title: Solution versus solid-phase cyclization strategies for large sidechain lactam-bridged peptides: a comparative study.
abstract: A 22-residue peptide with a sidechain lactam bridge involving 18 residues (60-atom cycle) has been synthesized. Three different protection schemes using Fmoc/tBu/cyclohexyl, Fmoc/tBu/allyl or Boc/Bzl/ fluorenylmethyl protecting group combinations have been explored for the solid phase of the linear precursors, which have been subsequently cyclized in solution or in the solid phase. Cyclization yields in solution have been consistently better than on solid phase; however, the solid-phase strategy requires fewer purification steps and therefore global yields are comparable.
authors.affiliation: Department of Organic Chemistry, University of Barcelona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Camarero
authors.forename: J J
authors.initials: JJ
authors.lastname: Cairó
authors.forename: E
authors.initials: E
authors.lastname: Giralt
authors.forename: D
authors.initials: D
authors.lastname: Andreu
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D008722:Methods; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D012996:Solutions
chemical_list: D007202:Indicators and Reagents; D007769:Lactams; D010456:Peptides, Cyclic; D012996:Solutions