Plant Coumarins: XV.* Oreoselone in the Synthesis of 3-[(Z)-Alkenyl]- and 3-(1H-1,2,3-Triazol-4-yl)psoralens

Sonogashira reaction of 2-isopropyl-3-(trifluoromethanesulfonyloxy)psoralen with terminal arylacetylenes gave 2-isopropyl-3-(arylethynyl)psoralens which were converted into the corresponding Z-alkenes by reduction with hydrogen in the presence of Lindlar catalyst or by thermal decomposition of preliminarily prepared Ti(II)–alkyne complexes. The reaction of 2-isopropyl-3-(trifluoromethanesulfonyloxy)psoralen with trimethylsilylacetylene afforded 2-isopropyl-3-[(trimethylsilyl)ethynyl]psoralen which reacted with 4-(ω-azidoalkyl)phenols in the presence of copper(I) bromide and triethylamine to produce 3-{1-[ω-(4-hydroxyaryl)alkyl]-1H-1,2,3-triazol-4-yl}-2-isopropylpsoralens. * For communication XIV, see [1]. Linear furocoumarins (psoralens) are used for the treatment of skin diseases such as psoriasis, vitiligo, mycoses, and eczema. The main factor responsible for the therapeutic effect of these compounds is photoinitiated cycloaddition of psoralens in the triplet excited state to thymine nucleobases [2, 3]. Some plant furocoumarins, namely bergamottin, xanthotoxin, bergapten, and psoralen possess a considerable cytotoxic potential against various human cancer cell lines [3–6]. In the past decade, much effort has been made to obtain analogs of photochemotherapeutic agents exhibiting photoantiproliferative activity and reduced skin phototoxicity. Various modified derivatives of linear furocoumarins have been synthesized, and new therapeutic applications of the obtained compounds have been found. Promising antimicrobial [7] and selective anticholinesterase agents [8] have been revealed among 2,3,9-trisubstituted psoralens, while glycosylated 3,5-dimethylpsoralens have been reported to show antioxidant activity [9]. 3,5,6-Trisubstituted psoralens are capable of inhibiting HIV-1 integrase [10]. Promising antihypertensive agents have been obtained by varying substituents in the furan ring [11]. Psoralen derivatives inhibiting NF-κB transcription factor, whose deregulation is associated with many diseases (including osteoporosis, rheumatoid arthritis, and cancer), have recently been synthesized [12]. Some 2,3,5,6-substitued psoralens have appeared to be potential precursors of selective anti-inflammatory agents [12]. We have synthesized 3-(Z)-alkenyland 3-[1-(arylalkyl)triazol-4-yl]furocoumarins starting from an accessible furocoumarin, oreoselone (1) [13, 14]. We have recently proposed a procedure for the synthesis of furocoumarins with an aromatic, heterocyclic, (E)-(2-phenylethenyl), or phenylalkynyl substituent on C by palladium-catalyzed cross-coupling of 2-isopropyl-3-(trifluoromethanesulfonyloxy)psoralen (2) [15–18]. (Z)-3-(2-Phenylethenyl)furocoumarins were prepared following the approach [18] including crosscoupling of trifluoromethanesulfonate 2 with terminal alkynes 3a–3e and subsequent partial hydrogenation of the C≡C triple bond (Scheme 1). The conditions for the Sonogashira cross-coupling were optimized using the reaction of 2 with phenylacetylene (3a) as model. The reaction in DMF at 115°C (6 h) in the presence of catalytic amounts of transdichlorobis(tr iphenylphosphine)palladium(II) (10 mol %) and copper(I) iodide (4 mol %) and triethylamine (1.3 equiv) was accompanied by considerable tarring (yield 60%). When the reaction was carried out in THF at 65°C, it was necessary to increase the reaction time to 11 h to attain complete conversion of the initial compound. In this case, the yield of 3-(2-phenylethynyl)furocoumarin (4) was DOI: 10.1134/S1070428015070012X