Details
| Original language | English |
|---|---|
| Pages (from-to) | 4272-4284 |
| Number of pages | 13 |
| Journal | Chemistry - A European Journal |
| Volume | 21 |
| Issue number | 11 |
| Publication status | Published - 4 Feb 2015 |
Abstract
The total and semi-synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium Sorangium cellulosum, are reported. The thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards Mycobacterium tuberculosis. This study focuses on 1) thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacins A-C, 2) the roles of the thiazole ring, and 3) the hexyl side chain at C2. Semi-synthetic O-methylation at C17 suppressed the transacylations without a substantial loss of antibacterial activity. Exchanging the C17-C25 side chain for simplified hydrophobic chains led to complete loss of antibacterial activity. Exchange of the thiazole by an oxazole ring or removal of the hexyl side chain at C2 had no substantial effect on the biological properties.
Keywords
- antibiotics, lactones, natural products, synthesis design, total synthesis
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
Sustainable Development Goals
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In: Chemistry - A European Journal, Vol. 21, No. 11, 04.02.2015, p. 4272-4284.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Total and semi-syntheses of antimicrobial thuggacin derivatives
AU - Franke, Jana
AU - Bock, Martin
AU - Dehn, Richard
AU - Fohrer, Jörg
AU - Mhaske, Santosh B.
AU - Migliorini, Antonella
AU - Kanakis, Argyrios A.
AU - Jansen, Rolf
AU - Herrmann, Jennifer
AU - Müller, Rolf
AU - Kirschning, Andreas
PY - 2015/2/4
Y1 - 2015/2/4
N2 - The total and semi-synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium Sorangium cellulosum, are reported. The thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards Mycobacterium tuberculosis. This study focuses on 1) thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacins A-C, 2) the roles of the thiazole ring, and 3) the hexyl side chain at C2. Semi-synthetic O-methylation at C17 suppressed the transacylations without a substantial loss of antibacterial activity. Exchanging the C17-C25 side chain for simplified hydrophobic chains led to complete loss of antibacterial activity. Exchange of the thiazole by an oxazole ring or removal of the hexyl side chain at C2 had no substantial effect on the biological properties.
AB - The total and semi-synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium Sorangium cellulosum, are reported. The thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards Mycobacterium tuberculosis. This study focuses on 1) thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacins A-C, 2) the roles of the thiazole ring, and 3) the hexyl side chain at C2. Semi-synthetic O-methylation at C17 suppressed the transacylations without a substantial loss of antibacterial activity. Exchanging the C17-C25 side chain for simplified hydrophobic chains led to complete loss of antibacterial activity. Exchange of the thiazole by an oxazole ring or removal of the hexyl side chain at C2 had no substantial effect on the biological properties.
KW - antibiotics
KW - lactones
KW - natural products
KW - synthesis design
KW - total synthesis
UR - http://www.scopus.com/inward/record.url?scp=84923863254&partnerID=8YFLogxK
U2 - 10.1002/chem.201405874
DO - 10.1002/chem.201405874
M3 - Article
C2 - 25123591
AN - SCOPUS:84923863254
VL - 21
SP - 4272
EP - 4284
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 11
ER -