(-)-15-deoxyspergualin: A new and efficient enantioselective synthesis which allows the definitive assignment of the absolute configuration

(+/-)-15-Deoxyspergualin (DSG) has recently been marketed in Japan for the control of corticoresistant acute renal graft, rejection. A nine-step total synthesis of its eutomer ((-)-DSG) 2 has been developed starting from 7-bromoheptanenitrile 3 and N-1, N-4-bis(benzyloxycarbonyl)spermidine. The use of a chiral alpha-alkylbenzyl group to protect the hydroxyl of the alpha-hydroxyglycine moiety allowed its chromatographic resolution and afforded a practical access to 2 with a high optical purity and a 7% overall yield. Moreover, X-ray structure analysis of the key crystalline intermediate 7b definitely confirmed the previously proposed absolute configuration of 2.