Journal article
Cocaine Benzoyl Thioester: Synthesis, Kinetics of Base Hydrolysis, and Application to the Assay of Cocaine Esterases
Chemical research in toxicology, Vol.11(8), pp.895-901
08/17/1998
Handle:
https://hdl.handle.net/2376/112812
PMID: 9705751
Abstract
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.
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Details
- Title
- Cocaine Benzoyl Thioester: Synthesis, Kinetics of Base Hydrolysis, and Application to the Assay of Cocaine Esterases
- Creators
- John R CashmanClifford E BerkmanGail UnderinerCarrie A KollyAllen D Hunter
- Publication Details
- Chemical research in toxicology, Vol.11(8), pp.895-901
- Academic Unit
- Chemistry, Department of
- Publisher
- American Chemical Society
- Identifiers
- 99900547939701842
- Language
- English
- Resource Type
- Journal article