Schumacher, Christian Eric, Rausch, Marvin ORCID: 0000-0003-1562-4337, Greven, Tobias, Neudorfl, Joerg-Martin, Schneider, Tanja and Schmalz, Hans-Guenther ORCID: 0000-0003-0489-1827 (2022). Total Synthesis and Antibiotic Properties of Amino-Functionalized Aromatic Terpenoids Related to Erogorgiaene and the Pseudopterosins. Eur. J. Org. Chem., 2022 (26). WEINHEIM: WILEY-V C H VERLAG GMBH. ISSN 1099-0690
Full text not available from this repository.Abstract
Following a concept recently introduced by Hergenrother,([6]) the present study addresses the question of whether certain antimicrobially active aromatic (marine) natural products can be converted into more potent broad-spectrum antibiotics by introducing an aminoalkyl side chain. To this end, phenolic mono- and sesquiterpenoids (incl. carvacrol, xanthorrhizol, and 7-hydroxycalamene) as well as the diterpenes 7-hydroxyerogorgiaene and 9-deoxypseudopterosin A were converted into amino-functionalized analogs that display either an amino-methyl or a 2-amino-ethoxy substituent in place of (or next to) the OH group. This was achieved either by Pd-catalyzed nitromethylation/reduction of the aryltriflates, by O-alkylation of the phenols with bromoacetonitrile and subsequent reduction, or by ortho-hydroxymethylation/amination. During the study, an efficient enantioselective total synthesis of 7-hydroxyerogorgiaene (8 steps, 29 % overall yield) and 9-deoxypseudopterosin A (9 steps, 30 % overall yield) was elaborated using an asymmetric cobalt-catalyzed hydrovinylation (91 % ee) of 3-methoxy-4-methyl-styrene as the chirogenic step. Other important C-C bond forming steps include a Pd-catalyzed Suzuki cross-coupling and diastereoselective Lewis acid-mediated cyclization reactions. A total of 16 amino derivatives of natural products were prepared and subsequently tested for their antibacterial properties. Some of the diterpene-derived amines showed high efficacy, not only against Gram-positive (S. aureus SG511, S. aureus HG003, B. subtilis 168; MIC=0.5 to 2 mu g/ml), but also against Gram-negative bacterial strains (E. coli K12; E. coli I-11276b; MIC=8 to 32 mu g/ml). This clearly supported the underlying working hypothesis.
Item Type: | Journal Article | ||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-674344 | ||||||||||||||||||||||||||||
DOI: | 10.1002/ejoc.202200058 | ||||||||||||||||||||||||||||
Journal or Publication Title: | Eur. J. Org. Chem. | ||||||||||||||||||||||||||||
Volume: | 2022 | ||||||||||||||||||||||||||||
Number: | 26 | ||||||||||||||||||||||||||||
Date: | 2022 | ||||||||||||||||||||||||||||
Publisher: | WILEY-V C H VERLAG GMBH | ||||||||||||||||||||||||||||
Place of Publication: | WEINHEIM | ||||||||||||||||||||||||||||
ISSN: | 1099-0690 | ||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/67434 |
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