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.
Baldelli
Eleonora
E
Istituto CNR per la Sintesi Organica e Fotoreattività I.S.O.F., Area della Ricerca di Bologna, Via P. Gobetti 101, 40129 Bologna, Italy.
Battaglia
Arturo
A
Bombardelli
Ezio
E
Carenzi
Giacomo
G
Fontana
Gabriele
G
Gambini
Andrea
A
Gelmi
Maria Luisa
ML
Guerrini
Andrea
A
Pocar
Donato
D
D000470:Alkaloids / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis; D000077143:Docetaxel; D006900:Hydroxylation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000031:analogs & derivatives; D013237:Stereoisomerism; D043823:Taxoids / Q000737:chemistry*
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; C073950:baccatin III; C042213:10-deacetylbaccatine III; D017239:Paclitaxel