Total synthesis and cytotoxicity of haterumalides NA and B and their artificial analogues.
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.
Ueda
Mitsuru
M
Department of Chemistry, Graduate School of Pure and Applied Sciences, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8571, Japan.
Yamaura
Masashi
M
Ikeda
Yoichi
Y
Suzuki
Yuta
Y
Yoshizato
Kensaku
K
Hayakawa
Ichiro
I
Kigoshi
Hideo
H