This presentation reports the possibility to carry out simple solid phase coupling reactions not only by conventional thermal heating but also by microwave dielectric heating. Thus coupling of benzoic acid to Wang resin occurs under microwave irradiation within 3 h in excellent yield (>99%) as compared to 72 h at room temperature. However, a further increase of reaction rates in this particular coupling reaction is not possible due to a side reaction that occurs at higher temperatures.

The optimization of peptide nucleic acid (PNA) oligomer synthesis was carried out using Fmoc/acyl-protected monomers on NovaSyn® hydroxy-Tentagel resin and HATU/DIPEA/lutidine activation. The sequences H-Leu-ttttt- Gly-NH2 (1) and H-Gly-cgg-act-aag-tcc-att-gc-Gly-NH2 (2) were prepared and characterized by electrospray mass spectrometry

The Rink-linker (1a) [1] and analogous linkers like 1b [2] and 1c [3] are commonly used not only in peptide chemistry, but also in combinatorial chemistry, for grafting components with a carboxylic group onto the solid phase. Once assembled, the synthesis products are released into solution as carboxamides by acid treatment.

The growing speed of biological evaluation of potential drug substances during the past years has imposed the need to develop new methods for the fast and efficient generation of new chemical entities. In general, chemical libraries containing large numbers of compounds may be prepared either on polymer supports or in solution. The use of supported reagents combines the advantages of polymer-supported reactions (e.g. allowing the application of a large excess of the reagent without the need for additional purification steps) with the benefits of solution phase chemistry (e.g. the ease of monitoring the progress of the reaction by simply applying LC-MS or TLC techniques). While, many solid-supported reagents have been described, only a few have been used in combinatorial chemistry. Furthermore, multi-step sequences using polymer-supported reagents are rare, although there is a growing interest in sequestering agents on solid supports. Recent work in our group has focussed on the development of orchestrated multi-step methods using polymer-supported reagents for the preparation of chemical compound libraries.

A library of 42 diverse propargylamines was prepared using a parallel solution phase synthesis approach. The compounds resulting from the Mannich reaction of acetylenes, paraformaldehyde and secondary amines in the presence of copper(I)-chloride were purified by Solid Phase Extraction.

The amidation of a benzoic acid derivative attached to solid support via the T1 triazene linkage has been described. In the presence of a tin amide reagent, smooth amidations take place with primary and secondary amines to give benzamides. Anilines failed under the reaction condition employed. The progress and the success of the reaction were monitored by 1H NMR spectroscopy using a novel direct cleaving method.

A new variant of the Baylis-Hillman reaction based on lithium phenylselenide is adapted to Solid Phase Organic Synthesis (SPOS). Scope and limitations are studied using four polymer bound aldehydes.

The utility of hydroxy-(2-chlorophenyl)methyl polystyrene resin in solid phase synthesis is demonstrated. Methods are given for the immobilization and cleavage of acids and phenols.

Ring closing metathesis has been performed for the first time on a soluble poly(ethylene glycol) supported substrate in the presence of Grubbs' catalyst and provided in good yields 6-, 7- and 8-membered ring aminoacid derivatives. The presence of the polymer required the use of a higher amount of ruthenium complex but the addition of a cofactor such as 1-octene improved the turnover of the catalyst. On the other hand, a Schiff base protected glycine supported on a poly(ethylene glycol) reacted readily with various electrophiles in the presence of an inorganic base under microwave activation.

PAMAM dendrimers have been used to scavenge unreacted and excess reagents in synthesis.