211745-08-3Relevant academic research and scientific papers
Convergent solution-phase combinatorial synthesis with multiplication of diversity through rigid biaryl and diarylacetylene couplings
Boger, Dale L.,Jiang, Weiqin,Goldberg, Joel
, p. 7094 - 7100 (2007/10/03)
The solution-phase synthesis of iminodiacetic acid diamide libraries linked to aryl iodides and their Pd-catalyzed dimerization are detailed. Mixtures containing 64 980 components are synthesized in only 4 steps from N- BOC-iminodiacetic acid anhydride (1) and 21 readily available starting materials, demonstrating the multiplication of diversity achievable by the convergent assembly of building blocks. Both biaryl formation and sequential Stille couplings with bis(tributylstannyl)-acetylene are utilized to dimerize the functionalized iminodiacetic acid diamide precursors resulting in product libraries with two sets of binding groups separated by variable length rigid linkers suitable for probing protein-protein interactions. Deconvolution libraries synthesized alongside the full mixtures allow for identification of active components.
Higher order iminodiacetic acid libraries for probing protein-protein interactions
Boger, Dale L.,Goldberg, Joel,Jiang, Weiqin,Chai, Wenying,Ducray, Pierre,Lee, Jae Kyoo,Ozer, Rachel S.,Andersson, Carl-Magnus
, p. 1347 - 1378 (2007/10/03)
Full details of the preparation of iminodiacetic acid diamide dimer (2040 compounds), trimer (560 compounds), and tetramer (1596 compounds) libraries by multistep convergent solution-phase synthesis for studying protein-protein interactions are provided. The libraries were assembled in a format providing small 8-10 compound mixtures and the deconvolution of many of the small mixtures to identify screening leads by resynthesis of the individual components have been conducted for 320 of the individual compounds to date. A representative example of the subsequent exploration of the structure-activity relationships for an identified receptor binding antagonist (200 additional individual compounds) and steps taken for potential elaboration to a receptor dimerization agonist are defined with preparation of representative linked dimers (70 compounds). Copyright (C) 1998 Elsevier Science Ltd.
Solution-phase combinatorial synthesis: Convergent multiplication of diversity via the olefin metathesis reaction
Boger, Dale L.,Chai, Wenying
, p. 3955 - 3970 (2007/10/03)
The solution-phase synthesis of iminodiacetic acid diamides functionalized with ω-alkenes and their dimerization via the olefin metathesis reaction in the preparation of mixture libraries are detailed. Libraries containing as many as 113,232 compounds prepared from only N-BOC- iminodiacetic acid anhydride (1), 15 amines, and 4 ω-alkene carboxylic acids illustrate the diversity that may be achieved by a convergent versus divergent combination of a small number of monomer building blocks that provides the multiplication of diversity typically associated with linear library syntheses including peptides, oligonucleotides and sequential template functionalizations. Unlike the divergent synthesis of such libraries which is amenable to solid-phase synthesis techniques, the convergent synthesis is especially well suited for solution-phase synthesis and is precluded by solid-phase techniques since the combining components typically would be on mutually exclusive phases.
Higher order iminodiacetic acid libraries for probing protein-protein interactions
Boger, Dale L.,Ducray, Pierre,Chai, Wenying,Jiang, Weiqin,Goldberg, Joel
, p. 2339 - 2344 (2007/10/03)
Higher order iminodiacetic acid diamide trimer (560 compounds) and tetramer libraries (1260 compounds) are described and were assembled in a convergent multistep solution-phase synthesis for use in studying protein- protein interactions.
