Synthesis and biological evaluation of a potent salicylihalamide A lactam analogue
作者:Dan Balan、Christopher J. Burns、Nicholas G. Fisk、Helmut Hügel、David C. S. Huang、David Segal、Charlotte White、Jörg Wagler、Mark A. Rizzacasa
DOI:10.1039/c2ob26649k
日期:——
The first synthesis of a lactam analogue 3 of salicylihalamide A (1) is reported. A key step in the approach was a photochemical acylation coupling between amine 10 and dioxinone 9 to form the amide 19. Acetylation followed by RCM with Grubbs 1st generation catalyst gave the desired E-lactam 23 (E : Z ratio 87 : 13) as the major compound. Conversion of macrolactam 23 into the vinyl iodide 26 followed by Cu catalysed cross coupling with the diene amide 7 gave aza-salicylihalamide analogue 3 in good yield. This compound demonstrated potent activity against several human leukaemia cell lines.
首次合成了水杨酸氟代胺A(1)的乳酰胺类似物3。该方法中的一个关键步骤是胺10与二恶烯酮9之间的光化学酰基化偶联,形成酰胺19。随后进行的醋酰化和使用Grubbs第一代催化剂的RCM反应,得到了目标的E-乳酰胺23(E : Z比率为87 : 13)作为主要化合物。将大环乳酰胺23转化为乙烯基碘化物26,随后与二烯酰胺7进行铜催化的交叉偶联,良好地得到氮取代水杨酸氟代胺类似物3。该化合物对多个人类白血病细胞系表现出强效活性。