Target-oriented library

We anticipate that the current shift in combinatorial chemistry libraries away from numerically large to more focused, target-oriented libraries will continue in the near future and that these hbraries will be helpful in developing ligands with improved binding characteristics. It is also plausible that such a shift may open efficient inhibitor and ligand discovery opportunities to academic laboratories. 

Centerpieces of combinatorial concepts include the synthesis of compound libraries instead of the preparation of single target compounds. Library synthesis is supplemented by approaches to optimize the diversity of a compound collection (diversity-oriented synthesis) and by efforts to create powerful interfaces between combinatorial synthesis and bioassays. 

Zheng, W. and Lampe, J. (2002) Combinatorial optimization approaches to the design of focused, diverse, and target class oriented libraries. Cambridge Healthtech Institute s Sixth Annual Cheminformatics, Philadelphia, PA. 

Rosania et al. [19] have shown this straightforward preparation to be advantageous for the transposition to a diversity-oriented, combinatorial approach to an organelle-targeted fluorescent library. Therefore, the condensation of 9 and 10 (Fig. 5.4) with pyrrolidine as a catalyst was performed in 96-well plates and the dehydration reaction was accelerated by microwave irradiation for 5 min to give 10-90% conversion. The resulting library compounds were analyzed using an LC-MS system with diode-array and fluorescence detectors and a fluorescence plate-reader to determine the absorption and emission maxima and the emission colors. 

The Ugi four-component reaction is currently the most investigated MCRs in both target-oriented [95] as well as diversity-oriented S3mthesis of compound libraries (for reviews, see [33-52]). As one of the rare truly and highly versatile... 

Fig. 17.3 Target-oriented approach and diversity-oriented fluorescence library approach...

The power of furan has long been appreciated in target-oriented synthesis and more recently in diversity-oriented synthesis. Schreiber has made elegant use of the embedded diversity in this heterocycle to build complex, natural product-like libraries <03SCI1613 04JA14095> (Scheme... 

Figure 4.1. Planning strategies and end goals involved in target-oriented synthesis, focused library synthesis (combinatorial synthesis), and diversity-oriented synthesis. The first two approaches use retrosynthetic analysis to design the synthesis of target compounds. Diversity-oriented synthesis uses forward synthetic analysis to produce libraries that occupy diffuse regions of chemical space.

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