Abstract
Haterumalides, isolated from Okinawan marine animals, are 14-membered macrolides with strong cytotoxicity against human cancer cell lines. We have achieved the total synthesis of haterumalides NA and B by using B-alkyl Suzuki-Miyaura coupling and Nozaki-HiyamaKishi coupling as key steps. Compared to our first-generation approach for ent-haterumalide NA methyl ester, this second-generation synthesis yielded the key intermediate in much better yield. This synthesis also 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 strong cytotoxicity.
Original language | English |
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Pages (from-to) | 814-823 |
Number of pages | 10 |
Journal | Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry |
Volume | 68 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 1 2010 |
Externally published | Yes |
Keywords
- Biselides
- Haterumalides
- Marine cytotoxic macrolides
- Structure-cytotoxicity relationships
- Total synthesis
ASJC Scopus subject areas
- Organic Chemistry