Total synthesis and bioactivity of the marine alkaloid pityriacitrin and some of its derivatives

We report herein the chemical synthesis and biological evaluation of β-carboline alkaloid pityriacitrin and some of its new derivatives. Using tryptophan or 5-hydroxytryptophan and 5-substituted indole-3-glyoxals as the starting materials, pityriacitrin and some of its derivatives were synthesized via the acid-catalyzed Pictet–Spengler reaction and fully characterized by 1H and 13C NMR, mass spectroscopy and IR determinations. Biological studies revealed that pityriacitrin has a weak antiproliferative activity against a panel of breast and prostate cancer cell lines, whereas some of its derivatives exhibited stronger and potent activity, which was associated with induction of both cell apoptosis and necrosis.

Marine alkaloids Pityriacitrin and Pityriacitrin B were totally synthesized. New series of derivatives were obtained by modification. Some of the derivatives exhibited stronger anticancer activity comparing with Pityriacitrin.Figure optionsDownload as PowerPoint slideHighlights
► synthesis of β-carboline alkaloid pityriacitrin and its new derivatives.
► Acid-catalyzed Pictet–Spengler reaction was introduced during the reaction.
► Some derivatives compounds were found to have stronger antiproliferative activity.