三尖杉二萜类天然产物的全合成研究进展

doi:10.6023/cjoc202408007

摘要/Abstract

对三尖杉属植物的持续研究最终促成了高三尖杉酯碱在2012年获得美国食品药品监督管理局(FDA)批准, 用于治疗慢性髓性白血病, 而三尖杉属植物中另一大类天然产物三尖杉二萜的研究同样重要. 自1978年发现第一个成员harringtonolide以来, 三尖杉二萜因其显著的抗癌活性, 引起了科学界的广泛关注. 三尖杉二萜的独特结构特征7/6/5/6稠合的四环碳骨架和桥环内酯, 使其成为合成化学家的理想目标. 成功合成这类复杂二萜对于抗肿瘤药物的发现和开发具有重要意义, 迄今为止, 已有10个研究团队完成了24个三尖杉二萜的全合成. 综述了三尖杉二萜全合成的最新进展, 展示了这些创造性的合成策略以及在复杂天然产物高效合成中的重要性, 以及它们在推动药物发现领域中的潜力和意义.

关键词: 三尖杉二萜, 全合成, 抗肿瘤活性, harringtonolide, 三尖杉

Continuous research on Cephalotaxus plants has ultimately led to the US food and drug administration (FDA) approval of homoharringtonine in 2012 for the treatment of chronic myeloid leukemia. Additionally, another important class of natural products from Cephalotaxus plants is cephalotane diterpenoids. Since the discovery of the first member, harringtonolide, in 1978, cephalotane diterpenoids have garnered significant attention from the scientific community due to their remarkable anti-cancer activity. The unique structural features of cephalotane diterpenoids, a 7/6/5/6-fused tetracyclic carbon skeleton and a bridged lactone, make them ideal targets for synthetic chemists. Successfully synthesizing these complex diterpenoids is of great importance for the discovery and development of anti-tumor drugs. To date, ten research groups have completed the total synthesis of 24 cephalotane diterpenoids. The latest progress in the total synthesis of cephalotane diterpenoids is reviewed, showcasing the importance of these innovative synthetic strategies in the efficient synthesis of complex natural products and their potential significance in advancing the field of drug discovery.

Key words: cephalotane diterpenoids, total synthesis, anti-cancer activity, harringtonolide, Cephalotaxus

引用此文

丁一鸣, 张庭荣, 张泾渭, 邓军. 三尖杉二萜类天然产物的全合成研究进展[J]. 有机化学, 2025, 45(6): 2048-2073.

Yiming Ding, Tingrong Zhang, Jingwei Zhang, Jun Deng. Progress in the Total Synthesis of Cephalotane Diterpenoid Natural Products[J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2048-2073.

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图/表 27

Figure 1. Representative structures of cephalotane diterpenoids

Scheme 1. Nay, Yue and Cai's proposed biosynthetic proposals for Cephalotaxus troponoids

Scheme 2. Dai's proposed biosynthetic pathway to cephalotene from GGPP

Scheme 3. Yue's proposed biosynthetic pathway to the dimerization of cephalotane-type C19-norditerpenoids

Scheme 4. Total synthesis of (±)-hainanolidol by Mander's group

Scheme 5. Total synthesis of (±)-cephinoid H and (±)-fortalpinoid C by Zhao's group

Scheme 6. Total synthesis of (±)-cephanolide E by Zhao's group

Scheme 7. Synthesis of (±)-harringtonolide by Sarpong's group

Scheme 8. Total synthesis of (±)-cephanolide A and (±)-harringtonolide by Wang's group

Scheme 9. Total synthesis of (±)-hainanolidol and (±)-harringtonolide by Tang's group

Scheme 10. Total synthesis of (＋)-harringtonolide by Zhai's group

Scheme 11. Semi-synthesis of (－)-cephalodiones B~D by Yue's Group

Scheme 12. Total synthesis of (±)-cephanolides A~D by Sarpong's group

Scheme 13. Total synthesis of benzenoid cephalotane-type norditerpenoids by Sarpong's group

Scheme 14. Total synthesis of (－)-cephanolides A and B by Cai's group

Scheme 15. Total synthesis of (＋)-fortalpinoid A, (＋)-cephinoid H, (＋)-3-deoxyfortalpinoid F by Hu's group

Scheme 16. Total synthesis of (±)-cephanolide B by Yang's/Zhang's group

Scheme 17. Total synthesis of (－)-cephanolides B~D and (－)-ceforalide B by Hu's group

Scheme 18. Total synthesis of (－)-cephinoid P, (－)-cephafortoid A, (－)-fortalpinoids M, N, P by Gao's group

Scheme 19. Total synthesis of (－)-cephalotanin B by Hu's group

Scheme 20. Total syntheses of (＋)-3-deoxyfortalpinoid F, (－)-fortapinoids M/N/P, (＋)-harringtonolide by Hu's group

Scheme 21. Total synthesis of (±)-cephanolides B and C by Zhao's group

Scheme 22. Total synthesis of (＋)-mannolide C by Zhai's group

Scheme 23. Total synthesis of (－)-cephanolides A~D by Zhai's group

Scheme 24. Total synthesis of (－)-cephanolides A and B by Gao's group

Scheme 25-1. Key strategies applied for the total syntheses of cephalotane diterpenoids

Scheme 25-2. Key strategies applied for the total syntheses of cephalotane diterpenoids

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