eprintid: 18564
rev_number: 18
userid: 1418
dir: disk0/00/01/85/64
datestamp: 2013-05-02 20:25:35
lastmod: 2019-02-02 15:58:47
status_changed: 2013-05-02 20:25:35
type: article
metadata_visibility: show
item_issues_count: 0
eprint_status: archive
creators_name: Shin, Y
creators_name: Fournier, JH
creators_name: Brückner, A
creators_name: Madiraju, C
creators_name: Balachandran, R
creators_name: Raccor, BS
creators_name: Edler, MC
creators_name: Hamel, E
creators_name: Sikorski, RP
creators_name: Vogt, A
creators_name: Day, BW
creators_name: Curran, DP
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creators_email: curran@pitt.edu
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creators_id: CURRAN
title: Synthesis and biological evaluation of (-)-dictyostatin and stereoisomers
ispublished: pub
divisions: sch_as_chemistry
full_text_status: public
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.
date: 2007-08-27
date_type: published
publication: Tetrahedron
volume: 63
number: 35
pagerange: 8537 - 8562
refereed: TRUE
issn: 0040-4020
id_number: 10.1016/j.tet.2007.05.033
pmcid: PMC2000856
pmid: 18728696
citation:   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     
document_url: http://d-scholarship-dev.library.pitt.edu/18564/1/licence.txt