The first and stereoselective synthesis of xylodonin A and 22-hydroxyxylodonin A, two drimane-type sesquiterpenoid natural products, was developed from the readily available (+)-sclareolide. This route features an allylic oxidation and acid-promoted dehydration for construction of the key intermediate 6-hydroxyisodrimenin. Representative analogues were synthesized, and their previously unknown bioactivities were revealed after biological evaluation. The analogue 19a exhibited cytotoxic activity against liver cancer HepG2 cells (IC₅₀: 8.8 vs 5.9 μM) that was comparable to that of the clinical anticancer drug etoposide with lower toxicity to normal liver HL7702 cells (IC₅₀ > 100 μM).

中文翻译：

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Xylodonin A 和 22-Hydroxyxylodonin A 的立体选择性合成以及具有细胞毒活性的类似物的发现

木糖草宁 A 和 22-羟基木糖草宁 A 这两种二马烷型倍半萜类天然产物的首次立体选择性合成是由容易获得的 (+)-香紫苏内酯开发而成。该路线的特点是烯丙氧化和酸促进脱水，用于构建关键中间体 6-羟基异东梦宁。合成了代表性的类似物，并在生物学评估后揭示了它们以前未知的生物活性。类似物19a对肝癌HepG2细胞表现出细胞毒活性（IC ₅₀：8.8 vs 5.9 μM），与临床抗癌药物依托泊苷相当，对正常肝HL7702细胞的毒性较低（IC ₅₀ > 100 μM）。