New taxane derivatives: synthesis of baccatin[14,1-d]furan-2-one nucleus and its condensation with the norstatine side chain.
New taxanes 15 and 18, containing the unsaturated and saturated baccatin[14,1-d]furan-2-one nucleus, respectively, were prepared starting from the readily available 13-oxo-7-Tes-baccatin III (3). Sequential formation of the enolate of 3 and reaction with ethyl glyoxylate gave the 13-oxo-7-Tes-baccatin[14,1-d]-3,4-dehydrofuran-2-one 4. The reduction of 4 can result in the formation of a mixture of compounds corresponding to 13-hydroxy alcohol 5 and 13-enol derivative 6. Both 5 and 6 were transformed into 13-oxo-7-Tes-baccatin[14,1-d]furan-2-one 8 by treatment with a base. Further reduction of 8 gave 13-hydroxy compound 9. Esterification of 6 and 9 with N,O-protected norstatine 12, followed by deprotection, gave the new promising anticancer taxanes 15 and 18, respectively.
Baldelli
Eleonora
E
Istituto CNR per la Sintesi Organica e Fotoreattività "ISOF", Area della Ricerca di Bologna, Italy.
Battaglia
Arturo
A
Bombardelli
Ezio
E
Carenzi
Giacomo
G
Fontana
Gabriele
G
Gelmi
Maria Luisa
ML
Guerrini
Andrea
A
Pocar
Donato
D
D000970:Antineoplastic Agents / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry
D000970:Antineoplastic Agents; D043823:Taxoids