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We have previously reported the preparation of several coumarins and furocoumarins modified with amino acids. In continuation of this work, we investigated the synthesis of substances in which a dipeptide would be added to the benzopyran core.Starting 3,4-disubstituted 7-hydroxycoumarins were synthesized by Pechmann condensation of the corresponding resorcinols and esters of substituted β-ketoacids in the presence of H 2 SO 4 as condensing agent [3,4]. PMR spectra of the starting coumarins contained resonances typical of the coumarin system and its substituents.Williamson reaction of the 7-hydroxycoumarins with methylchloroacetate using potash as the base produced the corresponding esters of substituted 2-oxo-2H-7-chromenyloxyacetic acids. The esters were hydrolyzed by heating with sodium bicarbonate solution (5%). The structures of the resulting acids were confirmed by PMR spectroscopy. The spectra of the products (11-20) lacked a resonance for the hydroxyl proton of the starting 7-hydroxycoumarins and contained resonances for the acetic acid as a very broad singlet for the carboxyl at 12.0-12.5 ppm and a resonance for the α-CH 2 protons at 4.5-5.0 ppm.Dipeptide derivatives of 11-20 could be prepared by two routes, addition of the dipeptide or successive elongation of the peptide chain. We used activated esters to synthesize the amino-acid derivatives. These are used widely in peptide synthesis [5] to activate the carboxyl using the N-hydroxysuccinimide (NHS) ester, which is highly reactive and does not racemize the products.Reaction of 11-20 with NHS in absolute dioxane using diisopropylcarbodiimide as the condensing agent produced the corresponding NHS esters. Compounds 21-36 were synthesized by reaction of the NHS esters with sodium salts of glycylglycine (21-30), norleucine (31), leucine (32), and β-alanine (33) in dioxane:water (1:1) with subsequent acidolysis of the resulting salts. The isolated amino-acid derivatives had a free carboxylic acid that could be activated analogously for addition of the next amino acid. Compounds 34-36 were prepared this way. PMR spectra of the isolated compounds contained resonances for the coumarin ring, the dipeptide, amide bonds at 8.02-8.46 ppm, and the carboxylic acid at 12.11-12.69 ppm.

New indan-1-one derivatives (8 examples) with amino acid fragments were synthesized through the N-acylation of the amino acids by 2-(3-oxo-2,3-dihydro-1H-inden-5-yloxy)acetic acid using the method of activated N-hydroxysuccinimide esters. To obtain corresponding methyl esters (2 examples) two ways were possible: the N-acylation of the amino acid methyl esters by 2-(3-oxo-2,3-dihydro-1-inden-5-yloxy)acetic acid through the activated imidazole derivatives or methylation of the carboxylic function of preformed N-{[(1-oxoindan-6-yl)oxy]acetyl}amino acids.

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