Molecular Structure and Stereochemistry of Silybin A, Silybin B, Isosilybin A, and Isosilybin B, Isolated from Silybum marianum (Milk Thistle)

Abstract

Two pairs of diastereoisomeric flavonolignans, silybin A, silybin B, isosilybin A, and isosilybin B, were successfully separated from Silybum marianum by sequential silica gel column chromatography, preparative reversed-phase HPLC, and recrystallization. Complete stereochemical assignments at C-2, C-3, C-7', and C-8' of these flavonolignans have been achieved. On the basis of X-ray crystallographic analysis and optical rotation data, coupled with comprehensive (1)H and (13)C NMR spectral data interpretation including COSY, HMQC, and HMBC, the stereochemistry of these diastereoisomers was determined unambiguously as silybin A (4), 2R, 3R, 7'R, 8'R; silybin B (5), 2R, 3R, 7'S, 8'S; isosilybin A (6), 2R, 3R, 7'R, 8'R; and isosilybin B (7), 2R, 3R, 7'S, 8'S.

Structure–Activity Relationship for (+)-Taxifolin Isolated from Silymarin as an Inhibitor of Amyloid β Aggregation

“…The first fraction was chromatographed by high-performance liquid chromatography (HPLC) in a YMC-Pack ODS-A column (20 mm i.d. Â 150 mm; YMC, Kyoto, Japan), using 50% MeOH/H 2 O, to yield silibinin A (1, 16 mg from 240 mg of silymarin, 6.7%) 16) and silibinin B (2, 25 mg from 240 mg of silymarin, 10%), 16) and using 40% MeOH/H 2 O to yield silydianin (3, 31 mg from 370 mg of silymarin, 8.4%. 17) The second fraction was separated in a YMC-Pack ODS-AL column (20 mm i.d.…”

“…The structures of these compounds were confirmed by 1 H-NMR (AVANCE III 500, ref. tetramethylsilane, Bruker, Germany), [16][17][18][19][20] EI-MS (JMS-600H, 70 eV, 300 mA, JEOL, Tokyo, Japan), and specific optical rotation (P-2200, Jasco, Tokyo, Japan).…”

Microbial transformation of silybin by Trichoderma koningii

“…Stereochemistry of the two diastereomers was determined as 2R, 3R, 7 0 R, 8 0 R for silybin A, and 2R, 3R, 7 0 S, 8 0 S for siybin B, respectively. 3,4 Silymarin and its major active constituent, silybin, have been reported to work as antioxidants, which prevent lipid peroxidation and scavenge free radicals, as well as increase hepatocyte protein synthesis and accelerate regeneration in damaged liver. 5 Unfortunately, very low solubility of silybin in water (430 mg/L) has been known to limit its bioavailability in oral administration of this drug.…”

Chymotrypsin Inhibitory Triterpenoids from Silybum marianum

“…The extract was evaporated to yield a residue (750 g), which was partitioned between n-hexane (150 gm), chloroform (80 g), ethyl acetate (55 g), n-butanol (68 g) and water (38 g). The chloroform-soluble fraction was subjected to column chromatography over silica gel with n-hexane-CHCl 3 Tables 1 and 2. IR Table 2.…”