Synthesis and biological evaluation of spongistatin/altohyrtin analogues: E-ring dehydration and C46 side-chain truncation.


Simplified analogs of the potent antimitotic marine macrolide spongistatin 1/altohyrtin A were synthesized and evaluated as growth inhibitory agents against a range of human tumor cell lines, including Taxol-resistant strains, revealing that E-ring dehydration leads to enhanced cytotoxicity at the low picomolar level while truncation of the side-chain at C46 results in a drastic decrease in activity.

Chemical Communications (Cambridge, United Kingdom)