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Total Synthesis and Biological Assessment of Novel Albicidins Discovered by Mass Spectrometric Networking
Author(s) -
von Eckardstein Leonard,
Petras Daniel,
Dang Tam,
Cociancich Stéphane,
Sabri Souhir,
Grätz Stefan,
Kerwat Dennis,
Seidel Maria,
Pesic Alexander,
Dorrestein Pieter C.,
Royer Monique,
Weston John B.,
Süssmuth Roderich D.
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201704074
Subject(s) - antimicrobial , drug discovery , tandem mass spectrometry , chemistry , combinatorial chemistry , mass spectrometry , antibacterial activity , bacteria , total synthesis , biological activity , computational biology , biology , stereochemistry , biochemistry , organic chemistry , chromatography , in vitro , genetics
Natural products represent an important source of potential novel antimicrobial drug leads. Low production by microorganisms in cell culture often delays the structural elucidation or even prevents a timely discovery. Starting from the anti ‐Gram‐negative antibacterial compound albicidin produced by Xanthomonas albilineans , we describe a bioactivity‐guided approach combined with non‐targeted tandem mass spectrometry and spectral (molecular) networking for the discovery of novel antimicrobial compounds. We report eight new natural albicidin derivatives, four of which bear a β‐methoxy cyanoalanine or β‐methoxy asparagine as the central α‐amino acid. We present the total synthesis of these albicidins, which facilitated the unambiguous determination of the (2 S ,3 R )‐stereoconfiguration which is complemented by the assessment of the stereochemistry on antibacterial activity.