Organic Chemistry on Solid Supports

Abstract

AbstractUntil recently, repetitive solid‐phase synthesis procedures were used predominantly for the preparation of oligomers such as peptides, oligosaccharides, peptoids, oligocarbamates, peptide vinylogues, oligomers of pyrrolin‐4‐one, peptide phosphates, and peptide nucleic acids. However, the oligomers thus produced have a limited range of possible backbone structures due to the restricted number of building blocks and synthetic techniques available. Biologically active compounds of this type are generally not suitable as therapeutic agents but can serve as lead structures for optimization. “Combinatorial organic synthesis” has been developed with the aim of obtaining low molecular weight compounds by pathways other than those of oligomer synthesis. This concept was first described in 1971 by Ugi.[56f,g,59c] Combinatorial synthesis offers new strategies for preparing diverse molecules, which can then be screened to provide lead structures. Combinatorial chemistry is compatible with both solution‐phase and solid‐phase synthesis. Moreover, this approach is conducive to automation, as proven by recent successes in the synthesis of peptide libraries. These developments have led to a renaissance in solid‐phase organic synthesis (SPOS), which has been in use since the 1970s. Fully automated combinatorial chemistry relies not only on the testing and optimization of known chemical reactions on solid supports, but also on the development of highly efficient techniques for simultaneous multiple syntheses. Almost all of the standard reactions in organic chemistry can be carried out using suitable supports, anchors, and protecting groups with all the advantages of solid‐phase synthesis, which until now have been exploited only sporadically by synthetic organic chemists. Among the reported organic reactions developed on solid supports are Diels–Alder reactions, 1,3‐dipolar cycloadditions, Wittig and Wittig–Horner reactions, Michael additions, oxidations, reductions, and Pd‐catalyzed CC bond formation. In this article we present a comprehensive review of the previously published solid‐phase syntheses of nonpeptidic organic compounds.