Reniochalistatin E (1) is one of the five related cyclic peptides isolated from the marine sponge Reniochalina stalagmitis. The discovery of these compounds resulted from a screening program directed toward the identification of proline-rich bioactive compounds. Reniochalistatin E is the only member of the family to possess a tryptophan amino acid residue. Given the cytotoxicity observed for 1, efforts were directed toward developing a synthetic route to 1. The first total synthesis of 1 has been accomplished in a 15-step route in an overall 5.0% yield. The synthetic sample of reniochalistatin E was shown to have similar activity toward HeLa and RPMI-8226 cell lines compared to the natural sample, with IC₅₀ values of 16.9 vs 17.3 μM and 4.5 vs 4.9 μM, respectively. Interestingly, both of the fully deprotected octapeptides constructed toward the synthesis of reniochalistatin E were shown to have cytotoxicity. The route provides a means to probe the structure–activity relationship of 1 and further biological investigations.

中文翻译：

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肾上腺素E的全合成

Reniochalistatin E（1）是从海洋海绵Reniochalina stalagmitis分离的五个相关环肽之一。这些化合物的发现源于针对富含脯氨酸的生物活性化合物的鉴定的筛选程序。Reniochalistatin E是家族中唯一拥有色氨酸氨基酸残基的成员。鉴于观察到的1的细胞毒性，人们致力于开发合成1的途径。的第一全合成1已经在15步路线在一个整体5.0％的收率完成。结果显示，与天然样品相比，肾上腺素甲壳素E的合成样品对HeLa和RPMI-8226细胞系具有相似的活性_50个值分别为16.9 vs 17.3μM和4.5 vs 4.9μM。有趣的是，两个合成的完全去保护的八肽都被合成为具有神经毒性的，它们都具有细胞毒性。该途径提供了一种手段来探究1与进一步生物学研究的结构与活性之间的关系。