The unusual ability of α-angelicalactone to form adducts:: A kinetic approach

Since alpha-angelicalactone (AAL) substantially inhibits the formation of tumors, here its chemical reactivity was compared with that of carcinogenic lactones. Investigation of the electrophilic potential of AAL was carried out by studying the capacity of this lactone to form adducts with NBP, 4-(p-nitrobenzyl)pyridine, a substrate with nucleophilic characteristics similar to DNA bases. The formation of the AAL-NBP adduct occurs about 900,000-fold faster than with beta-propiolactone, the most effective carcinogenic lactone (Delta G(35)(#) = 52 and 87 kJ mol(-1), respectively). A stopped-flow technique was required for this reaction to be monitored. It was concluded that the formation of AAL-NBP adducts takes place through an entropy-strain-catalyzed mechanism caused by early lactone ring cleavage. The kinetic results are consistent with the AAL potential as a chemoprotective agent. (C) 2007 Wiley Periodicals, Inc.