Ortataxel, a new taxane deriv. bearing a 1,14-carbonate moiety, exhibits improved clin. properties such as oral bioavailability and a wider spectrum of antitumor activity compared to previously reported taxanes. Recently, our research group has developed a semi-synthetic protocol for the prepn. of 14.beta.-hydroxy-baccatins. The key step was accomplished by oxidizing the enolate of 13-oxo-7-protected-baccatin III. The possibility of quenching the enolate of 13-oxobaccatin with different electrophiles opened the way to the introduction of new functionalities in position 14. Since bioisosters are known in many cases to improve the efficacy of a drug, new promising anticancer agents were designed and developed in our lab. We focused on the synthesis of compds. 1,2 contg. the unsatd. and satd. baccatin[14,1-d]-furan-2-one nucleus, resp.: an aldol condensation provided a carbon atom linked to C-14 instead of the oxygen atom in Ortataxel.

New taxane derivatives: synthesis of baccatin[14-1-d]-furan-2-one core and its condensation with norstatine side chain / G. Carenzi, M.L. Gelmi, A. Battaglia, E. Baldelli, E. Bombardelli, G. Fontana. - In: ABSTRACTS OF PAPERS - AMERICAN CHEMICAL SOCIETY. - ISSN 0065-7727. - 2004:(2004), pp. ORGN-053-ORGN-053. ((Intervento presentato al 228. convegno ACS National Meeting tenutosi a Philadelphia nel 2004.

New taxane derivatives: synthesis of baccatin[14-1-d]-furan-2-one core and its condensation with norstatine side chain

M.L. Gelmi
Secondo
;
2004

Abstract

Ortataxel, a new taxane deriv. bearing a 1,14-carbonate moiety, exhibits improved clin. properties such as oral bioavailability and a wider spectrum of antitumor activity compared to previously reported taxanes. Recently, our research group has developed a semi-synthetic protocol for the prepn. of 14.beta.-hydroxy-baccatins. The key step was accomplished by oxidizing the enolate of 13-oxo-7-protected-baccatin III. The possibility of quenching the enolate of 13-oxobaccatin with different electrophiles opened the way to the introduction of new functionalities in position 14. Since bioisosters are known in many cases to improve the efficacy of a drug, new promising anticancer agents were designed and developed in our lab. We focused on the synthesis of compds. 1,2 contg. the unsatd. and satd. baccatin[14,1-d]-furan-2-one nucleus, resp.: an aldol condensation provided a carbon atom linked to C-14 instead of the oxygen atom in Ortataxel.
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/2434/145469
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