Département de Chimie and PROTEO, Université Laval, Québec, G1V 0A6, Canada.
Centre de recherche du CHU de Québec-Université Laval, Département de Microbiologie-Infectiologie et d'Immunologie, Université Laval, Québec, G1 V 0A6, Canada.
J Nat Prod. 2020 Jun 26;83(6):1778-1783. doi: 10.1021/acs.jnatprod.9b00936. Epub 2020 Jun 2.
Dominicin, a macrocyclic peptide isolated from the marine sponge , 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/OBu biorthogonal protection strategy on oxime resin to facilitate concomitant -terminal and side-chain -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
道宁定，一种从海洋海绵中分离出来的大环肽，已通过固相肽合成首次被合成。该策略使用肟树脂，并利用肟酯键的亲核敏感性。该合成依赖于线性前体的制备，然后进行树脂上的头到尾伴随环化-裂解。这是首次报道在肟树脂上使用 Boc/OBu 双正交保护策略来促进未保护肽的伴随 -末端和侧链 -丁醚脱保护环化。此外，我们还报告了道宁定的首次抗疟研究。有趣的是，天然大环肽对氯喹-甲氟喹-乙胺嘧啶耐药的 Dd2 株表现出有效的低微摩尔活性（1.8 μM）。
