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As a result of the reaction of resorcinols with dimethyl acetonedicarboxylate under the conditions of the Pechmann reaction derivatives of 4,4'-spirodichroman-2-one were isolated as anomalous condensation products. Their structure was demonstrated by spectral methods. A mechanism was proposed for the formation of the spirodilactone system.The reaction of phenols and the esters of β-keto acids in the presence of dehydrating agents such as concentrated sulfuric acid is known as the Pechmann reaction [1]. This condensation has found widespread use in the synthesis of compounds based on the benzopyran-2-one system [2,3]. The course of the reaction and the structure of the products depend on the nature of the phenols and the β-keto esters and also on the nature of the condensing agent. The Pechmann reaction can also give other products and, in particular, chromones, diarylglutamic acids and their anhydrides, dilactones, etc. [1,4].In the reaction of resorcinol and dimethyl acetonedicarboxylate in methanol in the presence of concentrated sulfuric acid as condensing agent, in addition to the expected product of the Pechmann reaction [methyl 7-hydroxycoumarin-4-acetate (1)] we also obtained a 16% yield of the product 2, which differed from the benzopyran-2-one derivatives in its spectral characteristics. In the UV spectrum of compound 2 there is one strong absorption maximum at 204 nm, whereas the derivatives of the 7-hydroxycoumarins have two strong maxima at 210-225 and 310-325 nm [5]. In the IR spectrum of compound 2 there are strong bands at 1745 (characteristic of the saturated lactone) and 3435 cm −1 (due to the stretching vibrations of the phenol group). The 1 H NMR spectrum of the product 2 in the region of the aromatic protons contains a system of ABX protons, a broad one-proton singlet for the hydroxy group at 9.81 ppm, and two one-proton doublets with J = 15.0 Hz at 2.97 and 3.16 ppm. The 13 C NMR spectrum contains a signal at 38.20 ppm for the quaternary carbon atom. A molcular-ion peak of high intensity with m/z 312 [M] + (96%) is observed in the mass spectrum of compound 2. Compound 2 is consequently 4,4'-spirodi[7-hydroxychroman-2-one].During the condensation of 2-methylresorcinol and dimethyl acetonedicarboxylate under analogous conditions methyl 7-hydroxy-8-methylcoumarin-4-acetate (3) and 4,4'-spirodi[7-hydroxy-8-methylchroman-2-one] (4) were isolated with yields of 64 and 11% respectively. __________________________________________________________________________________________

N-Acetyl derivatives of cytisine modified by coumarins were synthesized.Adding a natural alkaloidal fragment to organic molecules leads in most instances to the appearance of new biological properties. Cytisine possesses potent pharmacological activity [1,2]. On the other hand, coumarins form a group of structurally varied natural bioregulators of plant origin that are based on the benzopyran-2-one skeleton [3]. Depending on the structure, natural coumarins and their synthetic analogs possess a wide spectrum of biological activity [4]. We synthesized a series of cytisine derivatives that contain the coumarin moiety, a heterocycle that is widely distributed in nature.Hydroxycoumarins 1-8 that were required for further transformations were prepared by Pechmann condensation of polyphenols (resorcinol, 2-methylresorcinol, orcine) and ethyl-2-oxocyclopentanecarboxylate or ethyl-2-oxocyclohexanecarboxylate in the presence of conc. H 2 SO 4 [5, 6].Alkylation of 1-8 in acetone in the presence of potash by ethylchloroacetate produced ethyl esters 9-16, saponification of which by NaOH in aqueous propan-2-ol with subsequent acidolysis gave the corresponding acids 17-24.Cytisine was modified by two methods. The first method of cytisine N-acylation was based on the method of activated esters that is widely applied in peptide synthesis [7]. We used the highly reactive N-hydroxysuccinimide ester to activate the carboxylic function [8]. Activated esters were prepared by reacting corresponding acids 17-24 and N-hydroxysuccinimide (SuOH) in absolute dioxane using diisopropylcarbodiimide (DIC) as the condensing agent. Condensation of the resulting esters with cytisine in dioxane at room temperature formed in high yields the N-acyl cytisine derivatives 25-32, which contain coumarin moieties.The second method was based on activation of the carboxylic function of coumarinyloxyacetic acids using N,N-carbonyldiimidazole (CDI) [9,10]. Reaction of acids 17-24 and CDI in absolute DMF formed N-acylimidazoles, which were converted in high yields and smoothly by cytisine to the corresponding N-acyl cytisine derivatives 25-32.Analysis of PMR spectra revealed that a doubled set of signals was found for all prepared compounds. Obviously formation of amide bonds in such systems produces invertomers with hindered rotation around the N-C bond that can be considered to be Z-and E-isomers. The presence of amide conjugation was confirmed by temperature experiments. Thus, heating samples of the prepared compounds to 100°C caused signals in the PMR spectrum to coalesce because of free rotation of the substituents around the N-C bond.