Isolation and computer-based structural determination of madangolide b

Madangolide (1) is a 17-membered cyclic enamide isolated from the marine cyanobacterium Lyngbya bouillonii. Since its discovery in 1999, the relative and absolute configurations of 1 have remained unknown. Here, we report the isolation, structural determination, and biological activity of a new analog of madangolide (1), madangolide B (2), from a marine Moorena sp. cyanobacterium. The planar structure of 2 was established using conventional two-dimensional NMR spectroscopy. The absolute configuration was clarified by comparing the experimental and theoretical data, including the chemical shifts, homonuclear and heteronuclear coupling constants, and ECD spectra. Based on the similarity of the NMR data, we proposed an absolute configuration of madangolide (1) and verified it through degradation and derivatization reactions. This study demonstrates the effectiveness of modern computational chemistry in revealing the stereochemistry of complex natural products with conformational flexibility.

Methods
All NMR spectral data were recorded on a JEOL JNM-ECX-400 or a JNM-ECS-400 spectrometer.

马达诺利德（madangolide）(1)是一种17元环烯酰胺，最初从海洋蓝藻Lyngbya bouillonii中分离得到。自1999年被发现以来，其相对构型与绝对构型始终未被阐明。本研究从海洋Moorea属蓝藻中分离得到了马达诺利德（madangolide）的新型类似物马达诺利德B（madangolide B）(2)，并报道了其分离方法、结构解析结果与生物活性。通过常规二维核磁共振（NMR）波谱学手段确定了化合物2的平面结构。借助对比实验数据与理论计算数据（包括化学位移、同核及异核耦合常数以及电子圆二色性（ECD）光谱），明确了化合物2的绝对构型。基于核磁共振数据的相似性，我们推定了马达诺利德（madangolide）(1)的绝对构型，并通过降解反应与衍生化反应对该推定进行了验证。本研究证实了现代计算化学在解析具有构象灵活性的复杂天然产物立体化学方面的有效性。

实验方法
所有核磁共振波谱数据均在JEOL JNM-ECX-400或JNM-ECS-400型核磁共振波谱仪上采集。