@article {2549,
	title = {Synthetic Approaches to the Microtubule-Stabilizing Sponge Alkaloid Ceratamine A and Desbromo Analogues},
	journal = {Journal of Organic Chemistry},
	volume = {74},
	number = {3},
	year = {2009},
	note = {ISI Document Delivery No.: 402HHTimes Cited: 6Cited Reference Count: 58Nodwell, Matt Pereira, Alban Riffell, Jenna L. Zimmerman, Carla Patrick, Brian O. Roberge, Michel Andersen, Raymond J.},
	month = {Feb},
	pages = {995-1006},
	type = {Article},
	abstract = {Two synthetic approaches to the microtubule-stabilizing ceratamine alkaloids are described. The first approach involved attempts to graft an aminoimidazole moiety onto an azepine ring to form partially hydrogenated versions of the unprecedented aromatic imidazo[4,5-d]azepine core of the ceratamines. This route ultimately failed because it was not possible to aromatize the partially hydrogenated ceratamine intermediates. A second approach started with tribromoimidazole that was sequentially metalated and functionalized to efficiently generate a key imidazole intermediate containing vinyl bromide and amide functionalities. An intramolecular Buchwald vinyl amidation reaction converted this key intermediate into a bicyclic imidazol[4,5-d]azepine that was at the same oxidation state as the aromatic core of the ceratamines. The 2-amino functionality present on the imidazole ring of the ceratamines was installed using a Buchwald/Hartwig amination reaction on a 2-chloroimidazole precursor. Deprotection and aromatization resulted in the first synthesis of desbromoceratamine A (55) and desmethyldesbromoceratamine A (60). An unanticipated addition of atmospheric oxygen was encountered during deprotection of the imidazole ring in the last step of the synthesis leading to C-11 oxygenated ceratamine analogues as byproducts. Evaluation of the synthetic ceratamines in a TG3 cell-based assay for mitotic arrest revealed that the C-14 and C-16 bromine substituents in ceratamine A (1) play a major role in the antimitotic potency of the natural product. The synthetic route to ceratamine analogues has provided sufficient quantities of desbromoceratamine A (55) for testing in mouse models of cancer.},
	keywords = {6-PI-2-AZATRIENE ELECTROCYCLIZATION, AGELADINE-A, ANTIMITOTIC AGENTS, ARYL CHLORIDES, DIRECTED LITHIATION, HALIDES, IMIDAZOLE, PACLITAXEL, PALLADIUM-CATALYZED AMINATION, TAXOL},
	isbn = {0022-3263},
	url = {<Go to ISI>://000263004300005},
	author = {Nodwell, M. and Pereira, A. and Riffell, J. L. and Zimmerman, C. and Patrick, B. O. and Roberge, M. and Andersen, R. J.}
}
@article {5024,
	title = {Synthetic transformations of eleutherobin reveal new features of its microtubule-stabilizing pharmacophore},
	journal = {Journal of the American Chemical Society},
	volume = {123},
	number = {35},
	year = {2001},
	note = {ISI Document Delivery No.: 467XNTimes Cited: 21Cited Reference Count: 13},
	month = {Sep},
	pages = {8632-8633},
	type = {Article},
	keywords = {AGENTS, COMMON PHARMACOPHORE, PACLITAXEL, TAXOL, TUBULIN},
	isbn = {0002-7863},
	url = {<Go to ISI>://000170729200037},
	author = {Britton, R. and De Silva, E. D. and Bigg, C. M. and McHardy, L. M. and Roberge, M. and Andersen, R. J.}
}
@article {4775,
	title = {Antimitotic diterpenes from Erythropodium caribaeorum test pharmacophore models for microtubule stabilization},
	journal = {Organic Letters},
	volume = {2},
	number = {3},
	year = {2000},
	note = {ISI Document Delivery No.: 282UXTimes Cited: 36Cited Reference Count: 17},
	month = {Feb},
	pages = {257-260},
	type = {Article},
	abstract = {[GRAPHICS] Six new antimitotic diterpenes, 2-7, have been isolated from the Caribbean octocoral Erythropodium caribaeorum, Structural variations encountered in this group of natural products test recently proposed pharmacophore models for microtubule stabilizing compounds.},
	keywords = {AGENTS, ELEUTHEROBIN, TAXOL, TUBULIN},
	isbn = {1523-7060},
	url = {<Go to ISI>://000085238900007},
	author = {Cinel, B. and Roberge, M. and Behrisch, H. and van Ofwegen, L. P. and Castro, C. B. and Andersen, R. J.}
}
@article {4916,
	title = {Cell-based screen for antimitotic agents and identification of analogues of rhizoxin, eleutherobin, and paclitaxel in natural extracts},
	journal = {Cancer Research},
	volume = {60},
	number = {18},
	year = {2000},
	note = {ISI Document Delivery No.: 358GQTimes Cited: 62Cited Reference Count: 55},
	month = {Sep},
	pages = {5052-5058},
	type = {Article},
	abstract = {We describe a cell-based assay for antimitotic compounds that is suitable for drug discovery and for quantitative determination of antimitotic activity, In the assay, cells arrested in mitosis as a result of exposure to antimitotic agents in pure form or in crude natural extracts are detected by ELISA using the monoclonal antibody TG-3, The assay was used to screen >24,000 extracts of marine microorganisms and invertebrates and terrestrial plants and to guide the purification of active compounds from 5 of 119 positive extracts. A new rhizoxin analogue was found in a Pseudomonas species, six new eleutherobin analogues were identified from the octocoral Erythropodium caribaeorum, and two paclitaxel analogues were found in the stem bark of the tree Ilex macrophylla. The assay was also used for quantitative comparison of the antimitotic activity of different analogues. It revealed the importance of the C-11 to C-13 segment of the diterpene core of eleutherobin for its antimitotic activity. The identification of antimitotic compounds in very low abundance and their high (0.5\%) occurrence in natural extracts indicates that drug discovery efforts using this cell-based assay may lead to the identification of structurally novel antimitotic agents.},
	keywords = {AGENT, ANTITUMOR, BINDING, fungus, INHIBITION, MACROCYCLIC LACTONE ANTIBIOTICS, MICROTUBULE-STABILIZING AGENTS, MITOTIC SPINDLES, RHIZOPUS-CHINENSIS, TAXOL, TUBULIN POLYMERIZATION},
	isbn = {0008-5472},
	url = {<Go to ISI>://000089550600013},
	author = {Roberge, M. and Cinel, B. and Anderson, H. J. and Lim, L. and Jiang, X. X. and Xu, L. and Bigg, C. M. and Kelly, M. T. and Andersen, R. J.}
}
@article {4774,
	title = {Solid-state and solution conformations of eleutherobin obtained from X-ray diffraction analysis and solution NOE data},
	journal = {Tetrahedron Letters},
	volume = {41},
	number = {16},
	year = {2000},
	note = {ISI Document Delivery No.: 307YFTimes Cited: 2Cited Reference Count: 13},
	month = {Apr},
	pages = {2811-2815},
	type = {Article},
	abstract = {Single crystal X-ray diffraction analysis has revealed the solid-state conformation of the microtubule-stabilizing diterpenoid eleutherobin (1). NOE data obtained for 1 in CDCl3 and DMSO-d(6) are consistent with solution conformations that are virtually identical to the solid state conformation. (C) 2000 Elsevier Science Ltd. All rights reserved.},
	keywords = {MICROTUBULE-STABILIZING AGENTS, PACLITAXEL, TAXOL},
	isbn = {0040-4039},
	url = {<Go to ISI>://000086681200012},
	author = {Cinel, B. and Patrick, B. O. and Roberge, M. and Andersen, R. J.}
}
@article {4434,
	title = {Ambewelamides A and B, antineoplastic epidithiapiperazinediones isolated from the lichen Usnea sp},
	journal = {Tetrahedron Letters},
	volume = {39},
	number = {52},
	year = {1998},
	note = {ISI Document Delivery No.: 148LLTimes Cited: 19Cited Reference Count: 15},
	month = {Dec},
	pages = {9579-9582},
	type = {Article},
	abstract = {Two potently cytotoxic epidithiapiperazinediones, ambewelamides A (1) and B (2), have been isolated from the lichen Usnea sp. collected in Sri Lanka. The structures were determined by a combination of X-ray crystallographic and spectroscopic analyses. (C) 1998 Elsevier Science Ltd. All rights reserved.},
	keywords = {microtubules, TAXOL},
	isbn = {0040-4039},
	url = {<Go to ISI>://000077506700001},
	author = {Williams, D. E. and Bombuwala, K. and Lobkovsky, E. and De Silva, E. D. and Karunaratne, V. and Allen, T. M. and Clardy, J. and Andersen, R. J.}
}
@article {3876,
	title = {Cytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic arrest and abnormal spindle formation},
	journal = {Cancer Chemotherapy and Pharmacology},
	volume = {39},
	number = {3},
	year = {1997},
	note = {ISI Document Delivery No.: VZ251Times Cited: 66Cited Reference Count: 17},
	month = {Jan},
	pages = {223-226},
	type = {Article},
	abstract = {Purpose: Hemiasterlin, hemiasterlin A and hemiasterlin B are newly isolated cytotoxic tripeptides with potential as antitumor drugs. We wished to determine their mechanism of cytotoxicity. Methods: We studied their effect on cell survival, cell cycle progression, and microtubule morphology in MCF-7 human mammary carcinoma cells. Results: At the nanomolar concentrations at which they were cytotoxic, the peptides induced arrest in mitotic metaphase. Hemiasterlin A produced abnormal mitotic spindles like those produced by the microtubule inhibitors taxol, nocodazole and vinblastine at low concentrations. At high concentrations hemiasterlin A did not cause microtubule bundling like taxol, but caused microtubule depolymerization like nocodazole and vinblastine. Conclusions: The hemiasterlins probably exert their cytotoxic effect by inhibiting spindle microtubule dynamics.},
	keywords = {CANCER, COLCHICINE SITE, FOSTRIECIN, INHIBITION, microtubules, mitosis, NATURAL-PRODUCTS, OKADAIC ACID, PHOSPHATASE-2A, PODOPHYLLOTOXIN, TAXOL, TUBULIN, VINBLASTINE, VINCA DOMAIN},
	isbn = {0344-5704},
	url = {<Go to ISI>://A1997VZ25100008},
	author = {Anderson, H. J. and Coleman, J. E. and Andersen, R. J. and Roberge, M.}
}
