Owing to the tighter binding of the coumarin moiety to the PTP active site compared to phosphotyrosine as determined by lower Km values for coumarin substrates, we envisioned the use of coumarin based inhibitors for PTPs. Similar to pmp and F2pmp, two inhibitors were designed and synthesized.
In the synthesis of the coumarin mold metabolite aflatoxin Buchi and Weinreb found that the usual conditions could not be employed because the phenol is exceptionally sensitive to acidic reagents.
Synthesis of Coumarin by Perkin ReactionBack to Top
When aromatic aldehyde is heated with the anhydride of an aliphatic acid in the presence of the sodium salt of the same acid, an $\alpha$, $\beta$-unsaturated acid is formed. This reaction is termed as perkins reaction.
An important extension of perkins reaction is in the synthesis of coumarin, which is used in perfumery.
Coumarin derivatives are important chemicals in the perfume, cosmetic, agricultural and pharmaceutical industries.
Pechmann Coumarin SynthesisBack to Top
One of the most extended procedures for coumarin synthesis consists of a Pechmann condensation, an acid catalyzed condensation of phenol with a $\beta$-ketoester. The reaction mechanism is initiated by an electrophilic aromatic substitution and involves a final step of localization. Lewis acid-mediated condensation of phenol with $\beta$-ketoester is known as Pechmann coumarin synthesis.
Among the different reaction conditions this describes a coumarin synthesis in the absence of solvent through a Pechmann condensation catalyzed by titanium tetrachloride.
Synthesis of Coumarin DerivativesBack to Top
Coumarin and its derivatives find their main application as fragrances, pharmaceuticals and Agrochemicals. Numerous synthetic routes to the coumarins have been described including the Pechmann, Perkin, knovenagal, Reformatsky and Wittig reactions.
The synthesis of coumarin derivatives that are unsubstituted at position 4. Reactions catalyzed by solid acid catalysts using microwave irradiation or classical methods.
The result of a comparative study on the synthesis of coumarins involving classical heating in conjunction with solid acid catalysts, both with or without solvent, and microwave irradiation are shown in the above table.