Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.
J Nat Med. 2018 Jun;72(3):651-654. doi: 10.1007/s11418-018-1198-6. Epub 2018 Mar 5.
Lignans are widely distributed in plants and exhibit significant pharmacological effects, including anti-tumor and antioxidative activities. Here, we describe the total synthesis of schizandriside (1), a compound we previously isolated from Saraca asoca by monitoring antioxidative activity using the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Starting from a tandem Michael-aldol reaction, the lignan skeleton was synthesized in 6 steps, including a cyclization step. To determine the stereochemistry of 1, we synthesized the natural product (±)-isolariciresinol (18) from alcohol 17. Comparison of the spectral data showed good agreement. Glycosylation was investigated using four different glycosyl donors. Only the Koenigs-Knorr condition using silver trifluoromethanesulfonate with 1,1,3,3-tetramethylurea provided the glycosylated product. Deprotection and purification using reverse-phase high-performance liquid chromatography gave schizandriside (1) and its diastereomer saracoside (2). Synthesized 1, 2 and 18 showed antioxidant activity with IC = 34.4, 28.8, 53.0 μM, respectively.
木脂素广泛存在于植物中，具有显著的药理作用，包括抗肿瘤和抗氧化活性。在这里，我们描述了五味子酯（1）的全合成，这是我们之前通过使用 1,1-二苯基-2-苦基肼自由基清除试验监测抗氧化活性从 Saraca asoca 中分离得到的一种化合物。从串联迈克尔-羟醛缩合反应开始，经过 6 步合成，包括环化步骤，合成了木脂素骨架。为了确定 1 的立体化学，我们从醇 17 合成了天然产物（±）-异松脂醇（18）。比较光谱数据表明吻合良好。我们用四种不同的糖基供体研究了糖苷化。只有使用银三氟甲磺酸和 1,1,3,3-四甲基脲的 Koenigs-Knorr 条件提供了糖苷化产物。使用反相高效液相色谱进行脱保护和纯化得到五味子酯（1）及其差向异构体五味子酯（2）。合成的 1、2 和 18 的抗氧化活性的 IC50 值分别为 34.4、28.8 和 53.0 μM。
