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

Ozonolysis of the alpha,beta -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 degreesC, 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 alpha,beta -unsaturated ketones. Some of these compounds possess moderate inhibitory activities against human Cdc25A protein phosphatase, an enzyme overexpressed in several human tumor cell lines. (C) 2001 Elsevier Science Ltd. All rights reserved.