Synthesis and anticancer activity of side chain analogs of the crambescidin alkaloids

Twenty three side chain analogs of the crambescidin alkaloids were prepared from the corresponding pentacyclic zwitterionic core acid. In the crambescidin 800 and 657 series, potency increased with increasing chain length. In addition, substantial variations in tumor selectivity with structure were seen. Crambescidin analogs having short, nonpolar side chains were identified for the first time as promising anticancer agents.