An efficient synthesis of the taxane-derived anticancer agent ABT-271.
ABT-271, 1, has been identified as a promising anticancer agent. ABT-271 is a novel taxane possessing a C9-(R)-hydroxyl group as opposed to a C9-ketone which is present in Taxol and Taxotere. To further evaluate ABT-271 as a potential anticancer agent, an efficient synthesis was developed which allows the large scale synthesis of ABT-271. Ketalization of the 7,9-diol of 9-DHAB-III, 2, allows selective removal of the C13-acetate with phenyllithium. The resulting C13-hydroxyl group is then acylated using LiHMDS and beta-lactam 22 to give ABT-271 in protected form. The protecting groups were removed first by acidic hydrolysis followed by basic hydrolysis to provide ABT-271. Application of this synthetic sequence provided over 600 g of ABT-271, 1.
DeMattei
J A
JA
Process Research, Pharmaceutical Products Division, Abbott Laboratories, North Chicago, Illinois 60064-4000, USA. jdemattei@arraybiopharma.con
Leanna
M R
MR
Li
W
W
Nichols
P J
PJ
Rasmussen
M W
MW
Morton
H E
HE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D003460:Crystallization; D008968:Molecular Conformation; D043823:Taxoids
C442359:ABT-271; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane