title: Solid Phase Synthesis of beta-Peptoids: N-Substituted beta-Aminopropionic Acid Oligomers.
abstract: A solid-phase organic synthesis method has been developed for the preparation of N-substituted-beta-aminopropionic acid oligomers or beta-peptoids 1. Treatment of polymer-bound 4-(benzyloxy)benzyl acrylate 2 with primary amines afforded N-substituted beta-alanines 3. Polymer loadings and product conversions were determined by direct cleavage of resin-bound materials and measurement by (1)H NMR with an internal standard. The NMR method was used to establish loading of all resin-bound intermediates including acrylic acid. Acylation with acryloyl chloride followed by Michael addition of primary amines to the acrylamide allowed preparation of di-beta-peptoids. By a linear set of seven reactions, trimeric N-benzyl-beta-aminopropionic acid was prepared in 67% overall yield. Single-bead FT-IR microspectroscopy was used to acquire spectra of the resin bound mono-beta-peptoids, di-beta-peptoids, and acrylamide intermediates. A combinatorial library of defined mixtures of tri-beta-peptoids was prepared by mixing equimolar amounts of the mono-beta-peptoid resins and carrying them through two sequences of the acylation-Michael addition. The identity of a sample mixture was determined by LC-MS analysis of the cleavage product.
authors.affiliation: Monsanto Company, 800 North Lindbergh Boulevard, St. Louis, Missouri 63167.
authors.forename: Bruce C.
authors.initials: BC
authors.lastname: Hamper
authors.forename: Stephen A.
authors.initials: SA
authors.lastname: Kolodziej
authors.forename: Angela M.
authors.initials: AM
authors.lastname: Scates
authors.forename: Ronald G.
authors.initials: RG
authors.lastname: Smith
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Cortez