瑞香烷型二萜天然产物的合成进展

Synthetic Progress of Daphnane-type Diterpenoids

瑞香烷型二萜类天然产物拥有5/7/6三环骨架的复杂分子结构,含有多个手性中心,通常在C3、C4、C5、C9、C13、C14、C20等位置含有手性羟基;其中,诸多化合物在C9、C13、C14位置的手性羟基之间形成特定的原酸酯结构.该类天然产物在抗HIV、抗癌、抗白血病、亲神经性、杀虫、细胞毒性等方面显示显著的生物活性.瑞香烷型的密集的高氧化数的多环骨架和其引人注目的生物活性吸引了众多研究者的合成兴趣,尽管迄今为止成功的全合成报道依然鲜见,但合成化学家对其多环骨架的构建已发展了大量有益的策略和方法,在此对相关合成工作进行归纳综述.

Daphnane diterpenoids usually embrace a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C3, C4, C5, C9, C13, C14, C20 and some special ones have a characteristic orthoester motif located at C9, C13, C14. The daphnane diterpenoids can be categorized into daphnetoxins, 12-hydroxydaphnetoxins, 1-alkyldaphnanes, resiniferonoids, genkwanines and rediocides, based on the oxygen containing functions at rings B and C, as well as the substitution pattern of the ring A. Besides, some daphniphyllum alkaloids are qualified with daphnane and seco-daphnane skeletons. Up to now, more than 100 daphnane diterpenoids have been isolated from Thymelaeaceae and Euphorbiaceae. Their structures have been determined on the basis of chemical correlation, NMR, X-ray diffraction, IR and other spectral analysis. The in-vitro and in-vivo experiments of these compounds have shown that they bear a wide range of biological activities including anti-HIV, anticancer, anti-leukemic, neurotrophic, pesticidal and cytotoxic effects. The biogenic hypothesis postulated that the daphnane-type and the tigliane type diterpenoids can be derived from a common intermediate, and that the tigliane-type can be transferred into the daphnane-type diterpenoids. There have been few papers on the total syntheses of daphnane diterpenoids owing to the synthetic challenges derived from their dense, highly oxygenated and polycyclic skeletons. However, numerous synthetic endeavors have been made in constructing core structures of daphnane diterpenoids based on various methodologies. In this paper, we focus on reviewing the synthetic efforts which have been made for daphnane diterpenoids, and we divide the main body of this paper into two parts, total syntheses and the related methodologies. The first part contains the asymmetric total synthesis of（＋）-resiniferatoxin, the gateway synthesis of C6-C7-epi-yuanhuapin, and the biomimetic synthesis of（±）-methyl-homosecodaphniphyllate. The second part is classified according to the sequence of constructing the ABC core of daphnane diterpenoids, including the [X-BC-ABC] approach, the [X-AB-ABC] approach, the [AX-ABC] approach, the [CX-ABC] approach, the [A＇B＇C＇-ABC] approach and the [X-ABC] approach.