STEREOSELECTIVE SYNTHESIS OF (2S,3S)-NORSTATINE DERIVATIVES BY ADDITION OF LITHIATED METHOXYALLENE TO AMINO ALDEHYDES AND SUBSEQUENT OZONOLYSIS

Addition of lithiated methoxyallene 2 to optically active N-benzyl-Boc -protected amino aldehydes 12-14 and to aldehyde 16 provides products 17-20 with good to excellent diastereoselectivity. These adducts are s ubsequently cleaved by ozonolysis to give alpha-hydroxy-beta-amino aci d derivatives 21-25 in good overall yield. By conversion into an oxazo lidone derivative, the configuration of the major diastereomer was det ermined to be anti (2S,3S). Thus, the additions of 2 follow the course proposed by the Felkin-Anh model and are not ruled by chelation effec ts. The diastereoselective synthesis of 22 constitutes one of the simp lest routes to a protected norstatine derivative.