An expedient total synthesis of ent-(−)-7-deoxy-trans-dihydronarciclasine

A short and efficient stereoselective total synthesis of (−)-7-deoxy-trans-dihydronarciclasine, an ent-form of a highly potent antineoplastic agent constituent of the Amaryllidaceae alkaloids, is described. Starting from the enantiopure form of a known arylcyclohexylamine type precursor 6, which was synthesized enantioselectively utilizing a highly enantioselective nitromethane addition, the three hydroxy groups on the C-ring with the required stereochemistry were introduced by a chemo- and stereoselective enone reduction (NaBH4/CaCl2 system) followed by a Mitsunobu reaction and subsequent osmylation. The ring closure of the B-ring was accomplished by the Banwell modification of the Bischler–Napieralski reaction.