title: Difficult macrocyclizations: new strategies for synthesizing highly strained cyclic tetrapeptides.
abstract: [reaction: see text] Cyclic tetrapeptides are an intriguing class of natural products. To synthesize highly strained cyclic tetrapeptides we developed a macrocyclization strategy that involves the inclusion of 2-hydroxy-6-nitrobenzyl (HnB) group at the N-terminus and in the "middle" of the sequence. The N-terminal auxiliary performs a ring closure/ring contraction role, and the backbone auxiliary promotes cis amide bonds to facilitate the otherwise difficult ring contraction. Following this route, the all-L cyclic tetrapeptide cyclo-[Tyr-Arg-Phe-Ala] was successfully prepared.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Wim D F
authors.initials: WD
authors.lastname: Meutermans
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Bourne
authors.forename: Simon W
authors.initials: SW
authors.lastname: Golding
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Horton
authors.forename: Marc R
authors.initials: MR
authors.lastname: Campitelli
authors.forename: David
authors.initials: D
authors.lastname: Craik
authors.forename: Martin
authors.initials: M
authors.lastname: Scanlon
authors.forename: Mark L
authors.initials: ML
authors.lastname: Smythe
mesh_terms: D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D003500:Cyclization; D007536:Isomerism; D009578:Nitrobenzenes / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D010782:Photolysis; D011487:Protein Conformation
chemical_list: D000577:Amides; D009578:Nitrobenzenes; D009842:Oligopeptides; D010456:Peptides, Cyclic