Dideoxyverticillin A Explained

Dideoxyverticillin A, also known as (+)-11,11′-dideoxyverticillin A, is a complex epipolythiodioxopiperazine^[1] initially isolated from the marine fungus Penicillium sp. in 1999.^[2] It has also been found in the marine fungus Bionectriaceae,^[3] and belongs to a class of naturally occurring 2,5-diketopiperazines.^[4]

Dideoxyverticillin A potently inhibits the tyrosine kinase activity of the epidermal growth factor receptor (median inhibitory concentration = 0.14 nM), exhibits antiangiogenic activity, and has efficacy against several cancer cell lines. Its reported anticancer mechanism is that it acts as a farnesyl transferase inhibitor. Dozens of semi-synthetic anticancer compounds have been made from dideoxyverticillin A. Dimeric derivatives are reported to have better anticancer activity.^[5]

The enantioselective first total synthesis of (+)-11,11′-dideoxyverticillin A, the structure of which contains many sterically congested, contiguous stereogenic centers as well as acid- and base-labile and redox-sensitive functionality, was biosynthetically inspired and achieved with high levels of chemical sophistication.^[6]

External links

• MIT News - 11,11′-Dideoxyverticillin
• Shi Y, Zhang Y, Ni Y, Shi G, Yang H . 11-脱氧轮枝菌素A引起前列腺癌PC3M细胞Caspase依赖的凋亡 . 11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells . zh . Sheng Wu Gong Cheng Xue Bao . 28 . 1 . 96–103 . January 2012 . 22667113 .

Notes and References

1. The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis . Gardiner DM, Waring P, Howlett BJ . Microbiology . April 2005 . 151 . 4 . 1021–1032 . 10.1099/mic.0.27847-0 . 15817772. free .
2. Son BW, Jensen PR, Kauffman CA, Fenical W . New cytotoxic epidithiodioxopiperazines related to verticillin A from a marine isolate of the fungus Penicillium . Natural Product Letters . 13 . 3 . 213–222 . May 1999 . 10.1080/10575639908048788 .
3. Figueroa M, Graf TN, Ayers S, Adcock AF, Kroll DJ, Yang J, Swanson SM, Munoz-Acuna U, de Blanco EJ, Agrawal R, Wani MC . Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae . The Journal of Antibiotics . 65 . 11 . 559–564 . November 2012 . 22968289. 10.1038/ja.2012.69 . 3573876.
4. 2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products . Borthwick AD . Chemical Reviews . May 2012 . 112 . 7 . 3641–3716 . 10.1021/cr200398y . 22575049.
5. Boyer N, Morrison KC, Kim J, Hergenrother PJ, Movassaghi M . Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids . Chemical Science . 4 . 4 . 1646–1657 . 2013 . 23914293 . 10.1039/C3SC50174D . 3728915.
6. Kim J, Ashenhurst JA, Movassaghi M . Total synthesis of (+)-11,11'-dideoxyverticillin A . Science . 324 . 5924 . 238–241 . April 2009 . 19359584 . 10.1126/science.1170777 . 4238916.