Identification of Novel and Improved Antimitotic Agents Derived from Noscapine

Abstract

Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold more potent than noscapine in reducing cell proliferation in rapidly dividing cells.

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…[193] They found that in order to avoid epimerization of the phthalide center it was essential to employ a weak base. They explored the use of K 2 CO 3 , Cs 2 CO 3 and KOH but these were all reported to give poor conversion.…”

Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents

“…The 7-OTf was also converted to the 7-thiophenol (7-SH) analog (structure undisclosed) which, interestingly enough, shared similar activity to 19, arresting HEK293 cells in G 2 /M. 118 The activity was presumed to be due to the presence of hydrogen bond donors at the 7-position, but this was refuted when conversion of the 7-OTf analog to the 7-H analog (structure undisclosed) also 119 It has been reported that carbamate esters are able to mask free phenolic groups in cytotoxic compounds. 120 The regioselective O-demethylation at the 7-position to give 17 which was ~100-fold more potent than 6, indicating the chemical modification around the phthalide ring has a significant impact on the biological activity of 6.…”

Biarylphosphanliganden in der palladiumkatalysierten Aminierung

“…[193] Sie fanden heraus, dass eine schwache Base eingesetzt werden musste, um die Epimerisierung des Phthalidzentrums zu vermeiden. K 2 CO 3 , Cs 2 CO 3 und KOH ergaben nur schlechte Umsätze, ebenso die Ammoniak-¾quivalente Benzophenonimin, LiHMDS und tert-Butylcarbamat.…”