Applications combinatorial chemistry

CombiCHEM System (Fig. 3.9) For small-scale combinatorial chemistry applications, this barrel-type rotor is available. It can hold two 24- to 96-well microtiter plates utilizing glass vials (0.5-4 mL) at up to 4 bar at 150 °C. The plates are made of Weflon (graphite-doped Teflon) to ensure uniform heating and are sealed by an inert membrane sheet. Axial rotation of the rotor tumbles the microwell plates to admix the individual samples. Temperature measurement is achieved by means of a fiber-optic probe immersed in the center of the rotor. 

As demonstrated in the previous sections of this review, microwave-assisted reactions allow rapid product generation in high yield under uniform conditions. Therefore, they should be ideally suited for parallel synthesis and/or combinatorial chemistry applications. The first example of parallel reactions performed under micro-wave irradiation conditions involved the nucleophilic substitution of an alkyl iodide with 60 diverse piperidine or piperazine derivatives (Scheme 12.22) [71]. Reactions were performed in a multimode microwave reactor in individual sealed polypropy-... 

Eksterowicz, J. E., Evensen, E., Lemmen, C., et al. (2002) Coupling structure-based design with combinatorial chemistry application of active site derived pharmacophores with informative library design. J. Mol. Graph. Model. 20, 469-477. 

S. K. Sarkar, R. S. Garigipati, J. L. Adams and P. A. Keifer, An NMR method to identify nondestructively chemical compounds bound to a single solid-phase-synthesis bead for combinatorial chemistry applications, J. Am. Chem. Soc., 1996, 118, 2305-2306. 

Storer, R. Solution-Phase Synthesis in Combinatorial Chemistry Applications in Drug Discovery, Drug Discovery Today 1996,1, 248. 

Storer, R. 1996. Solution-phase synthesis in combinatorial chemistry applications in drug discovery. Drug Discovery Today, 1,248-254. 

Martin, J.F., presentation in IBC s Molecular Diversity and Combinatorial Chemistry - Applications for Drug Lead Discovery, San Diego, CA, U.S.A., 1996. 

Lin M, Shapiro MJ, Mixture analysis in combinatorial chemistry. Application of diffusion-resolved NMR spectroscopy, J. Org. Chem., 61 7617-7619, 1996. 

Weber, L. Evolutionary combinatorial chemistry application ofgenetic algorithms, Drag... 

Yan, B., Yan, H. Combination of single bead FTIR and chemometrics in combinatorial chemistry Application of the multivariate calibration method in monitoring solid-phase organic synthesis J. Comb. Chem., 2001, 3, 78-84... 

For combinatorial chemistry applications, high-quality FT-Raman spectra can be obtained directly from resin beads, i.e., no cleavage of the molecules from the polymeric support is necessary. This is shown in Fig. 5, where the spectra of TentaGel S beads coupled via a trityl linker with Fmoc-protected tryptophan and the native aminoethyl TentaGel S beads are overlaid. As expected, significant differences in the spectra occur in the spectral region between 1620 and 1500 cm-1 where aromatic rings show pronounced Raman activity. 

Various types of PSRs are described in the following sections. However, rather than classify these reagents by the type of support or by functionality, a classification based on the method of preparation is used here, with the focus on the most commonly employed techniques. Furthermore, rather than providing an exhaustive list of all PSRs described in the literature, the aim of this chapter is to provide an understanding of the principles of preparation and application of such reagents, with a special focus on important reactions and on the combination of several PSRs in one synthetic sequence or, where possible, in one pot. The latter is a rather novel and highly interesting aspect of combinatorial chemistry applications. 

This chapter aims to present an overview on the main peptide bond modifications which have been proposed in the recent years. The solution- and solid-phase synthesis of the new synthetic oligomers, the methods for their characterization, and their biological and folding properties will be discussed. Particular emphasis will be given to those modifications which are suitable for combinatorial chemistry applications and developments. 

Combinatorial Chemistry Applications on a Solid Phase (CCSP)... 

---