Synthesis and evaluation of the cytotoxicity of apoptolidinones A and D.
AUTHORS
Ghidu
VPVictor P ,
Wang
J Jingqi ,
Wu
B Bin ,
Liu
Q Qingsong ,
Jacobs
A Aaron ,
Marnett
LJ Lawrence J ,
Sulikowski
GA Gary A .
The Journal of organic chemistry. 2008 7 4; 73(13).
4949-55
- PMID: 18543990[PubMed].
- PMCID: PMC2572754.
- NIHMSID: NIHMS72310
ABSTRACT
Apoptolidins A-D are microbial secondary metabolites shown to be selectively cytotoxic against several cancer cell lines and noncytotoxic against normal cells. Total syntheses of apoptolidinones A and D are reported. The efficient synthetic strategy leading to the apoptolidinones features construction of the common 20-membered macrolactone by an intramolecular Suzuki reaction and stereocontrolled aldol reactions establishing the C19/C20 and C22/C23 stereocenters. In contrast to apoptolidin A, the aglycones apoptolidinone A and D were shown to be noncytotoxic when evaluated against human lung cancer cells (H292).