Indole 2,5-diketopiperazines (DKPs) are an important type of metabolic cyclic dipeptides containing a tryptophan (Trp) unit possessing a range of interesting biological activities. The intriguing structural features and divergent activities have stimulated tremendous efforts towards their efficient synthesis. Herein, we report the development of a unified strategy for the synthesis of three Trp-containing DKPs, namely tryprostatin A, and maremycins A and B, via a sequential C–H activation strategy. The key Trp skeletons were synthesized from the inexpensive, readily available alanine via a Pd(II)-catalyzed β-methyl C(sp³)–H monoarylation. A subsequent C2-selective prenylation of the resulting 6-OMe-Trp by Pd/norbornene-promoted C–H activation led to the total synthesis of tryprostatin A in 12 linear steps from alanine with 25% overall yield. Meanwhile, total syntheses of maremycins A and B were successfully accomplished using a sequential Pd-catalyzed methylene C(sp³)–H methylation as the key step in 15 linear steps from alanine.

中文翻译：

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通过连续 C-H 激活合成含有色氨酸的 2,5-二酮哌嗪：色氨酸 A、马雷霉素 A 和 B 的全合成

吲哚 2,5-二酮哌嗪 (DKP) 是一种重要的代谢环二肽，含有色氨酸 (Trp) 单元，具有一系列有趣的生物活性。有趣的结构特征和不同的活动激发了对其有效合成的巨大努力。在此，我们报告了通过连续 C-H 激活策略合成三种含 Trp 的 DKP，即胰前列腺素 A 和马雷霉素 A 和 B 的统一策略的开发。关键的色氨酸骨架是通过Pd( II ) 催化的 β-甲基 C(sp ³)–H 单芳基化。随后通过 Pd/降冰片烯促进的 C-H 活化对所得 6-OMe-Trp 进行 C2 选择性异戊二烯化，导致在 12 个线性步骤中从丙氨酸全合成胰前列腺素 A，总产率为 25%。同时，使用连续 Pd 催化的亚甲基 C(sp ³ )-H 甲基化作为来自丙氨酸的 15 个线性步骤中的关键步骤，成功地完成了马雷霉素 A 和 B 的全合成。