Synthesis and biological activities of hapalosin derivatives with modification at the C12 position

Among the hapalosin derivatives synthesized, the compounds carrying methyl (Figure 2 and Scheme 1), methylthioethyl ( Figure 2 and Scheme 1) and phenylmethyl ( Figure 2 and Scheme 1) groups at the C12 position possess only the cis-peptide structure, in contrast to the cases of Figure 2 and Scheme 1 and Figure 2 and Scheme 1. In addition to their conformational stability, the biological activities of the compounds were determined in relation of the P-glycoprotein-mediated MDR-reversing activity and induction of apoptosis.