A new, modified total synthesis of (−)-cleistenolide (1) and sixteen new analogues or derivatives was achieved starting from commercially available 1,2-O-isopropylidene-α-d-glucofuranose. The synthesis of 1 proceeds in six steps and 67% overall yield, using single-carbon atom degradation of a protected chiral precursor, (Z)-selective Wittig olefination, and acid catalyzed δ-lactonization. A new Lewis acid promoted procedure for one-pot O-debenzylation/O-acylation has been developed to complete the synthesis of natural product 1 and selected analogues. The synthesized compounds were tested in vitro to evaluate their cytotoxicity against K562, HL-60, Jurkat, Raji, MCF-7, MDA-MB 231, HeLa, A549, and MRC-5 cell lines. All (−)-cleistenolide analogues exhibited significantly higher cytotoxicity than lead 1 against the majority of cell lines tested. Most of the synthesized compounds are more active than doxorubicin on at least one malignant cell line, but were almost completely inactive against normal MRC-5 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis.

从可商购获得的1,2 - O-异亚丙基-α - d-葡糖呋喃糖开始，实现了新的（-）-二十碳烯内酯（1）和十六种新的类似物或衍生物的改良全合成。1的合成使用受保护的手性前体的单碳原子降解，（Z）选择性Wittig烯化和酸催化的δ-内酯化过程，分六个步骤进行，总产率为67％。已经开发了一种新的路易斯酸促进的一锅O-去苄基化/ O-酰化方法，以完成天然产物1的合成和选定的类似物。对合成的化合物进行体外测试，以评估其对K562，HL-60，Jurkat，Raji，MCF-7，MDA-MB 231，HeLa，A549和MRC-5细胞系的细胞毒性。对于大多数测试的细胞系，所有（-）-苦杏仁苷类似物均显示出比铅1高得多的细胞毒性。大多数合成的化合物在至少一种恶性细胞系上比阿霉素更具活性，但对正常的MRC-5细胞几乎完全没有活性。通过初步的SAR分析已经确定了负责其抗增殖活性的被测化合物的结构特征。