Synthesis ofβ3-Homophenylalanine-Derived Amino Acids and Peptides bySuzuki Coupling in Solution and on Solid Support

β-Peptides and, to a certain extent, also mixed α,β-peptides, are resistant to degradation by a variety of proteolytic enzymes that rapidly degrade natural α-peptides. This is one of many characteristics that make β-peptides an attractive class of compounds for drug-discovery studies. On the other hand, modern organometallic reactions such as the Suzuki–Miyaura cross-coupling have become standard tools in industry laboratories to derivatize side chains of α-peptidic compounds to build up libraries of unnatural peptides. Combining both features, we prepared (4-bromo)-β3-homophenylalanine derivatives 3–5 and 12 as precursors for Suzuki–Miyaura couplings. From these bromo compounds, we synthesized biaryl-substituted β-homoamino acids 6, and analogs 13 and 15 of the anti-AIDS drug Saquinavir.