The synthesis and biological evaluation of desepoxyisotedanolide and a comparison with desepoxytedanolide.
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.
Institute for Organic Chemistry, Leibniz Universität Hannover and Centre of Biomolecular Drug Research (BMWZ), Schneiderberg 1B, 30655 Hannover (Germany).
Arun
A
Naini
Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, Braunschweig (Germany).
Yazh
Y
Muthukumar
Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, Braunschweig (Germany).
Aruna
A
Raja
Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, Braunschweig (Germany).
Raimo
R
Franke
Department of Chemistry & Biochemistry and Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556-567 (USA).
Ian
I
Harrier
Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 (USA).
Amos B
AB
Smith
College of Pharmacy, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon 443-749 (Korea).
Dongjoo
D
Lee
Department of Chemistry & Biochemistry and Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556-567 (USA).
Richard E
RE
Taylor
Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, Braunschweig (Germany).
Florenz
F
Sasse
Institute for Organic Chemistry, Leibniz Universität Hannover and Centre of Biomolecular Drug Research (BMWZ), Schneiderberg 1B, 30655 Hannover (Germany). markus.kalesse@oci.uni-hannover.de.
Markus
M
Kalesse
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry; D011817:Rabbits; D013329:Structure-Activity Relationship
D018942:Macrolides; C119775:tedanolide
antitumor agents; macrolactones; natural products; polyketides; tedanolide