Antineoplastic agents. 565. Synthesis of combretastatin D-2 phosphate and dihydro-combretastatin D-2.
A modified synthetic route to combretastatin D-2 (5) was devised in order to further evaluate its biological activity, for its conversion to phosphate prodrugs (25-28), and as a route to obtaining dihydro-combretastatin D-2 (42). A parallel first total synthesis of dihydro-combretastatin D-2 was completed, proceeding from a saturated 3-phenylpropionic ester intermediate via the Ullmann biaryl ether reaction (39-41). In contrast to the cancer cell growth inhibitory activity exhibited by combretastatin D-2, relatively minor structural modifications (41, 42) caused elimination of those properties.
Pettit
George R
GR
Department of Chemistry and Biochemistry, Cancer Research Institute, Arizona State University, PO Box 871604, Tempe, Arizona 85287-1604, USA. bpettit@asu.edu
Quistorf
Peter D
PD
Fry
Jeremy A
JA
Herald
Delbert L
DL
Hamel
Ernest
E
Chapuis
Jean-Charles
JC
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001632:Bibenzyls / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D007783:Lactones; D010647:Phenyl Ethers; D011355:Prodrugs; C521610:combretastatin D2; C040105:combretastatin