Chemical Synthesis of marine pyrrole alkaloids effective against multidrug-resistant cancers

我们开发了一种合成3,4-二芳基吡咯型海洋生物碱的有效方法，该生物碱具有抗多药耐药（MDR）癌细胞的细胞毒活性。n -烷基二乙酸酯与草酸二甲酯的hinsberg型缩合反应生成n -烷基-3,4-二羟基吡咯-2,5-二羧酸酯。在Pd(0)催化剂的作用下，将3,4-二羟基吡咯的双酸酯衍生物与多种芳基硼酸交叉偶联，得到产率高的3,4-二烷基吡咯-2,5-二羧酸酯。在3位和4位上逐步引入不同的芳基是可行的。这些方法成功地应用于片层素G、三甲基醚、片层素D、L和n的全合成，并实现了过甲基storniamide A和ningalin B的正式合成。

We have developed an efficient procedure for the synthesis of 3,4-diarylpyrrole-type marine alkaloids, which exhibit cytotoxic activity against multidrug-resistant(MDR) cancer cells.Hinsberg-type condensation of N-alkyliminodiacetates with dimethyl oxalate produced N-alkyl-3,4-dihydroxypyrrole-2,5-dicarboxylates. The bistriflate derivatives of the 3,4-dihydroxypyrroles were cross-coupled with a wide range of arylboronic acids in the presence of Pd(0) catalysts to give the 3,4-diarylpyrrole-2,5-dicarboxylates in excellent yields. The stepwise introduction of different aryl groups at the 3- and 4-positions was found to be feasible. These procedures were successfully applied for the total syntheses of lamellarin G trimethyl ether, lamellarins D,L,and N. Formal syntheses of permethyl storniamide A and ningalin B were also achieved.