(+)-Phorboxazole A synthetic studies. Identification of a series of highly cytotoxic C(45-46) analogues.
[structure: see text] Effective, scalable total syntheses and biological evaluation of six phorboxazole A analogues (1-6) have been achieved. Importantly, the C(45-46)-saturated, C(45-46)-alkenyl, and the C(45-46)-E-chloroalkenyl congeners (4, 5, and 6, respectively) reveal low nanomolar tumor cell growth inhibitory activity (GI50's) similar to or, in some cell lines, greater than that of the phorboxazoles across a diverse panel of human cancer cell lines.
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Razler
Thomas M
TM
Pettit
George R
GR
Chapuis
Jean-Charles
JC
D002244:Carbon / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship
D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408887:phorboxazole A; D002244:Carbon