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Synthesis and biological evaluation of (-)-dictyostatin and stereoisomers

Shin, Y and Fournier, JH and Brückner, A and Madiraju, C and Balachandran, R and Raccor, BS and Edler, MC and Hamel, E and Sikorski, RP and Vogt, A and Day, BW and Curran, DP (2007) Synthesis and biological evaluation of (-)-dictyostatin and stereoisomers. Tetrahedron, 63 (35). 8537 - 8562. ISSN 0040-4020

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Abstract

Total syntheses of (-)-dictyostatin, 6,16-bis-epi-dictyostatin, 6,14,19-tris-epi-dictyostatin, and a number of other isomers and analogs are reported. Three main fragments-top, middle, and bottom-were first assembled and then joined by olefination or anionic addition reactions. After appending the two dienes at either end of the molecule, macrolactonization and deprotection completed the syntheses. The work proves both the relative and absolute configurations of (-)-dictyostatin. The compounds were evaluated by cell-based measurements of increased microtubule mass and antiproliferative activity, and in vitro tubulin polymerization assays as well as competitive assays with paclitaxel for its binding site on microtubules. These assays showed dictyostatin to be the most potent of the agents and further showed that the structural alterations caused from 20- to >1000-fold decreases in activity. © 2007 Elsevier Ltd. All rights reserved.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Shin, Y
Fournier, JH
Brückner, A
Madiraju, C
Balachandran, R
Raccor, BS
Edler, MC
Hamel, E
Sikorski, RP
Vogt, A
Day, BW
Curran, DPcurran@pitt.eduCURRAN
Date: 27 August 2007
Date Type: Publication
Journal or Publication Title: Tetrahedron
Volume: 63
Number: 35
Page Range: 8537 - 8562
DOI or Unique Handle: 10.1016/j.tet.2007.05.033
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0040-4020
PubMed Central ID: PMC2000856
PubMed ID: 18728696
Date Deposited: 02 May 2013 20:25
Last Modified: 02 Feb 2019 15:58
URI: http://d-scholarship.pitt.edu/id/eprint/18564

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