Cyclotrimerization approach to unnatural structural modifications of pancratistatin and other amaryllidaceae constituents – Synthesis and biological evaluation

Hudlicky, Tomas; Moser, Michael; Banfield, Scott C.; Rinner, Uwe; Chapuis, Jean-Charles; Pettit, George R.
October 2006
Canadian Journal of Chemistry;Oct2006, Vol. 84 Issue 10, p1313
Academic Journal
The phenanthridone core of pancratistatin lacking all aromatic oxygenation was prepared by cyclotrimerization of acetylene-containing scaffolds 30 and 41, reflecting the natural and the C-1 epi configuration, respectively, of the amino inositol moiety. The cobalt-catalyzed formation of the aromatic core led to bisTMS derivatives 39 and 48, as well as bisacetyl derivative 51. The effectiveness of cyclotrimerization of the natural or trans series was compared with that of the cis series. In addition, the yields of cyclotrimerization were compared for propargylic amines and propargylic amides. Eleven derivatives, including the fully hydroxylated phenantridone 39, were tested against seven cancer cell lines. Three of the compounds displayed activities only an order of magnitude less than those of 7-deoxypancratistatin. Full experimental and spectral details are provided for all key compounds and future projections for the preparation of unnatural analogs of Amaryllidaceae constituents are advanced, along with some new insight into the minimum pharmacophore of pancratistatin.


Related Articles

  • Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids. Cedrón, Juan C.; Ravelo, Ángel G.; León, Leticia G.; Padrón, José M.; Estévez-Braun, Ana // Molecules;Aug2015, Vol. 20 Issue 8, p13854 

    The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6)...

  • Two New Tryptamine Derivatives, Leptoclinidamide and (-)-Leptoclinidamine B, from an Indonesian Ascidian Leptoclinides dubius. Yamazaki, Hiroyuki; Wewengkang, Defny S.; Nishikawa, Teruaki; Rotinsulu, Henki; Mangindaan, Remy E. P.; Namikoshi, Michio // Marine Drugs;Jun2012, Vol. 10 Issue 6, p349 

    Two new tryptamine-derived alkaloids, named as leptoclinidamide (1) and (-)-leptoclinidamine B (2), were isolated from an Indonesian ascidian Leptoclinides dubius together with C2-α-D-mannosylpyranosyl-L-tryptophan (3). The structure of 1 was assigned on the basis of spectroscopic data for 1...

  • Synthesis and Antiproliferative Activity of 2,5-bis(3'-Indolyl) pyrroles, Analogues of the Marine Alkaloid Nortopsentin. Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert // Marine Drugs;Mar2013, Vol. 11 Issue 3, p643 

    2,5-bis(3'-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50...

  • Unexpected Formation of Indenoisoquinoline Derivatives from Thia Analogues of Protoberberine Alkaloids. Fodor, Lajos; Csomós, Péter; Molnár, Judit; Zupkó, István; Csámpai, Antal; Sohár, Pál // Letters in Organic Chemistry;Sep2011, Vol. 8 Issue 7, p450 

    Treatment of thia analogues of protoberberine alkaloids, 13-carboxy-13,13a-dihydro-6H,8H-isoquinolino [2,3-c][1,3]benzothiazin-8-ones, with thionyl chloride, followed by ethanol, unexpectedly provided 5,11-dioxoindeno [1,2-c]isoquinoline derivatives containing a novel ring system. Elucidation of...

  • A new flavonol from the stem-bark of Premna fulva. Guang-ying Chen; Chun-yan Dai; Tian-shan Wang; Cai-wu Jiang; Chang-ri Han; Xiao-ping Song // ARKIVOC: Online Journal of Organic Chemistry;2010, p179 

    A new flavonol, 4'-hydroxy-8,3'- dimethoxy-6-acroleinylflavan-3,4-diol (1) has been isolated from the ethyl acetate extract of stem-bark of Premna fulva Craib, together with six known compounds, vanillic acid(2), syringaresinol(3), naringenin(4), p-hydroxybenzoic acid (5), apigenin (6) and...

  • Novel Lycorine Derivatives as Anticancer Agents: Synthesis and In Vitro Biological Evaluation. Peng Wang; Hui-Hui Yuan; Xue Zhang; Yun-Ping Li; Lu-Qing Shang; Zheng Yin // Molecules;Feb2014, Vol. 19 Issue 2, p2469 

    Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae family of plants, reportedly exhibits promising anticancer activities. Herein, a series of novel lycorine derivatives were synthesized and evaluated for their in vitro inhibitory activities against seven different...

  • Protective Effects of Alkaloid Compounds from Nelumbinis Plumula on tert-Butyl Hydroperoxide-Induced Oxidative Stress. Yong Xie; Yi Zhang; Long-Tao Zhang; Shao-Xiao Zeng; Ze-Bin Guo; Bao-Dong Zheng // Molecules;Sep2013, Vol. 18 Issue 9, p10285 

    This study was conducted to investigate the effect of Nelumbinis Plumula total alkaloid (NPA) and its main alkaloid components on oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in the human hepatocellular HepG2 cell line. According to HPLC analysis, several major alkaloid compounds...

  • Population Pharmacokinetic-Pharmacodynamic Analysis of Neutropenia in Cancer Patients Receiving PM00104 (Zalypsis®). Gonzàlez-Sales, Mario; Valenzuela, Bélen; Pérez-Ruixo, Carlos; Fernández Teruel, Carlos; Miguel-Lillo, Bernardo; Soto-Matos, Arturo; Pérez-Ruixo, Juan Jose // Clinical Pharmacokinetics;2012, Vol. 51 Issue 11, p751 

    Background and Objective PM00104 (Zalypsis ®) is a novel marine-derived compound that has shown antineoplastic activity against a number of human tumour cell lines. Myelosuppression was found to be a PM00104 doselimiting toxicity during phase I studies. The objective of this study was to...

  • Novel Antitumor Agents: Marine Sponge Alkaloids, their Synthetic Analogs and Derivatives. Dembitsky, Valery M.; Gloriozova, Tatyana A.; Poroikov, Vladimir V. // Mini Reviews in Medicinal Chemistry;Mar2005, Vol. 5 Issue 3, p319 

    Present review describes research on novel natural antitumor agents isolated from marine sponges. More than 90 novel cytotoxic antitumor compounds and their synthetic analogs have shown confirmed activity in vitro tumor cell lines bioassay and are of current interest to NCI for further in vivo...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics