School of Chemistry, University of Hyderabad, C. R. Rao Road, Gachibowli, Hyderabad - 500 046, India.
Org Biomol Chem. 2023 Jul 19;21(28):5861-5865. doi: 10.1039/d3ob00922j.
Total synthesis of the marine natural product bengamide E and 5--bengamide E has been accomplished using two routes: (i) a polyhydroxy acid precursor involving a total of 16 steps with an overall yield of 17.0% and (ii) a cyclic lactone precursor with a total of 12 steps and overall 23.0% yield. The key steps involve (1) regioselective -methoxybenzylidine ring opening, (2) a stereoselective Grignard reaction and (3) olefin cross-metathesis. The total synthesis could provide significant quantities of bengamide E and 5--bengamide E as all the reaction processes were very efficient and the raw materials were inexpensive and highly abundant. The protocol has an advantage over previously reported methods as it provides ready access to the C-5 hydroxy group for further modification and its future structure-activity relationship studies for anti-tumor activity.
已通过两种途径实现海洋天然产物苯并酰胺 E 和 5--苯并酰胺 E 的全合成：（i）总共 16 步的多羟基酸前体，总收率为 17.0%；（ii）总共 12 步的环状内酯前体，总收率为 23.0%。关键步骤包括：（1）区域选择性 -甲氧基苯亚甲基环开裂，（2）立体选择性格氏反应和（3）烯烃交叉复分解。该全合成方法可以提供大量的苯并酰胺 E 和 5--苯并酰胺 E，因为所有反应过程都非常高效，且原料便宜且丰富。与以前报道的方法相比，该方案具有优势，因为它可以方便地获得 C-5 羟基，用于进一步修饰和未来的抗肿瘤活性构效关系研究。
