Abstract
A number of new derivatives of o-alkoxy cinnamic acids were obtained from various coumarins by opening the lactone fragment and O-alkylation of the endocyclic Oxygen atom.
The α-hetaryl-β-(2-alkoxy-5-chlorophenyl)cinnamic acids were obtained from 3-(benzothiazol-2-yl)-6-chlorocoumarin and 3-(benzimidazol-2-yl)-6-chlorocoumarin by treatment with diluted alkali followed by p-methylbenzyl chloride or dimethyl sulfate addition, respectively.
A similar reaction stages (opening in aqueous alkali and alkylation of the phenolate anion) was applied to the synthetic analogues of psoralen – 5-methylfuro[3,2-g]coumarins with various substituents in the furan fragment. Thus it was possible to obtain a number of 3- and 4-substituted 3-(6-alkoxybenzofuran-5-yl)but-2-enoic acids. But in this case, the conversion of the starting furo[3,2-g]coumarins to cinnamic acid derivatives was not complete even after long time of reaction with a big excess of an alkylation agent. Therefore, the necessary step is the separation of the target acid from unreacted coumarin by dissolving the product in a saturated NaHCO3 solution. The insoluble part is a practically pure starting material, which can be recycled in the reaction; so the total yield of the product would be increased. To demonstrate the synthetic abilities of 3-(6-alkoxybenzofuran-5-yl)but-2-enoic acids these compounds were used in synthesis of amides with pharmacophore fragments: a phenethylamine derivative with an additional sulfamide group and a β-alanine derivative.
The experiments showed that the 3-azolylcoumarins and furo[3,2-g]coumarins coumarin cycle's opening occurs only in aqueous alkali, and when alkylated in an organic solvent in the presence of K2CO3, the lactone fragment remains unchanged. The 7-hydroxy-6-(isocoumarin-3-yl)-4-methylcoumarin cycle turned out to be more labile. The result of alkylation of this compound with ethyl acetate of chloroacetic acid in the presence of K2CO3 depended on the nature of the aprotic solvent and the temperature of reaction. So, when this reaction was carried out in boiling acetone, only the free hydroxyl group at position 7 of coumarin was alkylated. But when the initial coumarin was heated at 100°С with an excess of an alkylating agent in DMSO, simultaneous alkylation of both the free 7-OH group and the endocyclic Oxygen atom occurred.
Publisher
Taras Shevchenko National University of Kyiv
Subject
Pharmacology (medical),Complementary and alternative medicine,Pharmaceutical Science
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