New .ALPHA.-Tetralonyl Glucosides from the Fruit of Juglans mandshurica

Abstract

Juglans mandshurica MAXIM. (Juglandaceae) is widely distributed throughout urban and rural areas in northeast of China. Its fresh rejuvenated fruit, commonly called "Qing Long Yi", has been used as a folk medicine for treatment of cancer and dermatosis and as an anodyne to relieve aches in China. Although phytochemical analyses were extensively carried out on not only the root [1][2][3][4][5] but also the stem bark 6) of J. mandshurica, little chemical work appears to have been done on the chemical composition of its fresh rejuvenated fruit. To our best knowledge, only two naphthalene glucosides, 4-hydroxynaphthalenyl b-D-glucopyranoside and 4,8-dihydroxy-1-naphthalenyl b-D-glucopyranoside have been isolated from the fruit of J. mandshurica.7) The medicinal uses of "Qing Long Yi" prompted us to investigate its chemical constituents, resulting in the isolation of five new atetralonyl glucosides (1-5). This paper deals with the isolation and structural elucidation of the new compounds on the basis of spectroscopic analysis, including two-dimensional NMR spectroscopic data, and the results of hydrolysis. Results and DiscussionThe fresh rejuvenated fruit of J. mandshurica, which was collected in a mountain area of Heilongjiang Province, China, was decocted twice with water and extracted with hexane, EtOAc and n-BuOH, successively. The n-BuOH extract was chromatographed on a Diaion HP-20 column to give water and 40% methanol eluate fraction. The 40% methanol eluate fraction was chromatographed on an ODS column, and subjected to a combination of silica gel, Lobar RP-C 18 column chromatography, and HPLC. Then, five new compounds, named juglanosides A-E (1-5) were isolated, and their structures were characterized as follows.Juglanoside A (1) was isolated as an amorphous powder. Its molecular formula was determined to be C 16 H 20 O 7 by high-resolution (HR)-FAB-MS. On acid hydrolysis, 1 afforded D-glucose as a component sugar, which was identified by GLC analysis of its trimethylsilyl thiazolidine derivative. The 1 H-NMR spectrum of 1 showed a set of proton signals due to two methylenes at d 3.04 (1H, ddd, Jϭ17.8, 9.5, 4.8 Hz) and 2. 60 (1H, ddd, Jϭ17.8, 6.7, 4.8 Hz), and 2. 44 (1H, dddd, Jϭ13.3, 9.5, 4.8, 3.4 Hz) and 2.36 (1H, dddd, Jϭ13.3, 6.7, 6.2, 4.8 Hz), and an oxymethylene at d 5.10 (1H, dd, Jϭ6.2, 3.4 Hz). Moreover, the 13 C-NMR spectrum, in combination with distortionless enhancement by polarization transfer (DEPT) and Five new a a-tetralonyl glucosides, juglanosides A-E (1-5) were isolated from the fresh rejuvenated fruit of Juglans mandshurica. Their structures were elucidated as (4S)-4-hydroxy-a a-tetralone 4-O-b b-D-glucopyranoside (1), (4S)-4,5-dihydroxy-a a-tetralone 4-O-b b-D-glucopyranoside (2), (4S)-4,6-dihydroxy-a a-tetralone 4-O-b b-D-glucopyranoside (3), (4S)-4,5,8-trihydroxy-a a-tetralone 4-O-b b-D-glucopyranoside (4), and (4S)-4,5,8-trihydroxy-a

Studies on Cytotoxic Activity against HepG-2 Cells of Naphthoquinones from Green Walnut Husks of Juglans mandshurica Maxim

“…There were two sets of high peaks at δH 7.95 (d, J = 8.8 Hz, H-2′′, 6′′), 6.84 (d, J = 8.8 Hz, H-3′′, 5′′), and δC132.9 (C-2′′, 6′′), 116.3 (C-3′′, 5′′) in the 1 H-and 13 C-NMR spectrum, indicating the presence of p-hydroxybenzoly. To determine the absolute configuration of the chiral center at the C-4 position, 25 was hydrolyzed to give the aglycone, which was identified to be S configuration by comparing its NMR data with those of the reference [18,19] and the circular dichrosim CD spectrum, where a negative Cotton effect at 236 nm was observed. On the basis of the above evidence, the structure of 25 was established as (…”

“…The C-6, C-8, and C-10 located in the ortho-and para-position of C-5 were different from compound 25 due to the influence of the hydroxyl group. Moreover, the absolute configuration of 26 was determined as 4S from the CD spectrum of its aglycon [18], which had a negative Cotton effect. Thus, the structure of 26 was established as (4S)-4,5-dihydroxy-α-tetralone-4-…”

“…So we deduced that C-9 and C-3′′, 5′′ occurred in the same position. The absolute configuration of the chiral center at the C-4 position was deduced to be S by CD spectrum analysis of its aglycon [18]. Thus, the structure of 27 was determined to be (4S)-4,5,8-thihydroxy-α- …”

Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation

“…Juglone is used extensively to overcome resistance to chemotherapeutic agents in cancer due to their cytotoxicity (39). For example, the bark, branches and exocarp of the immature green fruit of this medicinal plant have been used to treat gastric cancer, liver cancer, lung cancer and other types of cancer (40). Juglone is also a potent cytotoxic agent in vitro in human tumor cell lines, including human colon carcinoma (HCT-15) cells, human leukemia (HL-60) cells, and doxorubicin-resistant human leukemia (HL-60R) cells (5,41).…”

Anti-proliferative and apoptosis-inducing activities of juglone in LS-174T cells

“…The bark, branches and exocarp of the immature green fruit of walnut trees have been used to treat gastric cancer, liver cancer, lung cancer and other types of cancer for a long time in China (Liu et al, 2004). Juglone has cytotoxic properties when administered to cell cultures (Inbaraj et al, 2004;Kamei et al, 1998;Rippmann et al, 2000;Kiran et al, 2009;Ji et al, 2009.…”