New substituted 4-chloromethylcoumarins that were used as alkylating agents to modify cytisine were synthesized by Pechmann condensation.A series of 4-(12-cytisylmethyl)coumarins containing pharmacophores of the natural heterocycles coumarin and cytisine in a single molecule was prepared. The alkylation gave the best results if diisopropylethylamine was used as the base.In continuation of research on the modification of natural compounds, we decided to investigate the alkaloid (-)-cytisine from seeds of Cytisus laburnum L. and Thermopsis lanceolata R.Br. Cytisine is of great interest to many researchers because of its effect on the ganglionic nervous system and its use in medicine as a respiratory analeptic [1]. A variety of N-alkyl derivatives of cytisine has been synthesized [2-4], among which are compounds with analgesic, antihypertensive, and inotropic activities [3]. According to the patent literature [5], N-methyl derivatives also possess anti-inflammatory and hypoglycemic activities.Therefore, the search for methods of modifying cytisine is very timely. The combination into one molecule of two natural heterocyclic compounds can lead to the production of compounds with new types of physiological activity. Considering this, we selected substituted 4-chloromethylcoumarins, which are used to synthesize compounds with antimicrobial [6] and antiinflammatory [7] properties, as alkylating agents for modifying cytisine. 1, 12: R 1 = R 2 = R 4 = H, R 3 = CH 3 ; 2, 13: R 1 = R 3 = R 4 = H, R 2 = CH 3 ; 3, 14: R 1 = R 2 = H, R 3 = OH, R 4 = CH 3 4, 15: R 1 = R 2 = H, R 3 = R 4 = CH 3 ; 5, 16: R 1 = R 4 = H, R 2 = Cl, R 3 = CH 3 ; 6, 17: R 1 = R 4 = H, R 2 = OH, R 3 = CH 3 7, 18: R 1 = R 3 = CH 3 , R 2 = R 4 = H; 8,19: R 1 = R 3 = H, R 2 = R 4 = CH 3 ; 9, 20: R 1 = R 3 = R 4 = H, R 3 = CH 2 CH 3 10, 21: R 1 = R 4 = H, R 2 R 3 = CH 2 CH 2 CH 2 ; 11, 22: R 1 = R 4 = H, R 2 = R 3 = CH 3 Several synthetic methods for 4-chloromethylcoumarins are known. These include the reaction of phenols with 4-chloroacetoacetic ester in H 2 SO 4 (Pechmann condensation) [8-10], chlorination of coumarin-4-acetic acid in AcOH [11], and reaction of 4-hydroxymethylcoumarins with PCl 5 in benzene [8,12]. Based on the literature, we selected the Pechmann condensation for preparing 4-chloromethylcoumarins 1-11.
