ENANTIOSELECTIVE SYNTHESIS OF 5-LO INHIBITOR HYDROXYUREAS - TANDEM NUCLEOPHILIC ADDITION-INTRAMOLECULAR CYCLIZATION OF CHIRAL NITRONES

An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygena se inhibitors is reported via a five-step sequence in about 39% overal l yield. The synthesis is based on a novel tandem nucleophilic additio n-intramolecular cyclization reaction in which a chiral nitrone functi ons as the electrophilic acceptor species. A mannose-based chiral auxi liary controls the diastereoselectivity of the reaction in an 8:1 rati o. After the auxiliary removal and appropriate functionalization, a si ngle recrystallization afforded the target structures in > 99% ee.