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Dideoxyverticillin A

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Dideoxyverticillin A
Names
Preferred IUPAC name (3S,3′S,5aR,5′aR,10bR,10′bR,11aS,11′aS)-2,2′,3,3′-Tetramethyl-2,2′,3,3′,5a,5′a,6,6′-octahydro-11H,11′H-pyrroloindole]-1,1′,4,4′-tetrone
Other names 11,11′-Dideoxyverticillin A; 11,11′-Dideoxyverticillin
Identifiers
CAS Number
ChEMBL
ChemSpider
PubChem CID
UNII
Properties
Chemical formula C30H28N6O4S4
Molar mass 664.83 g·mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references
Chemical compound

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

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.

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.

References

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

External links

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