Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide
Ng, Kenneth K-H
Millican, David C
Dalby, Stephen M
Angewandte Chemie International Edition
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Paterson, I., Ng, K. K., Williams, S., Millican, D. C., & Dalby, S. M. (2014). Total Synthesis of the Antimitotic Marine Macrolide (−)-Leiodermatolide. Angewandte Chemie International Edition, 53 2692-2695. https://doi.org/10.1002/anie.201310164
Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.2 % yield) based on a convergent sequence of palladium-mediated fragment assembly and macrolactonization. Boron-mediated aldol reactions were used to configure the three key fragments 2, 5, and 6 by employing the appropriate enantiomer of the lactate-derived ketone 7.
aldol reaction, antitumor agents, cross-coupling, macrolides, total synthesis
This research was supported by a SCAST postgraduate research scholarship (K.K.-H.N.), the Todd-Raphael Fund (S.W.), and Clare College, Cambridge (S.M.D.). We thank Dr. Amy Wright (HBOI, Florida Atlantic University) for helpful discussions and the EPSRC UK National Mass Spectrometry Facility at Swansea University.
External DOI: https://doi.org/10.1002/anie.201310164
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246209
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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