title: Intramolecular Suzuki-Miyaura reaction for the total synthesis of signal peptidase inhibitors, arylomycins A(2) and B(2).
abstract: Development of the total syntheses of arylomycins A(1) and B(2) is detailed. Key features of our approach include 1) formation of 14-membered meta,meta-cyclophane by an intramolecular Suzuki-Miyaura reaction; 2) incorporation of N-Me-4-hydroxyphenylglycine into the cyclization precursor, which avoids the late-stage low-yielding N-methylation step; 3) segment coupling of a fully elaborated peptide side chain to the macrocycle, which makes the synthesis highly convergent. Overall, arylomycin A(2) was obtained in 13 steps from L-Tyr for the longest linear sequence, in 13 % overall yield. Arylomycin B(2) was synthesized in 10 steps from L-3-nitro-Tyr, in 10 % overall yield.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 1, avenue de la terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Dufour
authors.forename: Luc
authors.initials: L
authors.lastname: Neuville
authors.forename: Jieping
authors.initials: J
authors.lastname: Zhu
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001688:Biological Products; D003432:Cross-Linking Reagents; D009842:Oligopeptides; D011480:Protease Inhibitors; C488532:arylomycin A2