title: A novel protecting/activating strategy for beta-hydroxy acids and its use in convergent peptide synthesis.
abstract: beta-Hydroxy acids were reacted with hexafluoroacetone and carbodiimides to give carboxy-activated six-membered lactones in good yields. On reaction with amines, the corresponding amides were obtained. We demonstrate the following applications of this protecting/activating strategy: preparation of carboxamides in solution and on solid phase (both normal and reverse mode); recovery and reuse of the excess material in solid-phase synthesis; and convergent solid-phase peptide synthesis (CSPPS) with peptide segments bearing C-terminal Ser or Thr with very low levels of epimerization (<1%, HPLC).
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Josep Samitier 1-5, E-08028 Barcelona, Spain. jan.spengler@irbbarcelona.com
authors.forename: Jan
authors.initials: J
authors.lastname: Spengler
authors.forename: Javier
authors.initials: J
authors.lastname: Ruíz-Rodríguez
authors.forename: Francesc
authors.initials: F
authors.lastname: Yraola
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
authors.forename: Manfred
authors.initials: M
authors.lastname: Winter
authors.forename: Klaus
authors.initials: K
authors.lastname: Burger
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives / Q000737:chemistry; D000577:Amides / Q000138:chemical synthesis; D000596:Amino Acids / Q000737:chemistry; D002234:Carbodiimides / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry; D005466:Fluorocarbons / Q000737:chemistry; D006880:Hydroxy Acids / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry; D008293:Malates / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis*; D006845:Hydrocarbons, Fluorinated
chemical_list: D000096:Acetone; D000577:Amides; D000596:Amino Acids; D002234:Carbodiimides; D005449:Fluorenes; D005466:Fluorocarbons; D006880:Hydroxy Acids; D007783:Lactones; D008293:Malates; D010455:Peptides; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; C030298:malic acid; C017366:hexafluoroacetone; D006845:Hydrocarbons, Fluorinated