Synthesis PASP

An alternative approach towards the PASP synthesis of isocyanides was developed by Bradley [100,101]. It involved the use of a polymer-supported sul-fonyl chloride in the presence of base to afford the dehydration of formamides (Scheme 21). The formamides required could be easily prepared by reaction of the corresponding amines with a formylated benzotriazole resin. Opti-... 

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).

Scheme 15.3 PASP synthesis of epothilone C, final steps.

Polymer-supported Synthetic Methods - Solid-phase Synthesis (SPS) and Polymer-assisted Solution-phase (PASP) Synthesis... 

II. Polymer-assisted solution phase synthesis (PASP synthesis)... 

PASP synthesis can be divided into two main approaches these being (a) the use of supported reagents and scavengers, and (b) the adoption of a catch-and-release strategy (Figure 1). Both of these techniques allow the production of clean products, without the need to resort to traditional purification techniques, such as column chromatography. In an ideal case, the incubation of a substrate with a supported reagent causes its complete transformation into a new chemical entity, with any... 

PASP Synthesis Approaches to Biologically Active Compounds... 

PASP Synthesis in the Library Production of Biologically Active Small Molecules... 

Scheme 5 PASP synthesis to a library of natural products related to polysphorin 19, illustrating key Sharpless asymmetric oxidation...

Scheme 7 Use of PASP synthesis for the preparation of a peptidic library...

The use of PASP synthesis in medicinal chemistry programmes to date has been extensively exploited by Parlow et previously at Pharmacia, in their search... 

Automated PASP Synthesis of Biologically Active Molecules... 

Stepwise Automation of PASP Synthesis in Batch Mode... 

The adoption of PASP synthesis presents the opportunity for in-Une purification strategies, through the use of supported scavengers or reagents and catch-and-release strategies. In this way, conventional purification techniques such as aqueous workups and column chromatography can be eliminated. In addition, the use of PASP synthesis reduces the vast number of traditional synthetic manipulations to a series of repetitive incubations and subsequent filtrations, which are in principle well suited to automated processing. 

Recently, a number of publications have dealt with the synthesis of drug-like molecules via fully automated PASP (auto-PASP) synthesis. This scenario entails the use of a series of immobilised reagents and scavenger reagents to perform a variety of sequential synthetic transformations in a common solvent. Each of the transformations... 

Another example of fully automated PASP synthesis is the preparation of a 192-member 2D array of 1,5-biaryl pyrazoles. " The 1,5-biaryl pyrazole moiety is found in a number of important pharmaceuticals, such as the selective COX-2 inhibitor Celecoxib and the nonsteroidal antiinflammatory agent Tepoxaline. The synthetic route to the 1,5-biaryl pyrazoles, exemplified by the library member 42... 

Figure 12 Catch-and-release PASP synthesis approach to heterocyclic thioethers...

The polymer-assisted solution-phase (PASP) synthesis of a 192-member group of 1,5-biaryl pyrazoles from 1,3-diketones and 4-hydrazinobenzoic acid as precursors has been reported <2004JC0332>. Condensation of aromatic or aliphatic esters with resin-supported sulfonamides 527, followed by cyclization with hydrazines, activation with trimethylsilyldiazomethane, and cleavage using amines, provided highly substituted, isomeric pyrazoles 528 and 529 (Scheme 63) <20000L2789>. 

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