手性苄基甲基亚砜的氯过氧化物酶催化定向合成

Asymmetry Synthesis of Chiral Sulfoxide Catalyzed by Chloroperoxidase

基于氯过氧化物酶(CPO)对有机底物的手性识别功能,以CPO催化、叔丁基过氧化氢(TBHP)氧化甲基苄基硫醚合成手性R-苄基甲基亚砜,并在反应体系中引入多羟基化合物及季铵盐提高了目标产物的产率;反应主要受体系的pH值、氧化剂类型、反应时间、氧化剂/底物摩尔比,以及CPO用量等因素控制.引入多羟基化合物(甘油,PEG400,PEG600)时,R-苄基甲基亚砜的产率及ee值可分别达到65.5%和96.3%;而引入季铵盐(TEABr,TPABr,TBABr)时,其产率提高到78.2%～68.5%,ee值为95.4%～94%.UV-vis及荧光光谱分析表明反应体系中引入少量添加剂时CPO活性中心的血红素辅基暴露程度增加,底物容易接近,同时CPO的α-螺旋结构得以加强,从而有效改善了CPO的催化性能.与目前的合成方法相比,CPO酶促氧化制备手性R-苄基甲基亚砜高效、定向,酶用量极少,具有一定的产业化应用潜能.

Benzyl alkyl sulfide was turned into chiral R-sulfoxide using chloroperoxidase（CPO）-catalyzed oxidation of（TBHP） based on CPO＇s chiral recognization to organic substrate.The yield of aim products was enhanced by the introduction of polyhydroxy compound and quaternary ammonium salt.The reaction was mainly controlled by factors such as pH,oxidants,reaction time,molar ratio of oxidant/substrate,and CPO consumption.The sulfoxide yield and enantiomeric excess（ee） reached 65.5% and 96.3% when poly-hydroxy compounds（glycerol,PEG400 or PEG600） were introduced into reaction system.The yield and ee of 78.2%～68.5% and 95.4%～94% were obtained when quaternary ammonium salt（TEABr,TPABr or TBABr） was introduced.UV-vis and fluorescence spectrum assay indicated that it was easier for CPO to bind with the substrate because the introduction of above additives would intensify the exposure of heme.Moreover,it was also favorable for CPO catalytic performance due to the improvement of α-helix structure of CPO.Compared to those reported methods,the preparation of chiral sulfoxide catalyzed by CPO was very efficient.CPO consumption was very small which would ensure its potential application in industry.