Dideoxyverticillin A

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
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-[10b,10′b-bi-3,11a-disulfanopyrazino[1′,2′:1,5]pyrrolo[2,3-b]indole]-1,1′,4,4′-tetrone
Other names
11,11′-Dideoxyverticillin A; 11,11′-Dideoxyverticillin
Identifiers
ChEMBL
ChemSpider
UNII
Properties
C30H28N6O4S4
Molar mass 664.83 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

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.[4] 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]

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.
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