Synthesis and bioactivity of bis-steroidal pyrazine 23-deoxy-25-epi ritterostatin GN1N

- Synthesis of ritterostatin, a hybrid analog of ritterazine and cephalostatin.
- Ritterostatin synthesis involves reductive/oxidative modifications of hecogenin acetate.
- Evaluation of the impact of C23 hydroxyl group on bioactivity of ritterostatin.

Cephalostatins, ritterazines and their hybrid bis-steroidal pyrazine analogs such as 25-epi-rittereostatin GN1N 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 GN1N, which lacks the 23-hydroxyl group of 25-epi rittereostatin GN1N. The less oxygenated bis-steroidal pyrazine was ∼50- to 1000-fold less potent than 25-epi ritterostatin GN1N, highlighting the importance of the 23-hydroxyl group for the antiproliferative activity of the cephalostatin/ritterazine class of drugs.

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