Portal de Periódicos da CAPES

Total Synthesis and Cytotoxicity of Haterumalides NA and B and Their Artificial Analogues

2009; American Chemical Society; Volume: 74; Issue: 9 Linguagem: Inglês

10.1021/jo802806z

1520-6904

Mitsuru Ueda, Masashi Yamaura, Yoichi Ikeda, Yuta Suzuki, Kensaku Yoshizato, Ichiro Hayakawa, Hideo Kigoshi,

Catalytic Cross-Coupling Reactions

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.