Details
| Original language | English |
|---|---|
| Pages (from-to) | 6935-6939 |
| Number of pages | 5 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 54 |
| Issue number | 23 |
| Publication status | Published - 1 Jun 2015 |
Abstract
Abstract The tedanolides are biologically active polyketides that exhibit a macrolactone constructed from a primary alcohol. Since polyketidal transformations only generate secondary alcohols, it has been hypothesized by Taylor that this unique lactone could arise from a postketidal transesterification. In order to probe this hypothesis and to investigate the biological profile of the putative precursor of all members of the tedanolide family, we embarked on the synthesis of desepoxyisotedanolide and its biological evaluation in comparison to desepoxytedanolide. The biological experiments unraveled a second target for desepoxytedanolide and provided evidence that the proposed transesterification indeed provides a survival advantage for the producing microorganism. A step in the right direction: Desepoxyisotedanolide, a hypothetical biosynthetic precursor of the tedanolide desepoxytedanolide, was synthesized. Biological studies of the two macrolactones revealed an additional cellular target for desepoxytedanolide, as well as evidence that the proposed isomerization of the precursor provides a survival advantage for the producing microorganism.
Keywords
- antitumor agents, macrolactones, natural products, polyketides, tedanolide
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- General Chemistry
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In: Angewandte Chemie - International Edition, Vol. 54, No. 23, 01.06.2015, p. 6935-6939.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - The synthesis and biological evaluation of desepoxyisotedanolide and a comparison with desepoxytedanolide
AU - Naini, Arun
AU - Muthukumar, Yazh
AU - Raja, Aruna
AU - Franke, Raimo
AU - Harrier, Ian
AU - Smith, Amos B.
AU - Lee, Dongjoo
AU - Taylor, Richard E.
AU - Sasse, Florenz
AU - Kalesse, Markus
N1 - Publisher Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Abstract The tedanolides are biologically active polyketides that exhibit a macrolactone constructed from a primary alcohol. Since polyketidal transformations only generate secondary alcohols, it has been hypothesized by Taylor that this unique lactone could arise from a postketidal transesterification. In order to probe this hypothesis and to investigate the biological profile of the putative precursor of all members of the tedanolide family, we embarked on the synthesis of desepoxyisotedanolide and its biological evaluation in comparison to desepoxytedanolide. The biological experiments unraveled a second target for desepoxytedanolide and provided evidence that the proposed transesterification indeed provides a survival advantage for the producing microorganism. A step in the right direction: Desepoxyisotedanolide, a hypothetical biosynthetic precursor of the tedanolide desepoxytedanolide, was synthesized. Biological studies of the two macrolactones revealed an additional cellular target for desepoxytedanolide, as well as evidence that the proposed isomerization of the precursor provides a survival advantage for the producing microorganism.
AB - Abstract The tedanolides are biologically active polyketides that exhibit a macrolactone constructed from a primary alcohol. Since polyketidal transformations only generate secondary alcohols, it has been hypothesized by Taylor that this unique lactone could arise from a postketidal transesterification. In order to probe this hypothesis and to investigate the biological profile of the putative precursor of all members of the tedanolide family, we embarked on the synthesis of desepoxyisotedanolide and its biological evaluation in comparison to desepoxytedanolide. The biological experiments unraveled a second target for desepoxytedanolide and provided evidence that the proposed transesterification indeed provides a survival advantage for the producing microorganism. A step in the right direction: Desepoxyisotedanolide, a hypothetical biosynthetic precursor of the tedanolide desepoxytedanolide, was synthesized. Biological studies of the two macrolactones revealed an additional cellular target for desepoxytedanolide, as well as evidence that the proposed isomerization of the precursor provides a survival advantage for the producing microorganism.
KW - antitumor agents
KW - macrolactones
KW - natural products
KW - polyketides
KW - tedanolide
UR - http://www.scopus.com/inward/record.url?scp=84930507588&partnerID=8YFLogxK
U2 - 10.1002/anie.201501526
DO - 10.1002/anie.201501526
M3 - Article
C2 - 25914374
AN - SCOPUS:84930507588
VL - 54
SP - 6935
EP - 6939
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 23
ER -