Synthesis and evaluation of a novel E-ring modified alpha-hydroxy keto ether analogue of camptothecin.
The synthesis of a novel E-ring modified keto ether analogue of camptothecin and homocamptothecin by the cascade radical annulation route is reported. The analogue, Du1441, is an isomer of homocamptothecin, but includes the alpha-hydroxy carbonyl functionality that camptothecin possesses and homocamptothecin lacks. Despite these similarities, the new keto ether analogue is inactive in cell assays, and implications for the structure/activity relationship are discussed.
Du
Wu
W
University of Pittsburgh, Department of Chemistry, Pittsburgh, PA 15260, USA.
Curran
Dennis P
DP
Bevins
Robert L
RL
Zimmer
Stephen G
SG
Zhang
Junhong
J
Burke
Thomas G
TG
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004987:Ethers / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004987:Ethers; D002166:Camptothecin