@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.}
}
