Brief History of Combinatorial Chemistry

While combinatorial synthesis is a relatively new field of chemistry, Nature has been utilizing the same principles since the beginning. Although biologists had previously recognized the power of combinatorial chemistry, its application to problems relating to chemistry did not emerge until recently. Chemists' confidence in rational design has previously kept them away from systematic explorations in chemical synthesis. The rather dramatic developments in molecular biology and high-throughput...

Electrophilic Substitution in Combinatorial and Solidphase Synthesis

Jan-Gerd Hansel and Stephan Jordan 9.1 Reactions in which an electron-deficient reagent attacks a substrate and an electron-deficient leaving group is displaced are called electrophilic substitutions (SE). The most common leaving group is the proton. While the reaction is typical for aromatic systems, aliphatic substrates only react when hydrogens of sufficient acidity are available. This chapter focuses on the application of SE in the generation of chemical diversity. Compared with...

Analysis of Combinatorial Libraries

Combinatorial syntheses need fast and reliable analyses in order to determine the identity of products and intermediates in each step of a parallel reaction sequence. 6.3 Analysis of Combinatorial Libraries 217 Tab. 6.5. Analytical methods and their applications in combinatorial chemistry. Method Application FT-IR Characterization of resin-bound intermediates in reflection (ATR (ATR attenuated total reflectance) DRIFTS (DRIFTS diffuse reflectance infrared fourier transform spectroscopy)) NMR...

Prtocole Use Naldic Acide

1. 10, -78 - gt -20 C, DCM, 16h 0.16 eq., -78 -20 C, CH2CI2, 16 h R 6 examples 21 56-88 , gt 97 de Scheme 18.6. Stereoselective addition of chiral B enolates to resin-bound aldehydes. formed upon cleavage from the resin was obtained in poor yield. Moreover, isolation of the final product required chromatography since the crude reaction mixture was contaminated by oxazolidinone 19 . Optimal results for the solid-supported Evans aldol protocol were elaborated for soluble polyethylene glycol PEG...

Radiofrequency Tags

Microreactor System

One of the most successful automated solutions for the synthesis of encoded chemical libraries is utilizing electronic identification devices. Scheme 5.12 illustrates one such device - the radiofrequency RF identification ID tag. Similar Rectifier Trarumitter feceiver circuitry Scheme 5.12. Schematic of an RF memory chip useful for encoded synthesis. Scheme 5.12. Schematic of an RF memory chip useful for encoded synthesis. devices have been used for years to tag laboratory mice subcutaneously,...

Privileged Structures

The term ''privileged structures'' was introduced by Evans and coworkers for structural types of small molecules that are able to bind with high affinity to multiple classes of receptors 42 . Benzazepine analogs were found to be effective ligands for 768 27 Virtual Compound Libraries and Molecular Modeling Tab. 27.1. GPCR-like building blocks. Structurea GPCR likeness Structure Structure Structurea GPCR likeness Structure Structure a Building blocks were taken from the Available Chemicals...

OnVyn2 1sclg2H20NMP oW

Synthesis of a benzimidazole library via tin-mediated nitro reduction. cally accompany nitro reduction with SnCl2, which presents a potential problem with acid-sensitive polymer supports. Addition of a small amount of buffer such as sodium acetate often remedies this situation 35, 115 . DMF is the solvent of choice for tin reductions, but N-formylation of o-diaminobenzenes generated from 2-amino-substituted nitrobenzenes and subsequent cyclization to benzimidazoles has been...

Nucleophilic Substitution in Combinatorial and Solidphase Synthesis

Jan-Gerd Hansel and Stephan Jordan 8.1 Nucleophilic substitution SN reactions are widely used in combinatorial chemistry. Two reasons account for this prevalence first the potential to combine building blocks by SN and second the availability of building blocks that can participate in SN reactions. In addition, SN reactions are typically very reliable transformations, robust, and thus ideally suited for high-throughput synthesis of organic compounds. In this chapter the application of SN...

R r r r

Resin Linker attached Functional group linker Traceless linker special case of a monodirectional linker or e.g. A RCHO electrophiles and B RNH2 nucleophiles Fig. 4.5. Linker types for solid-phase synthesis 197 . tion of the linker before cleavage, such a system can be applied to monodirectional linkers, such as traceless linkers Sect. 4.5.5 or to multifunctional linkers Sect. 4.5.6 , as well as to cleavage-cyclization strategies. Recent applications of the Kenner linker have been shown in the...

List of Authors

Markus Albers Bayer AG Central Research D-51368 Leverkusen Germany Valery V. Antonenko Affymax Research Institute 3410 Central Expressway Santa Clara CA 95051 USA Bill Archibald H3-Technologies Inc. 1021 Grebe Street Foster City CA 94404 USA Istvan Bagyi ComGenex Inc. Bem rkp. 33-34 H-1024 Budapest Hungary Marcus Bauser Bayer AG Pharma Research PH-R-CR VII D-42096 Wuppertal Germany Kekule-Institut f r Organische Chemie und Biochemie Universit t Bonn Gerhard-Domagk-Stra e 1 D-53121 Bonn Germany...