Silybins synthesis

Sigmatropic rearrangement 677, 697 Sihca gel membranes 1082 Silphinene, electrosynthesis of 1183, 1187 Silver compounds, as oxidants 1307-1311 Silybin, synthesis of 1308, 1310 Silydianin 1180 Silylation, of phenols 934, 935 Silylcyanation, asymmetric 694, 695, 702 Simmons-Smith cyclopropanation, asymmetric 694... 

Benzodioxanes (6, 516). The earlier synthesis of benzodioxanes by oxidative coupling of catechol derivatives with methoxypropenylphenols has been extended to the first synthesis of the complex benzodioxane silybin (3) shown in equation (I).2 The starting materials are (2R,3R)-dihydroqucrcctin (I) and coniferyl alcohol (2). In this case, the reaction is not regioselective, 3 and the isomeric 4 being obtained in nearly equal amounts. 

In the early years after the discovery of silybin (1), the structure determination of this compound class was mainly achieved through extensive chemical conversions and degradative reactions (15, 95), which often led to structures that later needed revision. Analysis of comprehensive spectroscopic data along with classical chemical reactions and synthesis approaches has led to the unequivocal determination of the absolute stmctures of flavonolignans (102,135). The complete structure elucidation of flavonolignans is summarized below. 

The structure 1 proposed for silybin was supported from its mass spectmm, which showed fragment ions at/n/z 302 (H) and 180 (I), formed by RDA cleavage of the dioxane bridge of the molecule (Table 16). The trans configurations of H-2, H-3 and H-7", H-8" were resolved from their coupling constant values (/ = 11.3 and 7.9 Hz). Stmcture 1 assigned was finally confirmed by the synthesis of... 

The liver-protective effect of silymarin is multifactorial and this may be due to its antidote, antifibrogenic, membrane stabilizing, protein synthesis inducing, and signal-evoking properties (90). Silymarin and silybin (1) have also shown potential... 

Merlini L, Zanarotti A, Pelter A, Rocheport MP (1979) Biomimetic Synthesis of Natural Silybin. J Chem Soc Chem Commun 695... 

Tanaka H, Shibata M, Ohira K, Ito K (1985) Total Synthesis of ( )-Silybin, an Antihepa-totoxic Flavonolignan. Chem. Pharm. Bull. 33 1419... 

Intramolecular oxidative coupling of phenols (6, 516). A biomimetic synthesis of natural silybin (3), an interesting antihepatotoxic agent, involves oxidation of a mixture of optically active 1 and coniferyl alcohol (2) with AgO in a benzene-acetone mixture at 55°. This reaction affords a mixture of silybin (3) and isosilybin (4) in 78% yield. The products 3 and 4 are diastereomeric mixtures at C2 and Cs- relative to C2 and... 

The silymarin complex is aptly suited for its hepatuprotec-tivc actions. Silymarin undergoes enterohepatic cycling, moving from intestine to liver and concentrating in liver cells. Protein. synthesis is induced in the liver by. silybin. 

Highly reactive quinone methide can be utilized as intermediates in organic synthesis. From the viewpoint of biomimetic synthesis, silybin (782) bearing a benzodioxane skeleton was synthesized in 44.5% yield, together with isosilybin (784) (33.5%), by AgiO-mediated oxidation of equimolar amounts of 27 ,37 -dihydroquercetin (783) and coniferyl alcohol (298) in benzene-acetone. The p-quinone methide 785 must be generated as a reactive intermediate (Scheme 156) °. 

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