ω-氯甲基长叶烯的合成及抑菌活性

Synthesis, Antibacterial Activity, and Antifungal Activity of ω-Chloromethyl Longifolene

摘要:

以ω-羟甲基长叶烯（Ib）为原料，经过卤代反应，合成了ω-氯甲基长叶烯（Ic），产物经FTIR，1HNMR， 13CNMR和 HRMS（ESI）等进行了结构表征。考察了反应温度、反应物配比〔n(SOCl2):n(Ib)〕和反应时间对卤代反应的影响。结果表明：在较佳的反应条件（反应温度85℃，n(SOCl2)/n(Ib)=1.10，反应时间6h）下，Ic的产率达94.2%。初步的抑菌活性实验结果表明：Ic对金黄色葡萄球菌、肺炎克雷伯氏菌和白色念珠菌的生长具有明显的抑制作用，其最低抑菌浓度分别为31.3、62.5和125mg/L，且远小于长叶烯的最低抑菌浓度（>500mg/L）。运用密度泛函理论（DFT），采用B3LYP/6-31G方法对Ic和长叶烯进行几何结构优化，结果表明，Ic抑菌活性高于长叶烯与Ic的前线轨道能隙（0.063 a.u）较长叶烯（0.256 a.u）小有关。

Abstract:

ω-Chloromethyl longifolene (Ic) was synthesized via halogenation of ω-hydroxymethyl longifolene (Ib) with thionyl chloride as halogenating reagent and structurally characterized by means of FTIR, 1HNMR，13CNMR and HRMS (ESI). There were obvious effects of reaction temperature, reaction time and material ratio on the halogenations reaction. Under the optimum reaction conditions (85°C, 6h, molar ratio for thionyl chloride: compound Ib=1.10:1.00), the yield of compound Ic was up to 94.2%. The preliminary biological activity test showed that Ic could obviously inhibit the growth of two bacteria (staphylococcus aureus and Canidia Albicans) and one fungus (Klebsiella pneumonia) with MIC 31.25, 62.5, and 125mg/L, respectively, comparing with 500mg/L of MIC of longifolene. It was found that Ic exhibited obviously higher antimicrobial activity, which was associated with its lower HOMO (highest occupied molecular orbital)/LUMO (lowest unoccupied molecular orbital) energy gap (0.063 a.u), comparing with that of longifolene (0.256 a.u) calculated using the density function theory (DFT) at B3LYP/6-31G level.