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Total synthesis and biological evaluation of aseries of macrocyclic hybrids and analogues of the antimitotic natural products Dictyostatin,Discodermolide, and Taxol
| Title: | Total synthesis and biological evaluation of aseries of macrocyclic hybrids and analogues of the antimitotic natural products Dictyostatin,Discodermolide, and Taxol. |
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| Name(s): |
Paterson, Ian Naylor, G. J. Gardner, Nicola M. Guzman, Esther A. Wright, Amy E. |
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| Type of Resource: | text | |
| Genre: | Article | |
| Date Issued: | 2011 | |
| Publisher: | Wiley | |
| Place of Publication: | Weinheim, Germany | |
| Physical Form: | ||
| Extent: | 16 p. | |
| Language(s): | English | |
| Identifier: | FA00007463 (IID), 10.1002/asia.201000541 (doi) | |
| Note(s): |
The design, synthesis, and biological evaluation of a series of hybrids and analogues of the microtubule-stabilizing anticancer agents dictyostatin, discodermolide, and taxol is described. A 22-membered macrolide scaffold was prepared by adapting earlier synthetic routes directed towards dictyostatin and discodermolide, taking advantage of the distinctive structural and stereochemical similarities between these two polyketide-derived marine natural products. Initial endeavors towards accessing novel discodermolide/dictyostatin hybrids led to the adoption of a late-stage diversification strategy and the construction of a small library of methyl-ether derivatives, along with the first triple hybrids bearing the side-chain of taxol or taxotere attached through an ester linkage. Biological assays of the anti-proliferative activity of these compounds in a series of human cancer cell lines, including the taxol-resistant NCI/ADR-Res cell line, allowed the proposal of various structure–activity relationships. This led to the identification of a potent macrocyclic discodermolide/dictyostatin hybrid and its C9 methoxy derivative , accessible by an efficient total synthesis and with a similar biological profile to dictyostatin. Florida Atlantic University. Harbor Branch Oceanographic Institute contribution 1818 This manuscript is an author version with the final publication available at http://www.interscience.wiley.com/ and may be cited as: Paterson, I., Naylor, G. J., Gardner, N. M., Guzmán, E., & Wright, A. E. (2011). Total synthesis and biological evaluation of a series of macrocyclic hybrids and analogues of the antimitotic natural products Dictyostatin, Discodermolide, and Taxol. Chemistry – An Asian Journal, 6(2), 459-473. doi:10.1002/asia.201000541 |
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| Subject(s): |
Macrolides Antimitotic Agents Natural products Tubulin |
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| Links: | http://dx.doi.org/10.1002/asia.201000541 | |
| Persistent Link to This Record: | http://purl.flvc.org/fau/fd/FA00007463 | |
| Host Institution: | FAU |
