Saframycin A

沙弗拉霉素 AChemical Name: N-[(6S,7R,9R,14aS,15R)-7-Cyano-1,5,6,7,9,10,13,14,14a,15-decahydro-2,11-dimethoxy-3,12,16-trimethyl-1,4,10,13-tetraoxo-6,15-imino-4H-isoquino[3,2-b][3]benzazocin-9-ylmethyl]-2-oxopropanamide
CAS No. 66082-27-7
项目整合开发状态: Preclinical
项目研究机构: Chiba University (Originator)
合成路线: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.