Chen Ming-Hua, Chang Shan-Shan, Dong Biao, Yu Li-Yan, Wu Ye-Xiang, Wang Ren-Zhong, Jiang Wei, Gao Zeng-Ping, Si Shu-Yi
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College Beijing 100050 China
Key Laboratory for Uighur Medicine, Institute of Materia Medica of Xinjiang Urumqi 830004 China.
RSC Adv. 2018 Jan 30;8(10):5138-5144. doi: 10.1039/c7ra13241g. eCollection 2018 Jan 29.
Ahmpatinin Bu (1) and statinin Bu (2), two new linear peptides, a novel pyrrolidine derivative, (-)-()-2-[3-(6-methylheptanamido)-2-oxopyrrolidin-1-yl] acetic acid (3), and three known pepstatin derivatives (4-6) along with their corresponding methanolysis artifacts (7-9) were isolated from sp. CPCC 202950. Their structures were elucidated on the basis of extensive spectroscopic data using Marfey's analysis, chiral-phase HPLC, and ECD and OR calculation to determine the absolute configurations. Compound 1 contains an unusual amino acid, 4-amino-3-hydroxy-5-(4-methoxyphenyl)pentanoic acid (Ahmppa), and 3 is the first natural product with a 2-(3-amino-2-oxopyrrolidin-1-yl)acetic acid system. Compounds 1, 2, and 4-9 are HIV-1 protease inhibitors. In particular, ahmpatinin Bu (1) exhibits significant inhibitory activity against HIV-1 protease with an IC value of 1.79 nM. A preliminary structure-activity relationship is discussed.
从链霉菌属CPCC 202950中分离得到了Ahmpatinin Bu（1）和Statinin Bu（2）这两种新型线性肽、一种新型吡咯烷衍生物（-）-（-）-2-[3-（6-甲基庚酰胺基）-2-氧代吡咯烷-1-基]乙酸（3）以及三种已知的胃蛋白酶抑制剂衍生物（4-6）及其相应的甲醇解产物（7-9）。通过广泛的光谱数据，利用马尔菲分析法、手性相高效液相色谱法以及ECD和OR计算来确定绝对构型，从而阐明了它们的结构。化合物1含有一种不寻常的氨基酸4-氨基-3-羟基-5-（4-甲氧基苯基）戊酸（Ahmppa），化合物3是首个具有2-（3-氨基-2-氧代吡咯烷-1-基）乙酸系统的天然产物。化合物1、2以及4-9均为HIV-1蛋白酶抑制剂。特别是，Ahmpatinin Bu（1）对HIV-1蛋白酶表现出显著的抑制活性，其IC值为1.79 nM。文中还讨论了初步的构效关系。
