Oxidation of usninic acid

Abstract

Reactions of usninic acid with various oxidants were studied. The oxidation occurred at the resorcinol ring. New derivatives of usninic acid were obtained from reactions with per-acids.The isolation of plant metabolites and their chemical modification to produce novel drug candidates with high physiological activity is an active area in natural product chemistry.An interesting subject for chemical modification is usninic acid (UA) (1), the principal constituent in extracts of most lichens and a compound with a broad spectrum of biological activity. Interest in UA has been unwavering for many decades [1]. Nevertheless, reactions involving oxidation of UA or its derivatives have been little studied. Thus, cleavage of the carbon skeleton of UA in the presence of base in alcohol and aqueous alcohol was reported [2][3][4][5]. Under these conditions, different researchers have obtained complicated mixtures of products, several of which were isolated in small yields. Oxidation of UA 7,9-diacetate by KMnO 4 occurred at ring C and also gave a complicated product mixture [6]. The action of H 2 O 2 on UA was studied [7]. The reaction was carried out in pyridine and formed the 2-acetoxy derivative (83% yield).Herein we report results from the reaction of UA with various oxidants. Reactions of 1 with conc. HNO 3 and CrO 3 reagents gave complicated product mixtures that resulted apparently from extensive destruction of the substrate.On the other hand, 1 was not oxidized in the presence of oxidants such as Pb(CH 3 COO) 4 , KIO 4 , O 2 , t-BuOOH, DessMartin periodinan, H 2 O 2 in CHCl 3 (in the presence of TEBA), and SeO 2 in the presence of H 2 O 2 .The oxidation occurred at room temperature and formed two compounds if organic per-acids (MCPBA, CH 3 CO 3 H, MPPA) in CHCl 3 were used as oxidants. The products were most conveniently isolated from CH 3 CO 3 H because its decomposition product, CH 3 CO 2 H, was easily removed from the reaction mixture by washing with water. If MCPBA or MPPA were used, the products were difficult to isolate from the m-chlorobenzoic or phthalic acids, respectively, formed during the reaction because the standard work up with NaHCO 3 solution removed part of the UA oxidation products with the aqueous phase. Column chromatography over silica gel isolated 2 and 3 in yields of 41 and 27%, respectively (Scheme 1).