A stereocontrolled synthesis of (-)-saframycin A has been described: The condensation of the optically active alpha-aminoaldehydes (I, N-protected) and (II, C-protected) in dichloromethane in the presence of sodium sulfate provides the imine (III), which by a treatment with LiBr in dimethoxy-ethane yields the isoquinoline (IV). Methylation of (IV) with formaldehyde and NaBH(OAc)3 in acetonitrile, followed by double deprotection, first of the hydroxy group with TBAF/AcOH in THF and then of the amino group with DBU in dichloromethane, affords the N-methylated compound (V), which is cyclized with the protected 2-aminoacetaldehyde (VI) in dichloromethane in the presence of sodium sulfate giving the bis(tetrahydoisoquinoline) compound (VII). A new cyclization reaction of (VII) in the presence of ZnCl2 and trimethylsilyl cyanide in 2,2,2-trifluoroethanol/THF yields the pentacyclic compound (VIII), which by deprotection of the amine group with DBU in dichloromethane and condensation with 2-oxopropionyl chloride (IX) by means of N,N-diethylaniline in dichloromethane affords compound (X). Finally, this compound is submitted to oxidative demethylation of the hydroquinones with iodosobenzene in acetonitrile/water to give (-)-saframycin A.