Synthesis and biological evaluation of 20-hydroxytriptonide and its analogues

20-Hydroxytriptonide was synthesized from readily accessible l-abietic acid in 22 linear steps, which features a Barton reaction carried out under air atmosphere to install the C20-hydroxy group. Meanwhile, we also synthesized (5R)-5-hydroxytriptolide's probable metabolite product. Preliminary structure–activity relationship studies revealed that C20-angular methyl group might play a key role in maintaining the electronic properties of the whole molecule, which was essential for retaining the cytotoxic activity and might easily and inevitably be affected by the introduction of a new group.