Cashman J R, Berkman C E, Underiner G, Kolly C A, Hunter A D
Human BioMolecular Research Institute, 1604 29th Avenue West, Seattle, Washington 98199, USA.
Chem Res Toxicol. 1998 Aug;11(8):895-901. doi: 10.1021/tx9800203.
The synthesis and characterization of diastereomers of cocaine benzoyl thioester is described. Allococaine benzoyl thioester and allopseudococaine benzoyl thioester were synthesized by the conjugate addition of p-methoxytolyl thiol to ecgonine methyl ester followed by debenzylation and benzoylation. The absolute structure of the hydrochloride salt of the major ecgonine p-methoxytolyl sulfide formed was determined by single-crystal diffraction analysis and used to establish the addition geometry. When placed in aqueous solution, the cocaine benzoyl thioester diastereomers hydrolyzed to give thioecgonine methyl ester. The rate of cocaine benzoyl thioester hydrolysis was carefully investigated spectrophotometrically by using the Ellman reagent. At neutral pH, the hydrolysis of the diastereomers was found to proceed at detectable rates. Upon increasing pH, the rate of hydrolysis of cocaine benzoyl thioester diastereomers was increased and the reaction was catalyzed by basic buffer species. In addition to defining the kinetics of hydrolysis in aqueous solution, cocaine benzoyl thioester was utilized as a highly efficient method to monitor the activity of cholinesterases and pig liver esterase. Use of cocaine benzoyl thioester represents a rapid and sensitive way to screen for cocaine esterase activity.
描述了可卡因苯甲酰硫酯非对映异构体的合成与表征。通过对芽子碱甲酯进行对甲氧基甲苯硫醇的共轭加成，然后进行脱苄基化和苯甲酰化反应，合成了别可卡因苯甲酰硫酯和别假可卡因苯甲酰硫酯。通过单晶衍射分析确定了所形成的主要芽子碱对甲氧基甲苯硫醚盐酸盐的绝对结构，并用于确定加成几何结构。当置于水溶液中时，可卡因苯甲酰硫酯非对映异构体会水解生成硫代芽子碱甲酯。使用埃尔曼试剂通过分光光度法仔细研究了可卡因苯甲酰硫酯的水解速率。在中性pH值下，发现非对映异构体的水解以可检测的速率进行。随着pH值升高，可卡因苯甲酰硫酯非对映异构体的水解速率增加，并且该反应由碱性缓冲物质催化。除了确定在水溶液中的水解动力学外，可卡因苯甲酰硫酯还被用作监测胆碱酯酶和猪肝酯酶活性的高效方法。使用可卡因苯甲酰硫酯是一种快速且灵敏的筛选可卡因酯酶活性的方法。
