Synthesis and cytotoxicity of (-)-homo-renieramycin G and its derivatives

(-)-Homo-renieramycin G and its twenty derivatives were prepared from l-tyrosine methyl ester via a multi-step route. Their cytotoxicities were tested against four human cancer cell lines (A549, HeLa, KB and BGC-823). (-)-Renieramycin G and (-)-homo-renieramycin G showed comparable cytotoxicity against these four cancer cell lines, which indicated that the expansion of ring C from the six-membered 1,4-piperazinone to the seven-membered 1,4-diazepanone had no obvious impact on the cytotoxicity. Compound 42 with methyl side chain and compounds 38-41 with heterocyclic aromatic side chains at C-23 exhibited the most potent cytotoxicity with the IC₅₀ values at the level of 10^-6 M.