252981-50-3Relevant academic research and scientific papers
Total Synthesis and Antitumor Activity of 12,13-Desoxyepothilone F: An Unexpected Solvolysis Problem at C15, Mediated by Remote Substitution at C21
Lee, Chul Bom,Chou, Ting-Chao,Zhang, Xiu-Guo,Wang, Zhi-Guang,Kuduk, Scott D.,Chappell, Mark D.,Stachel, Shawn J.,Danishefsky, Samuel J.
, p. 6525 - 6533 (2000)
A new epothilone analogue, 12,13-desoxyepothilone F (dEpoF, 21-hydroxy-12,13-desoxyepothilone B, 21-hydroxyepothilone D), was synthesized and evaluated for antitumor potential. A convergent strategy employed for the semipractical synthesis of 12,13-desoxyepothilone B (dEpoB) has been utilized to yield an amount of dEpoF sufficient for relevant biological studies. The results from an in vitro assay reveal that this new analogue is highly active against various tumor cell lines with a potency comparable to that of dEpoB. In particular, the growth of resistant tumor cells is inhibited by dEpoF at concentrations where paclitaxel (Taxol) is basically ineffective. A preliminary assessment of its in vivo activity is also promising. The new analogue, containing an additional hydroxyl group at C21, exhibits advantages over other epothilones in terms of water solubility, and can serve as a readily functionalizable handle to produce other useful compounds for pertinent biological studies.
METHODS, KITS, AND COMPOUNDS FOR DETERMINING RESPONSIVENESS TO TREATMENT OF A PATHOLOGICAL DISORDER BY EPOTHILONES
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, (2009/04/24)
The invention provides methods, kits and compounds for determining the potential responsiveness of a subject suffering from a pathological disorder, including non-small cell lung cancer (NSCLC), to treatment with an epothilone by analyzing the gene expression profile and/or certain molecular markers in a sample obtained from said subject. The invention further relates to methods, compounds and uses of said compounds for treating subjects suffering from said pathologic disorder, optionally in combination with other therapeutic agents. Also provided are genes and/or proteins encoded by them whose expression level have been determined to differ between epothilone responders and epothilone non-responders.
Catalytic antibody route to the naturally occurring epothilones: Total synthesis of epothilones A-F
Sinha, Subhash C.
, p. 1691 - 1702 (2007/10/03)
Naturally occurring epothilones have been synthesized starting from enantiomerically pure aldol compounds 9-11, which were obtained by antibody catalysis. Aldolase antibody 38C2 catalyzed the resolution of (±)-9 by enantioselective retro-aldol reaction to afford 9 in 90% ee at 50% conversion. Compounds 10 and 11 were obtained in more than 99% ee at 50% conversion by resolution of their racemic mixtures using newly developed aldolase antibodies 84G3, 85H6 or 93F3. Compounds 9, 10 and 11 were resolved in multigram quantities and then converted to the epothilones by metathesis processes, which were catalyzed by Grubbs' catalysts.
Insights into long-range structural effects on the stereochemistry of aldol condensations: A practical total synthesis of desoxyepothilone F
Chul Bom Lee,Wu,Zhang,Chappell,Stachel,Chou,Guan,Danishefsky
, p. 5249 - 5259 (2007/10/03)
A processable total synthesis of a potent antitumor agent, desoxyepothilone F (dEpoF, 21-hydroxy-12,13-desoxyepothilone B, 21-hydroxyepothilone D), has been accomplished. The route is highly convergent. The new technology has also been applied to a total
