Some 1,3-benzodioxan analogs of chalcones and their epoxides have been obtained, and used to prepare pyrazolines and novel flavone and flavanone analogs of flavolignan (sylibin). The PMR spectra of novel compounds are shown and discussed, together with the results of preliminary biological tests.
Interest in benzodioxan analogs of flavonoids has arisen for the reason that they are related to sylibin, a naturally occurring flavolignan with high biological activity, which possess a benzodioxan moiety in its structure.
In a study of the effects of structural modifications of sylibin on its biological and chemical properties, we have obtained some 1,4-benzodioxan [1-3] and 1,5-benzodioxepan [4] analogs of flavonoids. Some of these showed hypolipidemic, hepatoprotectant, and other types of activity.
We here report the synthesis of some novel flavonoids incorporating the 1,3-benzodioxan nucleus. The starting materials for the preparation of novel flavonoids isomeric with sylibine in respect of the benzodioxan fragment of the molecule were chalcones (I-XVI). These were readily obtained by basic condensation of substituted 2-hydroxy-and 2-benzyloxyacetophenones with 6-halo-l,3-benzodioxanaldehydes. Treatment of chalcones (XIII-XVI) with hydrogen peroxide in alkaline solution gave epoxides (XVII-XX).
These benzodioxan analogs of chalcones (I, III, VIII, X) were converted into the corresponding flavanone analogs (XXI-XXIV) by isomerization on Amberlyst A-21 ion-exchange resin [1].
Oxidation of the propenone (X) with hydrogen peroxide as described in [5] gave the 3-hydroxychromone (XXV). Oxidation of chalcones (I-IV) and (VI-XII) with selenium dioxide in pentanol as described in [6], or with dimethyl sulfoxide in the presence of catalytic amounts of iodine [7], gave satisfactory to good yields of the benzodioxane derivatives of chromones (XXVI-XXXVI). The cyclization times using the latter method were much shorter, and the yields of chromones higher , than when selenium dioxide was used. Several chromones, on treatment with phosphorus pentasulfide in pyridine, were converted into the thioxochromones (XXXVII-XLI).
The structures of (I-X-LI) were established by PMR (Tables 1 and2). The PMR spectra of chalcones (I-XVI) showed signals for the olefinic protons with chemical shifts in the range 7.0-8.0 ppm. The coupling constants (J~,~ 15.8-16.1 Hz) indicate the transoid configuration in all the chalcones prepared. The hydrogen atoms of the hydroxyl groups in (I-XII), which are involved in the formation of intramolecular hydrogen bonds (IMHB), absorb at 12.5-13.4 ppm. *For Communication 12, see [1].