Semisynthesis of new D-seco-C-nor-taxane derivatives containing a polyfunctionalized furanosyl or cyclopentenyl or cyclopentyl C-ring.

The synthesis of new D-seco-C-nor-taxane derivatives in which the D-ring has been deleted and the C-ring has been transformed into a new pentatomic ring, i.e., the polyfunctionalized tetrahydrofuranosyl and cyclopentenyl or cyclopentyl ring, was performed starting from baccatin III derivatives. The synthetic strategy adopted took advantage of the oxetane ring opening and disconnection of the C4-C5 bond, followed by an intramolecular condensation. The formation of furanosyl or cyclopentyl rings is strictly dependent on the presence of unprotected or protected oxygen at C-7 in the starting material. The reactions proceeded with good diastereoselectivity with control of the stereochemistry of one or two stereocenters.

Synthesis of deserpidine from reserpine.

The Rauwolfia alkaloids reserpine (1) and deserpidine (2), two alkaloids from Rauwolfia species, have been widely used for their antihypertensive action. Deserpidine (2) is a compound with limited availability from natural sources, and its synthesis from 1 in six steps (41% overall yield) is reported here.

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.

Diastereoselective 14beta-hydroxylation of baccatin III derivatives.

14beta-Hydroxybaccatin III, a compound with limited availability by natural sources, is the starting material for the synthesis of the second-generation anticancer taxoid ortataxel. The 7-tert-butoxycarbonyl (1a) and 7-triethylsilyl (1b) derivatives of 14beta-hydroxybaccatin III 1,14-carbonate were synthesized from 10-deacetylbaccatin III (3). The crucial steps were (a) the C(14)beta hydroxylation of the corresponding 13-oxobaccatin III derivatives by oxaziridine-mediated electrophilic oxidation and (b) the reduction of the C(13) carbonyl group with sodium or alkylammonium borohydrides. This protocol provides a practical way for the semisynthesis of ortataxel from 10-deacetylbaccatin III, a compound readily available from various yews.