Total synthesis of (±)-fumimycin and analogues for biological evaluation as peptide deformylase inhibitors. Issue 24 (14th June 2019)

• Record Type: Journal Article
• Authors: Zaghouani, Mehdi; Bögeholz, Lena A.K.; Mercier, Evan; Wintermeyer, Wolfgang; Roche, Stéphane P.
• Is Part Of: Tetrahedron. Volume 75:Issue 24(2019)
• Page Start: 3216
• Page End: 3230
• Publication Date: 2019-06-14
• Subjects: (±)-Fumimycin -- Peptide deformylase inhibitors -- Total synthesis -- Intramolecular aza-Friedel–Crafts -- Metal-binding motifs -- Siderophores; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2019.03.037
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: A concise 7-step total synthesis of (±)-fumimycin in 11.6% overall yield is reported. An acid-catalyzed intramolecular aza-Friedel–Crafts cyclization was developed to construct the benzofuranone skeleton of the natural product bearing an α, α-disubstituted amino acid moiety in a single step. Regioselective chlorination followed by a Suzuki–Miyaura cross-coupling rapidly enabled the preparation of a library of analogues which were evaluated against peptide deformylase for antibacterial activity. Graphical abstract: Image 1