Silvia Tagliapietra

An asymmetric approach to coumarin anticoagulants via hetero-Diels–Alder cycloaddition

Abstract We have developed a general, two-step protocol for the synthesis of chiral non-racemic coumarin anticoagulants (e.g. warfarin, coumachlor and acenocoumarol). This approach features a one-pot three-component tandem Knoevenagel–hetero-Diels–Alder reaction between in situ generated 3-arylidene-2,4-chromanediones and iso -propenyl ether derived from (−)-menthol.

Ferprenin, a prenylated coumarin from Ferula communis

Abstract The structure of ferprenin, a prenylated coumarin from Ferula communis, has been established from spectral data, and by synthesis from E,E-farnesal and 4-hydroxycoumarin. Ferprenin could also be obtained from ferulenol, the major constituent of the plant investigated, by a Cr6+-mediated oxidative cyclization, for which a possible mechanism is proposed.

ω-Oxygenated prenylated coumarins from Ferula communis

Abstract From the toxic variety of Ferula communis, derivatives of the prenylated coumarins ferulenol and ferprenin bearing an oxygen function (hydroxyl, acetoxyl, aldehydic carbonyl) at the ω-composition have been isolated. The structures of the coumarins were established by spectral methods and by chemical reactions. Photooxygenation of ferulenol and (E) ω-hydroxyferulenol gave o-hydroxyphenylglyoxylic esters, resulting from the oxidative decarbonylation of the 4-hydroxycoumarinic nucleus and loss of the prenyl side chain. Ethyl o-hydroxyphenylglyoxylate was also isolated from the plant extract, suggesting that a reaction of this type might be responsible for the degradation of the prenylated coumarins in plant samples and extracts of Ferula communis.

Glycerol: a solvent and a building block of choice for microwave and ultrasound irradiation procedures

Glycerol has the potential to be both an excellent renewable solvent in modern chemical processes and a versatile building block in biorefineries. Both of these potential applications may be made easier and more convenient by microwave and/or ultrasound irradiation. As glycerol is a nontoxic, biodegradable compound, it will provide important environmental benefits to new platform products. Furthermore, significant markets in polymers, polyethers, fuel additives, nanoparticles and other valuable compounds may well be opened up by cutting down the high purification cost of glycerol. The aim of this review is to highlight the best literature examples of glycerol being used, either as a solvent or as a reagent, to give interesting results under microwave or ultrasound irradiation.

Click Chemistry Under Microwave or Ultrasound Irradiation

The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is generally recognized as the most striking example of “click reaction”. CuAAC fit so well into Sharpless’ definition that it became almost synonymous with “click chemistry” itself. The most common catalyst systems employ Cu(II) salt in the presence of a reducing agent (i.e. sodium ascorbate) to generate the required Cu(I) catalyst in situ or as an alternative the comproportionation of Cu(II)/Cu(0) species. Although, Cu(I) catalyzes the reaction with a rate enhancement of 10 7 even in the absence of ligands and provides a clean and selective conversion to the 1,4-substituted triazoles, some bulky and scantily reactive substrates still require long reaction times and often few side products are formed. Outstanding results have been achieved by performing CuAAC under microwave (MW) irradiation. Several authors described excellent yields, high purity and short reaction times. In few cases also power ultrasound (US) accelerated the reaction, especially when heterogeneous catalysts or metallic copper are employed. The aim of this review is to summarize and highlight the huge advantages offered by MWand US-promoted CuAAC. In the growing scenario of innovative synthetic strategies, we intend to emphasize the complementary role played by these nonconventional energy sources and click chemistry to achieve process intensification in organic synthesis.

Sesquiterpene coumarin ethers from asafetida

Abstract A commercial sample of Asafetida gave three new sesquiterpene coumarin ethers based on an acyclic terpenoid moiety. The structure of asacoumarin B was revised.

Suzuki cross-couplings of (hetero)aryl chlorides in the solid-state

The ultrasound-assisted cross-linking of chitosan with hexamethylene diisocyanate with the simultaneous incorporation of Pd(OAc)2 resulted in a catalyst which is suitable for the solid-state Suzuki cross-coupling of poorly reactive (hetero)aryl chlorides with phenylboronic acid. Reactions were carried out solvent-free in a planetary ball mill allowing the catalyst to be recycled several times.

Recent advances and perspectives in the synthesis of bioactive coumarins

The impressive pharmacological properties shown by a number of coumarins have led to extraordinarily large emphasis being placed on the design of more efficient and greener synthetic procedures to produce them. The increasing use of enabling technologies, such as microwaves, ultrasound, new heterogeneous catalysts and greener solvents in recent years has made access to coumarin derivatives much simpler. This review will highlight the most recent synthetic advances that make use of non-conventional methods and energy sources and some perspectives for the future, in particular the synthesis of new hybrid molecules bearing a coumarin moiety with a dual mode of biological action.

Sesquiterpenoid esters from the fruits of Ferula communis

Abstract The fruits of the toxic variety of Ferula communis gave a series of 1-oxojaeskeanadiol esters, whose structure was established by spectroscopic data and chemical reactions, including correlation with jaeskeanadiol. Treatment of these esters with potassium hydroxide gave two polienonic products, resulting from the stepwise elimination of the ester group and one water molecule. Both compounds were unstable; the dienone underwent rapid deconjugation via a 1,5-sigmatropic hydrogen shift, whereas the trienone was oxidized in air at the terminal bond of the conjugated system. The toxic prenylated coumarins were not found in the fruits.

Ultrasound-enhanced one-pot synthesis of 3-(Het)arylmethyl-4-hydroxycoumarins in water

3-(Aryl)methyl-4-hydroxycoumarins were produced in good to excellent yields by reaction between 4-hydroxycoumarin and (hetero)aromatic aldehydes in the presence of Hantzsch 1,4-dihydropyridine (HEH) which works as an hydride donor (i.e., in a sequential Knoevenagel-reductive Michael addition). The sonochemical-assisted procedure (method B) provides an improved and accelerated conversion when compared to conventional silent reactions (method A). Experiments carried out according to method B showed that the reaction could be more efficiently run in the absence of organic solvents, at 30-40°C in open vessel, without the need of an excess HEH and with simplified work-up and separation procedures.