Dominicin, a macrocyclic peptide isolated from the marine sponge Eurypon laughlini, has been synthesized for the first time by solid-phase peptide synthesis. The strategy uses oxime resin and takes advantage of the nucleophile susceptibility of the oxime ester bond. The synthesis relies on the preparation of a linear precursor followed by on-resin head-to-tail concomitant cyclization–cleavage. This is the first report of the use of a Boc/O^tBu biorthogonal protection strategy on oxime resin to facilitate concomitant N-terminal and side-chain tert-butyl ether deprotection cyclization of unprotected peptides. Also, we report the first antimalarial investigation of dominicin. Interestingly, the natural macrocyclic peptide demonstrates effective low micromolar activity (1.8 μM) against the chloroquine-mefloquine-pyrimethamine-resistant Dd2 strain of Plasmodium falciparum.

中文翻译：

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来自海洋海绵的环状八肽 Dominicin 的总合成和抗疟活性。

Dominicin 是一种从海洋海绵Eurypon laglini 中分离出来的大环肽，首次通过固相肽合成法合成。该策略使用肟树脂并利用肟酯键的亲核敏感性。合成依赖于线性前体的制备，然后在树脂上进行头对尾伴随的环化-裂解。这是在肟树脂上使用 Boc/O ^t Bu 双正交保护策略以促进伴随的N端和侧链叔的第一份报告未保护肽的-丁基醚去保护环化。此外，我们还报告了多米尼克星的首次抗疟研究。有趣的是，天然大环肽对恶性疟原虫的氯喹-甲氟喹-乙胺嘧啶抗性 Dd2 菌株表现出有效的低微摩尔活性 (1.8 μM) 。