2-nitro and 4-nitro-quinone-methides are not irreversible inhibitors of bovine beta-glucuronidase

4-Benzylamino-(and 4-chloromethyl)-2-nitro-beta -D-glucuronides (4, 10) and their 2-substituted-4-nitro regioisomers (7, 13) were prepared by glycosid ation of the 3-nitro-4-hydroxy- and the 2-hydroxy-5-nitro-benzylic alcohol, respectively, with a glucuronyl donor. Carbonate activation followed by re action with benzylamine or methanesulfonyl chloride afforded, after complet e deprotection, the target molecules 4, 7, 10 and 13. These compounds have been synthesized to determine whether these molecules are (or not) glucuron idase inhibitors. After incubation with bovine liver beta -glucuronidase, n one of the cleavage products (the titled quinone-methides) showed to be irr eversible inhibitors of this enzyme. (C) 2001 Published by Elsevier Science Ltd.