Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, As Lagoas/Marcosende, 36310 Vigo, Spain.
Chemistry. 2009 Sep 28;15(38):9928-37. doi: 10.1002/chem.200901056.
Homo- and heterodimeric bispyrrolidinoindoline diketopiperazine alkaloids have been synthesized following a concise, versatile, and stereoselective route. Highlights of the sequence are a diastereoselective construction of the C3a-bromo-hexahydropyrrolo[2,3-b]indole nucleus, its Co(I)-induced C3a-C3a' dimerization, and the twofold or sequential amide-bond formation before cyclization to the diketopiperazine of the homo- or heterodimeric alkaloids, respectively. Stereochemical diversity is achieved through the choice of the appropriate amino acids combined with the base-induced epimerization of the C2-acyl-hexahydropyrrolo[2,3-b]indole at C2. According to this strategy, the natural products (+)-WIN 64821 1, (+)-WIN 64745 2 and (+)-asperdimin 6 as well as analogues (5, 22, 32, 44) with different relative and absolute configuration have been efficiently synthesized. The flexibility of this synthetic methodology has facilitated the structural revision of the natural product (+)-asperdimin, whose structure has been corrected to diastereomer 6.
已经通过一种简洁、通用和立体选择性的方法合成了同型和异型双吡咯并吲哚啉二酮哌嗪生物碱。该序列的重点是立体选择性构建 C3a-溴-六氢吡咯并[2,3-b]吲哚核，其 Co(I)诱导的 C3a-C3a'二聚化，以及在分别环化成同型或异型二聚体生物碱的二酮哌嗪之前的两次或顺序酰胺键形成。通过选择合适的氨基酸并结合碱诱导 C2-酰基-六氢吡咯并[2,3-b]吲哚在 C2 处的差向异构化，可以实现立体化学多样性。根据该策略，已经有效地合成了天然产物（+）-WIN 64821 1、（+）-WIN 64745 2 和（+）-asperdimin 6 以及具有不同相对和绝对构型的类似物（5、22、32、44）。这种合成方法的灵活性促进了天然产物（+）-asperdimin 的结构修订，其结构已被修正为非对映异构体 6。
