Kalmanol是一种从美国南石科细叶野豌豆的叶子中分离得到一种新型的二萜类化合物，跟grayanotoxins家族其他化合物一样，具有提高钠离子渗透性并导致心脏中毒的药理活性。作为grayanotoxins家族中结构最为复杂的化合物，自1989年发现以来一直未见全合成报道。我们希望借鉴其生源物合成机制，采用碳阳离子环化反应构建kalmanol生物合成前体即对映?-贝壳杉烯骨架化合物；然后利用碳阳离子引发的骨架重排反应，将6/6/6/5环系转变为6/7/5/5环系，构建kalmanol的C/D环；最后利用六元A环缩环成五元环，实现5/8/5/5环系的构建。这种骨架重排反应不仅可以完成kalmanol的全合成，还可以建立grayanotoxins 家族中其他天然产物，包括grayanotoxin I、II与III等一系列天然产物。这些仿生合成工作将为该类复杂二萜的合成提供高效的合成路线。

Kalmanol, a new diterpene isolated from the leaves of Kalmia angustifolia L, is pharmacologically active and is cardiotoxic as a consequence of its ability to increase the permeability of sodium ions inexcitable membranes as do the grayanotoxins. Kalmanol is considered as one of the most complex structures among the grayantoxins. There has no report on the total synthesis of kalmanol since its isolation and characterization in 1989. According to the biosynthetic hypothesis, we design a polyene cationic cyclization to achieve the requsite core structure of ent-kaurene, which is proposed as the biosynthesis precusor for kalmanol. The subsequent skeleton rearrangment will convert the 6/6/6/5 ring system into the 6/7/5/5 ring system to ensure the C/D ring of kalmanol. Finally, the six-membered A ring will be contracted to a five-member ring to complete the 5/8/5/5 ring system of kalmanol. With these novel skeleton rearrangements as the key transformations, kalmanol and strcuturally related natural products, such as grayanotoxin I, II and III, can be synthesized. The biomimetic strategy in this proposal not only provides an efficient route to construct theses complex diterpenoids, but also gives insights of the biosynthetic hypothesis of grayanotoxins.