Plant coumarins. 4.* Synthesis of N-containing derivatives of oreoselone

Abstract

dione were found. Several 2-aminofuranocoumarins were synthesized by reaction of 2-bromoreoselone with derivatives of pyrrolidine, piperidine, and piperazine. The new compounds were interesting as potential biologically active compounds.Linear dihydrofuranocoumarins are widely distributed plant metabolites with pronounced biological activity [2][3][4]. Thus, marmesin (1) is an effective c-AMP synthetase [5] and acetylcholinesterase [6] inhibitor. Propanediol (2) is used as an antidote to snake venom [7]. The potential of coumarins for creating new antioxidants has recently been actively discussed owing to their specific activity as selective MAO inhibitors [8]. Thus, the development of methods for modifying furanocoumarins is of definite interest in medicinal chemistry.An accessible source of furanocoumarins is Peucedanum morisonii Bess., which is widely distributed in western Siberia. Its main metabolite peucedanin (3) can be isolated from roots of the plant in yields up to 4% of the dry raw material mass [9]. The preparation of several derivatives of peucedanin and its hydrolysis product oreoselone (4) through modification of the furan ring has been reported [10,11]. Herein we describe the synthesis of new oreoselone derivatives.The starting material for the transformations was 2-bromoreoselone (5), which was formed by bromination of 3 with Br 2 in CHCl 3 , as previously reported [10]. We found that 5 was also the only product from bromination of peucedanin by Br 2 in formic acid (98% yield), by dioxanedibromide in CCl 4 (94-98% yield), by N-bromosuccinimide in CCl 4 (97-98% yield), and by pyridine dichlorobromate (PyHBrCl 2 ) in CH 3 OH (94% yield). Subsequent bromination of 5 by NBS (3 equiv.) in the presence of benzoyl peroxide in CCl 4 formed 2-(1,3-dibromopropan-2-ylidene)-2H-furo[3,2-g][1]benzopyran-3,7-dione (6) (73% yield). Obviously benzoyl peroxide enhances dehydrobromination of 2-bromoreoselone and subsequent allylic bromination. This was confirmed by the fact that 6 was formed by bromination of known 2-(1-methylethylidene)-7H-furo[3,2-g][1]benzopyran-3,7-dione (7) under these conditions [10, 12] (51% yield).

Modification of Biologically Active Plant Metabolites Via the Transition Metal Catalyzed Reactions

“…Dibromide 91 obtained from peucedanin 6 [30] was used for the amination with various amino derivatives [31] (Scheme 14). The reaction of 2-(1,3-dibromoprop-2-ylidene)oreoselone 77 with L-or D-valinol catalyzed by the system Pd(OAс) 2 -BINAP in DMF in the presence of Et 3 N allowed us to obtain diamino derivatives 78 and 79 in 72 and 64% yields, respectively.…”