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. 2008 Nov 13;51(21):6650-3.
doi: 10.1021/jm800979v. Epub 2008 Oct 8.

Improved synthesis of 6-epi-dictyostatin and antitumor efficacy in mice bearing MDA-MB231 human breast cancer xenografts

Julie L Eiseman  1 , Lihua Bai, Won-Hyuk Jung, Gustavo Moura-Letts, Billy W Day, Dennis P Curran
Affiliations

Improved synthesis of 6-epi-dictyostatin and antitumor efficacy in mice bearing MDA-MB231 human breast cancer xenografts

Julie L Eiseman et al. J Med Chem. .

Abstract

Structure-activity studies centered on the naturally occurring antitumor agent dictyostatin have recently identified several highly active epimers and analogues. From these compounds, 6- epi-dictyostatin was selected for scaleup preparation and evaluation in animals. Here we describe a new total synthesis that produced more than 30 mg of 6- epi-dictyostatin. The compound was found to have potent antitumor activity in SCID mice bearing MDA-MB231 human breast cancer xenografts.

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Figures

Figure 1
Figure 1
Retrosynthetic analysis of 6-epi-dictyostatin
Figure 2
Figure 2
Antitumor activity in MDA-MB231 human breast cancer xenograft-bearing C.B-17 SCID female mice (n = 10 animals per group) treated with 20 mg/kg iv q7dx3 6-epi-dictyostatin 1 (○) or paclitaxel (△), vehicle (▲), or no treatment (▽). Arrows inidicate the days of dosing.
Figure 3
Figure 3
Body weight changes in MDA-MB231 human breast cancer xenograft-bearing C.B.-17 SCID female mice (n = 10 animals per group) over the course of treatment with 20 mg/kg iv q7dx3 6-epi-dictyostatin 1 (○) or paclitaxel (△), vehicle (▲), or no treatment (▽). Arrows inidicate the days of dosing.
Scheme 1
Scheme 1
Fragment couplings and macrolactonization
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