Ahmpatinin Bu-i, a new HIV-1 protease inhibitor, from Streptomyces sp CPCC 202950

Ahmpatinin Bu-i (1) and statinin Bu-i (2), two new linear peptides, a novel pyrrolidine derivative, (-)-(S)-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 Streptomyces 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-i (1) exhibits significant inhibitory activity against HIV-1 protease with an IC50 value of 1.79 nM. A preliminary structure-activity relationship is discussed.