Combinatorial libraries modular

Figure 11 Examples of unnatural modular polyketides. These compounds are part of a combinatorial library that was engineered using DEBS and include single, double, and triple modifications in modules 2, 3, 5, and 6.

In contrast, the Hoveyda and Snapper groups reported the efficient catalysis of silver acetate complexes of imine 204.86 These authors first established the superior performance of IV-ort/zo-methoxyaniline-substituted imines in the reaction with Danishefsky diene 195. Because of the modular nature of ligand 206, optimization of its structure could be achieved by surveying a combinatorial library of amino acid derivatives. The /-isoleucine para-methoxyaniline conjugate 206 proved the best. This ligand facilitated full conversion within 2-3 h with high yield and enantioselectivity (Scheme 2.53). 

In addition, their ease of synthesis and modular nature allows for a simple tuning of the catalytic activity through the synthesis of combinatorial libraries of catalysts, thus allowing optimization of their structure with respect to the substrate and reaction under investigation. 

Through the synthesis of parallel combinatorial libraries, Jacobsen and coworker discovered a new dass of catalysts for the Strecker reaction [15]. Because of its modular assembly, the new catalyst type was amenable to solid-phase synthesis and fast preparation, screening, and lead optimization were feasible. The best catalyst candidate afforded the Strecker product from N-allylbenzaldimine in 78% yield and 91% ee. Catalyst 21 was prepared as the soluble variant of the optimized candidate and proved to be an effective catalyst for a range of imine derivates 20, affording aromatic amino nitriles 22 in moderate to good yields (65-92%) and high enantioselectivities (70-91% ee) (Scheme 30.4). In addition, aliphatic aldimines 20... 

There are certain catalyst systems which appear to be more amenable to combinatorial studies than others. For example, libraries of small peptides as ligands are particularly easy to prepare (e.g., on solid supports), and due to their modular nature high diversity is possible. High diversity is also readily achieved when using mixtures of two or more chiral monodentate ligands.122 This novel approach offers many perspectives. 

Prior to their work with the Strecker reaction the Jacobsen group reported a combinatorial approach to the discovery of coordination complexes (29). A modular approach was taken in the synthesis of libraries of potential ligands for transition metals. Four variable components were used. Two amino acids were placed at positions 1 and 2, with a turn element connecting these groups (Scheme 9). The... 

Knappik, A., Ge, L., Honegger, A., Pack, P., Fischer, M., Wellnhofer, G., et al. (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus framework and CDRs randomized with trinucleotides. J. Mol. Biol. 296,57-86. 

Until the biosynthesis of aromatic polyketides can be controlled as precisely as modular PKSs, the most likely utility for this class of PKS is in the generation of libraries to screen for new activities. Due to the highly reactive nature of the aromatic polyketide backbones, a variety of cyclization patterns have been created through combinatorial biosynthesis with aromatic PKS gene clusters... 

DeWitt SH, Bear BR, Brussolo JS, Duffield MJ, Hogan EM, Kibbey CE, Mac Donald AA, Nickell DG, Rhoton RL, Robertsen GA, A modular system for combinatorial and automated synthesis. In Chaiken IM, Janda KD, eds., Molecular Diversity and Combinatorial Chemistry Libraries and Drug Discovery, ACS Conference Proceedings Series, Washington DC, American Chemical Society, pp. 188-198, 1996. 

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