Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012;90(11):932-943.
doi: 10.1139/v2012-073. Epub 2012 Sep 19.

Unnatural C-1 homologues of pancratistatin - Synthesis and promising biological activities

Sergey Vshyvenko  1 , Jon Scattolon  1 , Tomas Hudlicky  1 , Anntherese E Romero  2 , Alexander Kornienko  2 , Dennis Ma  3 , Ian Tuffley  3 , Siyaram Pandey  3
Affiliations

Unnatural C-1 homologues of pancratistatin - Synthesis and promising biological activities

Sergey Vshyvenko et al. Can J Chem. 2012.

Abstract
in English, French

Several C-1 homologues of pancratistatin and 7-deoxypancratistatin were synthesized by a phenanthrene-phenathridone oxidative recyclization strategy. The key steps involved the enzymatic dihydroxylation of bromobenzene, addition of an aryl alane to an epoxyaziridine, an intramolecular aziridine opening on silica gel in solid phase, and the above-mentioned recylization strategy. Experimental and spectral data are reported for all new compounds. All synthesized C-1 homologues of pancratistatin and 7-deoxypancratistatin were evaluated for antiproliferative activity in a panel of human cancer cell lines. As expected, the 7-hydroxy compounds were found to be more potent and the activity of the C-1 benzoxymethyl analogue exceeded that of narciclasine, which was used as a positive control.

On a réalisé la synthèse de plusieurs homologues en C-1 de la pancratistatine et de la 7-désoxypencratistatine en faisant appel à une stratégie de recyclisation oxydante phenantrène–phénathridone. Les étapes clés impliquent la dihydroxylation du bromobenzène, l’addition d’une arylalane à une époxyaziridine, une ouverture intramoléculaire d’aziridine sur gel de silice en phase solide et la stratégie de recyclisation mentionnée plus haut. Les données expérimentales et spectrales sont rapportées pour tous les nouveaux produits. Tous les homologues en C-1 de la pancratistatine et de la 7-désoxypencratistatine ont été évalués pour leur activité à contrer la prolifération dans un éventail de lignées de cellules cancéreuses humaines. Tel que prévu, les composés 7-hydroxy sont les plus puissants alors que l’activité de l’analogue C-1 benzoxyméthyle est supérieure à celle de la narciclasine qui a été utilisée comme contrôle positif.

Keywords: C-1 homologues of pancratistatin; amaryllidaceae alkaloids; anticancer activities; intramolecular aziridine opening; solid-phase silica catalysis.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Pancratistatin, other Amaryllidaceae congeners, and C-1 homologues.
Fig. 2
Fig. 2
Pancratistatin analogues cause cytotoxicity in cancer cells in a dose-dependent manner.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Scheme 3
Scheme 3
Scheme 4
Scheme 4
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Pettit GR, Gaddamidi V, Cragg GM, Herald DL, Sagawa Y. J. Chem. Soc. Chem. Commun. 1984;(24):1693. doi:10.1039/c39840001693.
    1. Kornienko A, Evidente A. Chem. Rev. 2008;108(6):1982. For reviews see. doi:10.1021/cr078198u. - PMC - PubMed
    2. Manpadi M, Kornienko A. Org. Prep. Proced. Int. 2008;40(2):107. doi:10.1080/00304940809458083. - PMC - PubMed
    3. Chapleur Y, Chrétien F, Ahmed SI, Khaldi M. Curr. Org. Synth. 2006;3(3):341. doi:10.2174/157017906777934872.
    4. Rinner U, Hudlicky T. Synlett. 2005:365.
    5. Bridges A. Chemtracts: Organic Chemistry. 1996;9:101.
    1. Collins J, Rinner U, Moser M, Hudlicky T, Ghiviriga I, Romero AE, Kornienko A, Ma D, Griffin C, Pandey S. J.Org. Chem. 2010;75(9):3069. For a recent compilation of total syntheses of Amaryllidaceae constituents see. doi:10.1021/jo1003136. - PMC - PubMed
    2. Yadav JS, Satheesh G, Murthy CVSR. Org. Lett. 2010;12(11):2544. For syntheses published after 2009 see. doi:10.1021/ol100755v. - PubMed
    3. Dam JH, Madsen R. Eur. J. Org. Chem. 2009;2009(27):4666. doi:10.1002/ejoc.200900719.
    1. Pettit GR, Melody N, O'Sullivan M, Thompson MA, Herald DL, Coates B. J.Chem. Soc. Chem. Commun. 1994:2725. doi:10.1039/c39940002725.
    2. Pettit GR, Freeman S, Simpson MJ, Thompson MA, Boyd MR, Williams MD, Pettit GR, III, Doubek DL. Anticancer Drug Des. 1995;10:243. - PubMed
    3. Pettit GR, Melody N, Herald DL. J. Org. Chem. 2001;66(8):2583. doi:10.1021/jo000710n. - PubMed
    4. Pettit GR, Melody N, Herald DL, Knight JC, Chapuis J-C. J. Nat. Prod. 2007;70(3):417. doi:10.1021/np068046e. - PubMed
    5. Pettit GR, Ducki S, Eastham SA, Melody N. J.Nat. Prod. 2009;72(7):1279. doi:10. 1021/np9001948. - PMC - PubMed
    6. Pettit GR, Tan R, Bao G-H, Melody N, Doubek DL, Gao S, Chapuis J-C, Williams L. J.Nat. Prod. 2012;75(4):771. doi:10.1021/np200862y. - PMC - PubMed
    1. McNulty J, Mao J, Gibe R, Mo R, Wolf S, Pettit GR, Herald DL, Boyd MR. Bioorg. Med. Chem. Lett. 2001;11(2):169. doi:10.1016/S0960-894X(00)00614-4. - PubMed
    2. McNulty J, Larichev V, Pandey S. Bioorg. Med. Chem. Lett. 2005;15(23):5315. doi:10.1016/j.bmcl.2005.08.024. - PubMed
    3. McNulty J, Nair JJ, Griffin C, Pandey S. J.Nat. Prod. 2008;71(3):357. doi:10.1021/np0705460. - PubMed
    4. McNulty J, Nair JJ, Little JRL, Brennan JD, Bastida J. Bioorg. Med. Chem. Lett. 2010;20(17):5290. doi:10.1016/j.bmcl.2010.06.130. - PubMed
    5. McNulty J, Nair JJ, Singh M, Crankshaw DJ, Holloway AC. Bioorg. Med. Chem. Lett. 2010;20(7):2335. doi:10.1016/j.bmcl.2010.01.157. - PubMed