Friedrich Schiller University Jena, Institute for Organic Chemistry and Macromolecular Chemistry, Humboldtstr. 10, 07743, Jena, Germany.
Friedrich Schiller University Jena Matthias Schleiden Institute of Genetics, Bioinformatics and Molecular Botany, Am Planetarium 1, 07743, Jena, Germany.
Chemistry. 2022 Apr 6;28(20):e202104417. doi: 10.1002/chem.202104417. Epub 2022 Mar 9.
A total synthesis of the cyclic lipodepsipeptide natural product orfamide A was achieved. By developing a synthesis format using an aminoacid ester building block and SPPS protocol adaptation, a focused library of target compounds was obtained, in high yield and purity. Spectral and LC-HRMS data of all library members with the isolated natural product identified the Leu residue to be d- and the 3'-OH group to be R-configured. The structural correction of orfamide A by chemical synthesis and analysis was confirmed by biological activity comparison in Chlamydomonas reinhardtii, which indicated compound configuration to be important for bioactivity. Acute toxicity was also found against Trypanosoma brucei, the parasite causing African sleeping sickness.
环脂肽天然产物orfamide A 的全合成已实现。通过开发使用氨基酸酯砌块和 SPPS 方案适应的合成格式，获得了高收率和高纯度的目标化合物的聚焦文库。所有文库成员的光谱和 LC-HRMS 数据以及分离的天然产物表明，Leu 残基为 d-构型，3'-OH 基团为 R-构型。orfamide A 的化学合成和分析结构校正通过在莱茵衣藻中的生物活性比较得到了证实，这表明化合物构型对生物活性很重要。该化合物对引起非洲昏睡病的寄生虫——布氏锥虫也具有急性毒性。
