RESUMEN
A hitherto unreported member of γ-alkylidenebutenolides in Melodorum fruticosum (Annonaceae), (4 E)-6-benzoyloxy-7-hydroxy-2,4-heptadiene-4-olide, named as isofruticosinol (4) was isolated from the methanol extract of flowers, along with the known related butenolides, namely, the (4 Z)-isomer (3) of 4, melodrinol (1), and its (4 E)-isomer (2). To unambiguously determine the absolute configuration at the C-6 position in these butenolides, the first total syntheses of both enantiomers of 2-4 were achieved over 6-7 steps from commercially available D- or L-ribose (D- and L-5). Using the same protocol, both enantiomers of 1 were also synthesized. Based on chiral HPLC analysis of all synthetic compounds ( S- and R-1-4), all naturally occurring butenolides were assigned as partial racemic mixtures with respect to the chiral center at C-6 (enantiomeric ratio, 6 S/6 R = â¼83/17). Furthermore, the melanogenesis inhibitory activities of S- and R-1-4 were evaluated, with all shown to be potent inhibitors with IC50 values in the range 0.29-2.9 µM, regardless of differences in the stereochemistry at C-6. In particular, S-4 (IC50 = 0.29 µM) and R-4 (0.39 µM) showed potent inhibitory activities compared with that of reference standard arbutin (174 µM).
Asunto(s)
4-Butirolactona/análogos & derivados , Annonaceae/química , Melaninas/biosíntesis , 4-Butirolactona/síntesis química , 4-Butirolactona/química , 4-Butirolactona/farmacología , Animales , Línea Celular Tumoral , Técnicas de Química Sintética , Ratones , Plantas Medicinales/químicaRESUMEN
The first total synthesis of the 7,7-dimethylaporphinoid, 4,5-didehydroguadiscine (6), originally isolated from the stems and roots of Hornschuchia oblique (Annonaceae), was achieved by the condensation of homopiperonylamine (7) with an α,α-dimethylphenylacetic acid derivative (8) and subsequent Pschorr reaction of the resulting benzylisoquinoline intermediate (22). The reported (13)C NMR data were partially revised on the basis of the analysis of HMBC spectra measured under different conditions. The melanogenesis inhibitory activity (IC50 = 4.7 µM) of 6 was 40 times stronger than that of arbutin (174 µM), which was used as reference standard. Furthermore, 6 was the most potent natural melanogenesis inhibitor within this class of compounds.