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. 2013 Jun 7;15(11):2644-7.
doi: 10.1021/ol400904y. Epub 2013 May 10.

A redox economical synthesis of bioactive 6,12-guaianolides

Affiliations

A redox economical synthesis of bioactive 6,12-guaianolides

Bo Wen et al. Org Lett. .

Abstract

Syntheses of two 6,12-guaianolide analogs are reported within. The scope of the tandem allylboration/lactonization chemistry is expanded to provide a functionalized allene-yne-containing α-methylene butyrolactone that undergoes a Rh(I)-catalyzed cyclocarbonylation reaction to afford a 5-7-5 ring system. The resulting cycloadducts bear a structural resemblance to other NF-κB inhibitors such as cumambrin A and indeed were shown to inhibit NF-κB signaling and cancer cell growth.

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Figures

Figure 1
Figure 1
Examples of highly oxidized 6,12-guaianolides
Figure 2
Figure 2
NF-κB luciferase reporter assay in A549 cells. Compounds 22a-b were dosed at 20, 10, and 1 μM and PTL was dosed at 10 and 1 μM. Cells were induced with TNF-α (15 ng/mL) 30 min after molecule treatment, except NI control. Shown is the mean of triplicate data and error bars represent propagated standard deviation. NI = non-induced, I = induced.
Scheme 1
Scheme 1
An APKR approach to highly oxidized guaianolides
Scheme 2
Scheme 2
Generation of the allylboronates, Z:E ratios
Scheme 3
Scheme 3
A model system for the lactonization protocol
Scheme 4
Scheme 4
Synthesis of 6,12-guaianolide analogs 22a-b

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