Combinatorial chemistry opens up new possibilities for research in medicinal chemistry in both the search for lead structures and their rapid optimization.['] Nevertheless, though many peptides are already the first milestones along this path, the optimization of sequences suitable for their combinatorial synthesis is still hardly a straightforward task.['] The synthesis strategy must take into account the compatibility and interplay of the spacers between resin and molecular scaffold, the protecting groups, and the derivatization reactions. The number, diversity and availability of nonpeptidic scaffolds is, at present, still very limited. The design of new and structurally highly diversified nonpeptide scaffolds is a prerequisite for encompassing the widest possible range of We are interested in conformationally fixed amino acid units, which can be used in a variety of ways, both to generate compound libraries and to optimize targeted lead structures by means of parallel synthesis.
In particular these structural elements should replace peptide sequences and/or pre-organize pharmacophores or other residues.[4. 61 We report here on the amino acid equivalent 1, which contains a cis-decalin partial structure (2) within a bile acid skeleton and, formally, mimics a tetrapeptide. In the form of derivative 3 it should be highly suitable for combinatorial syntheses. In 1 the two &-related OH functions on the a-face of chenodeoxycholic acid (4) are used. Separated in each case by a spacer, the