A pinacol rearrangement/oxidation synthetic route to hydroxyphenstatin.
In an attempt to develop biologically active compounds from the inactive trans isomer (3a) of stilbene 1a, after asymmetric dihydroxylation to optically pure (R,R)-diol 8 the unexpected racemic diphenylacetaldehyde (9) was generated via a Pinacol rearrangement. Several derivatives of diphenylacetaldehyde 9 were synthesized (11-15) and reported. Further reaction of aldehyde 9 during desilylation through autoxidative decarbonylation afforded benzophenone 2b, designated hydroxyphenstatin, a potent antitumor and antimitotic agent. Hydroxyphenstatin showed potent inhibition of the tubulin assembly (IC(50) 0.82 microM) and exhibited an ED(50) of 2.5 microg/mL against the P388 lymphocytic leukemia cell line.
Pettit
G R
GR
Cancer Research Institute and Department of Chemistry, Arizona State University, Tempe, Arizona 87287-2404, USA.
Lippert
J W
JW
Herald
D L
DL
D000349:Africa; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001577:Benzophenones / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010946:Plants, Medicinal / Q000737:chemistry
D000970:Antineoplastic Agents; D001577:Benzophenones; D007202:Indicators and Reagents; C411463:hydroxyphenstatin