Cdc25A Protein phosphatase inhibitors from anomalous ozonolysis of 5,6-seco-5-oxo-3-cholesten-6-oic acid

Ozonolysis of the α,β-unsaturated keto acid, 5,6-seco-5-oxo-3-cholesten-6-oic acid (1), in ethyl acetate/acetic acid/water (15:15:1) at −20°C, followed by addition of piperidine, led to several novel lactone products (2–6), presumably formed through rearrangements of ozonide intermediates. The major product 2 was a lactone containing a dioxolane-4-one moiety, which exhibited a carbonyl stretching frequency at 1815 cm−1. Three of the five products resulted from loss of two carbon atoms from the starting material rather than one carbon atom as commonly observed in the ‘anomalous ozonolysis’ of α,β-unsaturated ketones. Some of these compounds possess moderate inhibitory activities against human Cdc25A protein phosphatase, an enzyme overexpressed in several human tumor cell lines.