Sporothriolide电子圆二色谱的理论计算及其绝对构型的确定

Sporothriolide(6-己基-3-亚甲基四氢呋喃3,4-b]呋喃-2,4-酮)最早是从Sporothrix sp.(孢子丝菌)中发现的一种抗真菌化合物。经核磁共振谱图解析,发现它是一个聚酮化合物;其化学结构中含有3个手性碳中心;并具有两种相对构型,即(3a S,6R,6aR)和(3aR,6S,6a S)。为了确定绝对构型,采用含时密度泛函方法,在MPW1LYP/6-31G(d,p)水平上计算了电子圆二色谱。通过与实测谱图的比对,其绝对构型被确定为(3a S,6R,6aR)。五元环的左手构象和右手构象产生了镜像对称的电子圆二色谱,表明五元环的构象翻转对其圆二色谱具有重要影响。此外,溶剂甲醇与sporothriolide之间的分子间氢键导致了低于14.1 nm的Cotton效应偏移,及低于75 cgs的峰强度的增强,说明溶剂化效应对sporothriolide的圆二色谱影响不大。

Theoretical Calculation of Electronic Circular Dichroism of Sporothriolide and Determination of Absolute Configuration

Sporothriolide (6-hexyl-3-methylene tetrahydrofuran 3, 4-b] furan-2,4-dione), firstly discovered from Sporothrix sp. (filamentous bacteria), is a kind of antifungal compound. It is a poly ketone compound, which is demonstrated by nuclear magnetic resonance (NMR) spectra. The chemical structure contains three chiral carbon centers and two possible relative configurations: (3aS,6R,6aR) and (3aR,6S,6aS). To confirm absolute configuration, time-dependent density functional theory (at MPW1LYP/6-31G(d,p) level) is used to calculate the electronic circular dichroism (ECD). By comparing the calculated and the experimental spectra, (3aS,6R,6aR) is identified. The right- and left-handed conformations of five membered rings lead to mirror symmetrical CDs, indicating the important influence of ring-flip of five membered ring on the CD. In addition, the intermolecular hydrogen bond between sporothriolide and solvent methanol leads to Cotton Effect shift less than 14.1 nm and enhancement of the peak intensity less than 75 cgs. It suggests that the solvation effect has little influence on the CD of sporothriolide.