Teabag method

Teabag method, an approach in combinatorial peptide synthesis that uses parallel... 

Combinatorial libraries are prepared by the (1) parallel synthesis of arrays, (2) split-pool method, (3) biological method, or (4) spatially addressable parallel synthesis [74,78-80]. Parallel synthesis is carried out by the simultaneous synthesis of an array of different compounds. Several methods are available. In the multipin method, the peptide synthesis is carried out on polyethylene rods that have attached protected amino acids [81]. The amino acid sequence of a synthesized peptide on a particular pin depends on the order in which the amino acids are added. The number of products synthesized is the same as the number of pins. Another version of parallel synthesis, known as the teabag method, uses resin-filled bags in place of pins [74]. By pooling the resin portions from the appropriate bags, followed by redistribution and further coupling with a specific amino acid, a peptide library can be synthesized. The SPOT method uses a cellulose paper membrane as a solid support, which acts as an open reactor. Respective reagent solutions are pipetted onto several spots to synthesize as many peptides as the spots chosen [74,82]. 

Employing the teabag approach for parallel synthesis, the reagent mixture method, and the libraries from libraries concept, a wide range of different small molecule compounds was successfully prepared in our laboratory during the past decade. Starting from amino acids and short... 

This technique is still evolving. The favored approach at present is to submerge a small, known amount of suspension inside a secured Durapore (polyvinylidene fluoride) membrane pouch (Millipore Products, Bedford, MA) of suitable porosity in teabag fashion in a suitable dissolution medium using the USP Method 1 Paddle Apparatus. Optimization of experimental conditions (rate of agitation, volume and type of medium, temperature, etc.) must be established to achieve reproducible results. 

An elegant method for the solid-phase synthesis of quinolinone 9 derivatives has been developed by Pei et al. [43]. Using the teabag technology, the synthesis of a 4-amino-3,4-dihydro-2(l//)-quinolinone library was carried out through the rearrangement of /3-lactam intermediates on the solid phase. The condensation of o-nitrobenzaldehyde with a resin-bound amino acid yielded an imine that, following [2-1-2] cycloaddition with ketenes, afforded the -lactams (Fig. 3g). 

The supports used for these methods include standard resins, polymers packaged in permeable teabag -style containers [8], derivatized plastic pins [9], and membranes [10] (see Chapter 1). The solid supports are typically combined for the common deblocking and washing steps and then separated to perform couplings on individual portions of the support. 

Microwave heating has been used as a tool for the generation of a library of 625 peptoids (Scheme 4.18). The method, involving the synthesis of Af-alkylglycine oligomers, used a set of 10 commercially available primary amines as a source of chemical diversity. The synthetic steps wae carried out in teabags. The overall synthetic strategy involved an initial room temperature deprotection of Fmoc-protected Rink amide resin. This was followed by five repetitive acylation (35 °C for 30 s) and amination (90 °C for 90 s) steps in the microwave unit. Two sublibraries were... 

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