Plant coumarins: VIII. Suzuki reaction in the synthesis of 3-aryl(hetaryl)furocoumarins

Abstract

Suzuki cross coupling of oreoselone trifluoromethanesulfonate with substituted phenyl-and hetarylboronic acids in the presence of palladium complexes with uni-and bidentate ligands gave the corresponding 3-substituted furocoumarins. * For communication VII, see [1].Natural linear furocoumarins such as psoralen and 8-methoxypsoralen are traditionally used as photochemotherapeutic agents in PUVA therapy of skin diseases, in particular of psoriasis, vitiligo, and atopic eczema [2]. However, their application in combination with UV irradiation gives rise to side effects (mutagenic etc.), so that search for new psoralen derivatives is strongly desirable. It was found that application of synthetic derivatives, e.g., of 3-ethoxycarbonylpsoralen, reduces side effects in therapy of skin diseases [3]. Derivatives of 3-alkyl-and 3-aryl-substituted furocoumarins are known as inhibitors of leukotriene LTB 4 biosynthesis, and they may be promising from the viewpoint of design of anti-inflammatory photoactive agents [4]. In addition, extensive search for Kv-1.3 potassium channel blockers is performed in the series of amino-substituted furocoumarins [5]. Garazd et al.[6] synthesized 3-aryl-substituted furocoumarins which exhibited cardiotropic activity [6].3-Aryl-substituted linear furocoumarins were synthesized according to MacLeod (Williamson reaction of 7-hydroxycoumarins with α-halo ketones in the presence of K 2 CO 3 and cyclization in the presence of 1 N NaOH with subsequent acidolysis [4][5][6][7]). This approach includes a number of steps and requires the corresponding 7-hydroxycoumarins as starting compounds. In the present work we made an attempt to synthesize furocoumarin derivatives containing an aromatic or heteroaromatic substituent on C 3 by palladium-catalyzed cross-coupling of oreoselone trifluoromethanesulfonate (I) with boronic acid (Suzuki reaction). 4-Halo-and 4-trifluoromethylsulfonyloxycoumarins were successfully involved in Suzuki-Miyaura reaction to synthesize 4-aryl(hetaryl or alkynyl)coumarins [8,9], while analogous reactions with substituted furocoumarins were not reported previously.Cross-coupling of oreoselone trifluoromethanesulfonate (I) with o-tolylboronic acid (II) was used as

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

“…The reaction in both cases turned out to be sensitive to substituents in the aryl fragment of boronic acid. The reaction resulted in the synthesis of series of 3-aryl-or 3-hetarylpsoralenes 32 [24] or 7-(het)arylsubstituted coumarins 31 [23].…”

Plant coumarins: XV. Oreoselone in the synthesis of 3-[(Z)-alkenyl]- and 3-(1H-1,2,3-triazol-4-yl)psoralens

“…We have recently proposed a procedure for the synthesis of furocoumarins with an aromatic, heterocyclic, (E)-(2-phenylethenyl), or phenylalkynyl substituent on C 3 by palladium-catalyzed cross-coupling of 2-isopropyl-3-(trifluoromethanesulfonyloxy)psoralen (2) [15][16][17][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).…”