Synthesis and bioactivity of bis-steroidal pyrazine 23-deoxy-25-epi ritterostatin G1.

Cephalostatins, ritterazines and their hybrid bis-steroidal pyrazine analogs such as 25-epi-rittereostatin G1 show unusually high potency against a wide range of cancer cell lines. Herein, we report the synthesis and bioactivity of 23-deoxy-25-epi ritterostatin G1, which lacks the 23-hydroxyl group of 25-epi rittereostatin G1. The less oxygenated bis-steroidal pyrazine was ∼50- to 1000-fold less potent than 25-epi ritterostatin G1, highlighting the importance of the 23-hydroxyl group for the antiproliferative activity of the cephalostatin/ritterazine class of drugs.