ABSTRACT
Method Based on Thermomorphic Biphasic Organic Solutions.............604 30.3 Electrolytic Cyclization of Dipeptides Involving Proline-Moiety
for Construction of Conformation-Constrained Peptidomimetics ..........611 References .........................................................................................................616
Systematic synthesis of peptides and peptidomimetics plays an important role in their structure elucidation and estimation of active conformations in target receptors. In order to approach the final goal of structure analysis of peptides, synthetic methodology based on combinatorial, high-throughput peptide synthesis may be employed to explore adequate peptide sequences among the large number of oligopeptides at hand. Furthermore, systematic synthesis of conformation-constrained peptidomimetics provides important structural information on the native and biologically active peptides. This chapter provides information about (a) a new methodology for liquid-phase peptide synthesis using thermomorphic biphasic organic solutions, and (b) a new anodic method for the introduction of functional groups for the conformation control of proline moieties that would enable regulation of secondary structures of several kinds of peptides. In the first part of the chapter, convenient synthetic methods for oligopeptides are introduced. Combinations of typical organic solvents composed of cyclohexane and qualified aprotic polar organic solvents were found to realize an effective, biphasic
thermomorphic system in arbitrary ratios of upper and lower phases that enable a practical application of a liquid-phase peptide synthesis. In the second part, a new synthetic method of bicyclic dipeptidomimetics is introduced to obtain several kinds of conformation-constrained synthetic peptidomimetics.
