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Total synthesis of (±)-fumimycin and analogues for biological evaluation as peptide deformylase inhibitors.

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 ?,?-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.

SUBMITTER: Zaghouani M

PROVIDER: S-EPMC6759494 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Total synthesis of (±)-fumimycin and analogues for biological evaluation as peptide deformylase inhibitors.

Zaghouani Mehdi M Bögeholz Lena A K LAK Mercier Evan E Wintermeyer Wolfgang W Roche Stéphane P SP

Tetrahedron 20190327 24

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. ...[more]

PMID: 31555018

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