Total synthesis and cytotoxicity evaluation of the spirostanol saponin gitonin.

ABSTRACT

The spirostanol saponin gitonin was efficiently synthesized in 12 steps (longest linear sequence) in 18.5% overall yield from the commercially available isopropyl ß-D-1-thiogalactopyranoside (IPTG) and tigogenin. A cascade two-step glycosylation and Schmidt's inverse procedure significantly facilitated the synthesis of gitonin and its derivatives. The cytotoxic activities of gitonin and its structural analogues were evaluated against A549, HepG2, and MCF-7, and most of them exhibited moderate to excellent inhibitory activity. Our study demonstrates that the removal of the ß-D-galactopyranosyl residue (attached at C-2 of the glucose unit) from gitonin would not decrease the inhibition activities; however, further cleavage of sugar units could seriously reduce the activities. A bioassay on these cancer cell lines also suggested that the presence of 2α-hydroxy on the aglycone weakened the cytotoxicity of the designed saponin.