Sporothriolide电子圆二色谱的理论计算及其绝对构型的确定

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

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。

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：（ 3 a S,6 R,6 aR） and（ 3 aR,6 S,6 a S）. To confirm absolute configuration,time-dependent density functional theory [at MPW1 LYP/6-31 G（ d,p） level]is used to calculate the electronic circular dichroism（ ECD）. By comparing the calculated and the experimental spectra,（ 3 a S,6 R,6 aR）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.