The total synthesis of haterumalides NA and B, potent cytotoxic marine macrolides, was achieved by using B-alkyl Suzuki-Miyaura coupling and Nozaki-Hiyama-Kishi coupling as key steps. Compared to our first-generation approach for ent-haterumalide NA methyl ester, this second-generation synthesis yielded much more of the key intermediate. This synthesis established the relative stereochemistry of haterumalide B. Furthermore, the structure-cytotoxicity relationships of haterumalides were investigated. The combination of macrolide and side chain parts proved to be important to the cytotoxicity.

Second-generation total synthesis of haterumalide NA, a potent cytotoxic marine macrolide, was achieved by using B-alkyl Suzuki-Miyaura coupling and Nozaki-Hiyama-Kishi coupling as key steps (1.2% in 33 steps). Compared to our first-generation approach, the second-generation synthesis is much improved in the yield of key intermediate.

The first total synthesis of the enantiomer of jolkinolide D, a bioactive diterpene from Euphorbia jolkini Boiss, was achieved from abietic acid. The enantiomer did not exhibit the biological activities that the natural jolkinolide D possesses.

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