the major innovations in combinatorial and medicinal chemistry in recent years aiming at efficient diversity-oriented synthesis has been the implementation of polymer reagents in polymer-assisted solution phase (PASP) synthesis. This contribution will present—following an introduction to the field—a concept of advanced polymer reagents based on reactive intermediates and active reactants that should extend the scope PASP synthesis significantly. Experimental procedures describing preparation and use of the novel polymer reagents are included. 

Polymer-Assisted Solution Phase (PASP) Synthesis... 

Fig. 1. Polymer-assisted solution phase (PASP) synthesis combines the merits of solution-phase chemistry with the advantages of facilitated phase separation by using polymer reagents (a) or scavenger resins (b).

Thus, isolation of oxoammonium salts on insoluble, cross-linked polymer supports was investigated along with their implementation in polymer-assisted solution-phase synthesis.23 These isolated oxoammonium salts could be employed in a water-free system to generate highly reactive oxidation agents without the overoxidation problems normally seen in the presence of water. 

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