A detailed overview is presented of recent total synthesis approaches to four different diterpenoids--the ginkgolides, tonantzitlolone, ingenol and eleutherobin. Due to their structural complexity, all pose major challenges for total synthesis, guaranteeing diverse strategic tours de force and a rich synthetic chemistry. Additionally, all four diterpenoids are of major relevance because of their biological (target) or pharmaceutical properties.

The total synthesis of the cyclic diterpene ent-tonantzitlolone (ent-1) is presented. Key steps for assembling the macrocyclic core structure of 1 are a highly selective aldol reaction and an E selective ring-closing metathesis reaction. A detailed investigation of these two steps and the final transformations towards the completion of the synthesis is disclosed.

When an 2-isopropoxy-substituted benzylidene ligand of a Hoveyda-type Ru-metathesis complex is modified by an additional 4-diethylamino group and treated wit PTSA it yields a highly active precatalyst suitable for RCM, cross metathesis, and enyne metathesis. The important property of this ammonium tagged Rucomplex is associated with the possibility of its easy removal by a simple filtration protocol.During recent years, olefin metathesis using modern ruthenium catalysts has become a key reaction in organic chemistry. 1 A principal problem for applications outside academic laboratories is associated with heavy-metal impurities in the products and their efficient removal. 2 Ruthenium hydride complexes, formed after decomposition of metathesis catalysts can also lead to unwanted side reactions during product isolation and purification. 3 Several protocols such as scavengers, biphasic extraction, and silica gel chromatography have been proposed to overcome these problems. Another strategy to make Ru-based olefin-metathesis technology more economical is the immobilisation of these homogeneous catalysts on a solid phase or in ionic liquids. 4 We demonstrated that the 5-and 4-nitro-substituted complexes 6a,b (Figure 1) initiate olefin metathesis dramatically faster than the parent Hoveyda-Grubbs catalyst 3b. 5 We proposed that the electron-withdrawing group (EWG) in the benzylidene fragment of 6 decreases the electron density on the chelating oxygen of the isopropoxy group and weakens the O→Ru coordination, facilitating faster initiation of the catalytic cycle.In accordance with this assumption, we observed that complex 7 (Scheme 1), bearing the electron-donating (EDG) diethyl amino group shows low or no activity in olefin metathesis. 6a However, in a striking contrast, quaternisation of the nitrogen atom either by alkylation or protonation leads to ammonium cations with electronwithdrawing properties, such as 8 and 10. Both these salts show excellent activity, surpassing the parent HoveydaGrubbs complex 3b in terms of initiation speed. 6a,b In addition, the conversion of the Et 2 N group into polar quaternary ammonium salt, yielded the resulting catalyst 8 (R = Me, X = I), is suitable for applications in aqueous solvents. 7 Unfortunately, quaternisation of 7 with MeI or

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The synthesis of the diterpene (+)-tonantzitlolone A and a series of derivatives is reported. The study includes the determination of their antiproliferative activities against selected cancer cell lines.