Chemoselective Synthesis of Enamino‐Coumarin Derivatives Identified as Potent Antitumor Agents

Abstract

The reaction of 4‐aminocoumarin (2) with benzaldehyde gave the bisenamino derivatives 4. Thus, transamination of 2 with o‐phenylenediamine furnished enamino skeleton 3, which can be obtained from 1. Reaction of 1 with 5‐aminoisoxazole afforded 5. While reaction of 2 with benzalaniline, isatinanil and phenyl isothio cyanate afforded the corresponding 7, 8 and 9, respectively. Heterocyclic annulations of 2‐phenylthiazolidine‐4‐one 10 2‐phenylthiazolidin‐4‐one 10 and 2‐phenyl‐thiazinan‐4‐one 11 systems were achieved via reaction of 2 with benzaldehyde and rather either 2‐mercaptoacetic acid or 3‐mercaptopropanoic acid respectively. The behavior of 2 towards monochloro acetic acid and 4‐oxo‐4‐phenylbuatonic 4‐Oxo‐4‐phenylbutanoic acid was investigated. All of the newly synthesized compounds were evaluated as antitumor (cytotoxic) agents. Most of these compounds have shown significant antitumor activities.

Chemistry of 1,3-thiazin-4-ones and their derivatives, 1995 - mid-2018

“…120,128 T3P 159 has been shown to work with N-acetylcysteine as the thioacid. 93,117,133 Acid catalysis has also been used. Acids used include ZnCl 2 134 and TsOH.…”

An Overview of the Synthesis of 3,4-Fused Pyrrolocoumarins of Biological Interest

“…Ibrahim et al reported that the reaction of 4-aminocoumarin (5) with chloroacetic acid resulted in 1,2-dihydrochromeno [4,3-b]pyrrole-3,4-dione (22) in 58% yield (Scheme 7). This compound was studied for cytotoxic activity and found to be 1.5-fold more toxic than the standard 5-fluorouracil [75].…”