Solution phase chemistry, polymer-assiste

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-... 

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).

Since the experimental conditions for the traditional Biginelli reaction are quite straightforward, small libraries of DHPMs are readily accessible by parallel synthesis. Along these lines the generation of a 140-member single compound DHPM library by combination of 25 aldehydes, 6 ureas/thioureas, and 7 acetoacetates or acetoamides under standard reaction conditions has been reported [123, 124]. More rapid approaches make use of microwave-enhanced solution-phase protocols [88, 89, 125]. Apart from these conventional solution-phase methods, it is also possible to employ polymer-supported reagents to aid in the purification and workup protocol. Polymer-assisted solution-phase chemistry using polymer-supported... 

In this chapter we discuss the new speeding-up techniques, optimized during the last decade, such as solid-phase extraction, polymer-assisted solution-phase synthesis, microwave-assisted organic synthesis, and flow chemistry. The improvements obtained with these techniques are not limited to a subset of chemical reactions (e.g., the reported examples), but they are fully applicable to the entire set of chemistry involved in the synthetic drug discovery process. 

Polymer-Assisted Solution-Phase Chemistry (PASP) 121... 

Under certain condition, however, reactions are still preferably conducted in solution. This is the case e.g., for heterogeneous reactions and for conversions, which deliver complex product mixtures. In the latter case, further conversion of this mixture on the solid support is not desirable. In these instances, the combination of solution chemistry with polymer-assisted conversions can be an advantageous solution. Polymer-assisted synthesis in solution employs the polymer matrix either as a scavenger or for polymeric reagents. In both cases the virtues of solution phase and solid supported chemistry are ideally combined allowing for the preparation of pure products by filtration of the reactive resin. If several reactive polymers are used sequentially, multi-step syntheses can be conducted in a polymer-supported manner in solution as well. As a further advantage, many reactive polymers can be recycled for multiple use. 

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. 

Solid-phase synthesis Polymer-supported synthesis Polymer-supported solution synthesis Tag-assisted solution synthesis Combinatorial chemistry High-throughput synthesis Library Microreactor... 

Li, X., AbeU, C., Warrington, B.H. and Ladlow, M. (2003) Polymer-assisted solution phase synthesis of the antih3fperglycemic agent Rosiglitazone (Avandia ). Organic and Biomolecular Chemistry, 1, 4392-4395. 

The field of organic chemistry has seen the most extensive use of polymeric materials as aids in effecting chemical transformation and product isolation. Insoluble polymer supports have been used as handles to facilitate these functions. As chemical reagents can be bound to an insoluble polymer carrier and used in organic synthesis [117,118], polymer-bound reagents can also be used to assist in the purification step of solution-phase reactions [119,120]. The latter are known as scavenger resins. These are added to the reaction mixture upon completion of the reaction in order to quench and selectively bind to the unreacted reagents or by-products. The polymer-bound impurities are then removed firom the product by simple filtration to obtain pure compounds. For example, aminomethylated poly(styrene-co-divinyl benzene) can be used to remove acid chlorides, sulfonyl chlorides, isocyanates, thiocyanates, and proton. Similarly, 2-Chlorotrityl resins have been developed for the attachment of carboxylic acids, alcohols. 

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