Silvia L. Debenedetti

Synthesis of coumarins by ring-closing metathesis using Grubbs’ catalyst

A novel generally applicable synthesis of coumarins from phenolic substrates utilizing ring-closing metathesis is described. This sequence involves O-allylation of phenols followed by ortho-Claisen rearrangement, subsequent based-induced isomerization affording 2-(1-propenyl)phenols, acylation with acryloyl chloride, and finally ring-closing metathesis (RCM) with Grubbs’ second generation catalyst.

Caffeoylquinic acids from Pterocaulon virgatum and Pluchea sagittalis

Pterocaulon virgatum (L.) DC. and Pluchea sagittalis (Lam.) Cabrera (common name ‘lucera’) are two Compositae widely distributed in the northeastern region of Argentina [l]. They are used in folk medicine due to their tonic, sour and digestive properties ([2, 31; Bowes, N., personal communication). Infusions of P. sugittalis have been described as colagogue and choleretic when given to patients with liver and gall-bladder problems [4]. In a previous paper we have reported the isolation of a flavone from P. sagittalis [S]. The present paper reports the isolation of 3,klicafieoylquinic acid (yield 1%) from P. uirgattun and isochlorogenic acid (yield 0.2 %) (a mixture of 3,4-; 4,5and 3,5&ATeoylquinic acid) from P. sagittalis. This is the first report of 3,4-dicaffeoylquinic acid as a single product; it always occurs in other sources with its isomers. Caffeic acid and its esters have proved to increase bile flow in rats [6, 71. The medicinal properties of these plants are presumably related to the high content of caffeic acid esters found in them.

Synthesis of 6-methoxy-4H-1-benzopyran-7-ol, a character donating component of the fragrance of Wisteria sinensis.

Abstract 6-Methoxy-4H-1-benzopyran-7-ol 7 , a major impact flavor compound of Wisteria sinensis has been synthesized from 2,4,5-trimethoxybenzaldehyde 1 via scopoletin 3 . The synthetic sequence comprised (i) bisdemethylation of 2,4,5-trimethoxybenzaldehyde 1 , (ii) Wittig reaction with ethoxycarbonylmethylenetriphenylphosphorane, (iii) hydrogenation on palladium/carbon in glacial acetic acid, (iv) DIBAL-H reduction of the intermediate lactone and (v) dehydration of the lactol with anhydrous oxalic acid.

Toward establishing structure-activity relationships for oxygenated coumarins as differentiation inducers of promonocytic leukemic cells

The presumption that some coumarins might be lead compounds in the search for new differentiation agents against leukemia is based on the fact that natural coumarins, 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin (C-2) and 5-methoxy-6,7-methylenedioxycoumarin (C-1) inhibit proliferation and induce differentiation in U-937 cells [Riveiro, M. E.; Shayo, C.; Monczor, F.; Fernandez, N.; Baldi, A.; De Kimpe, N.; Rossi, J.; Debenedetti, S.; Davio, C. Cancer Lett.2004, 210, 179-188]. These promising findings prompted us to investigate the anti-leukemia activity of a broader range of related polyoxygenated coumarins. Twenty related natural or synthetically prepared coumarins, including a range of 5-substituted ayapin derivatives which have become easy accessible via newly developed synthesis methods, were evaluated, where treatments with 5-(2,3-dihydroxy-3-methylbutoxy)-6,7-methylenedioxycoumarin (D-3) and 5-(2-hydroxy-3-methoxy-3-methylbutoxy)-6,7-methylenedioxycoumarin (D-2) were able to inhibit the cell growth and induce the differentiation of U-937 cells after 48 h treatment. These results provide insight into the correlation between some structural properties of polyoxygenated coumarins and their in vitro leukemic differentiation activity.

Two 6,7-dioxygenated coumarins from Pterocaulon virgatum

Abstract From the petrol and chloroform extracts of the aerial parts of Pterocaulon virgatum , two new coumarins, virgatenol and virgatol, were isolated, as well as the four known coumarins, 7-(3-methyl-2-but-enyloxy)-6-methoxycoumarin, 7-(2,3-dihydroxy-3-methylbutoxy)-6-methoxycoumarin, ayapin (6,7-methy-lenedioxycoumarin) and scopoletin (7-hydroxy-6-methoxycoumarin). Their structures were elucidated on the basis of spectroscopic methods.

Structural revision of four coumarins from Pterocaulon species

Abstract The structures of two 5,6,7-trioxygenated coumarins named sabandinol and sabandinone isolated from Pterocaulon virgatum have been revised. The new structures assigned were regioisomers and were identified on the basis of additional spectroscopic data and X-ray crystallographic data. Also the structural revision of two trioxygenated coumarins from Pterocaulon balansae and P. lanatum is presented.

Topical anti-inflammatory activity of Gentianella achalensis

The anti-inflammatory activity of the petrol, dichloromethane and methanol extracts from Gentianella achalensis flowering plant were studied using 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice and carrageenan-induced paw edema in rats. Only the dichloromethane extract and its F2 fraction (at 1 mg/ear) showed marked anti-inflammatory activity in TPA-induced ear edema test. No effects were seen on carrageenan-induced edema. Oleanolic and ursolic acid, isolated from F2, may account for the observed topical anti-inflammatory effects.

Isopurpurasol, a coumarin from Pterocaulon virgatum

A new 5,6,7-trioxygenated coumarin, named isopurpurasol, was isolated from the chloroform extracts of the aerial parts of Pterocaulon virgatum. The structural elucidation of this regioisomer of purpurasol was performed by detailed spectroscopic analysis.

Antifungal activity of Terminalia australis

Dichloromethane, methanol and aqueous extracts of the aerial parts of Terminalia australis were evaluated for their antifungal activity. The methanol and aqueous extracts were found to be effective against the tested Aspergillus and Candida strains.

Revision of the structure of obtusifol

Abstract The recently isolated 6,7,8-trioxygenated coumarin, named purpurasol, has been shown to be identical to the previously reported obtusifol. The structure of purpurasol has been confirmed and that of obtusifol revised for a second time.