Enantioselective preparation and enzymatic cleavage of spiroisoxazoline amides

Several enantiopure spiroisoxazoline amides were prepared from tert-butyles ter 22, which is obtained via an enantiotopic groups differentiating high p ressure Diels-Alder cycloaddition. Treatment of these amides with an isoxaz oline-splitting enzyme, which is involved in an injury induced defense reac tion of the sponge Aplysina cauliformis, proves the bromoatoms in the cyclo hexenone moiety to be important for enzyme binding, while the presence of t he N-H bond of a monoalkylamide turned our to be mandatory for ring fission . The pertinence of these results to the ring splitting mechanism is discus sed. (C) 2000 Elsevier Science Ltd. All rights reserved.