13-Oxobaccatins, readily available from the naturally abundant 10-deacetyl-baccatin III (10-DAB III), provide an entry for the derivatization of the 14 position of taxanes through the chem. of their enolates. For instance, we have recently reported that the crucial step of hydroxylation of the enolates served for the semi-synthesis of Ortataxel: the lead compd. of a family of potent antitumor taxoids originally obtained from the natural, but scarcely available, 14.beta.-OH-10-deacetyl baccatin III. This preliminary result prompted us to further develop the enolate chem. for building a library of 14.beta.-amino derivs., opening new perspectives in SAR studies of taxanes. Among the wide spectrum of reagents for direct 14.beta.-stereoselective amination of the enolates, tosyl azide gave the best results. This allowed the synthesis of 14.beta.-azido baccatin III (1), key reagent for taxanes with amino based functional groups at the 1,14-position, such as 14.beta.-azido (2),14.beta.-amino (3), 1,14.beta.-carbamate (4), N-BOC-1,14.beta.-carbamate (5), and 1,14.beta.-thiocarbamate (6).

Stereoselective synthesis of 14.beta.-amino taxanes / A. Battaglia, E. Baldelli, E. Bombardelli, G. Carenzi, M.L. Gelmi, A. Guerrini, G. Fontana. - In: ABSTRACTS OF PAPERS - AMERICAN CHEMICAL SOCIETY. - ISSN 0065-7727. - 228:(2004), pp. ORGN-052-ORGN-052. ((Intervento presentato al 228. convegno ACS National Meeting tenutosi a Philadelphia nel 2004.

Stereoselective synthesis of 14.beta.-amino taxanes

M.L. Gelmi;
2004

Abstract

13-Oxobaccatins, readily available from the naturally abundant 10-deacetyl-baccatin III (10-DAB III), provide an entry for the derivatization of the 14 position of taxanes through the chem. of their enolates. For instance, we have recently reported that the crucial step of hydroxylation of the enolates served for the semi-synthesis of Ortataxel: the lead compd. of a family of potent antitumor taxoids originally obtained from the natural, but scarcely available, 14.beta.-OH-10-deacetyl baccatin III. This preliminary result prompted us to further develop the enolate chem. for building a library of 14.beta.-amino derivs., opening new perspectives in SAR studies of taxanes. Among the wide spectrum of reagents for direct 14.beta.-stereoselective amination of the enolates, tosyl azide gave the best results. This allowed the synthesis of 14.beta.-azido baccatin III (1), key reagent for taxanes with amino based functional groups at the 1,14-position, such as 14.beta.-azido (2),14.beta.-amino (3), 1,14.beta.-carbamate (4), N-BOC-1,14.beta.-carbamate (5), and 1,14.beta.-thiocarbamate (6).
Settore CHIM/06 - Chimica Organica
http://oasys2.confex.com/acs/228nm/techprogram/
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/145388
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