Economical Synthesis of 13C-Labeled Opiates Cocaine Derivatives and Selected Urinary Metabolites by Derivatization of the Natural Products

摘要

The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, ¹³C-labeled compounds are useful for identification and quantification purposes by mass spectroscopic techniques, potentially increasing accuracy by minimizing ion alteration/suppression effects. Thus, the synthesis of [acetyl-¹³C4]heroin, [acetyl-¹³C4-methyl-¹³C]heroin, [acetyl-¹³C2-methyl-¹³C]6-acetylmorphine, [N-methyl-¹³C-O-metyl-¹³C]codeine and phenyl-¹³C6-labeled derivatives of cocaine, benzoylecgonine, norcocaine and cocaethylene was undertaken to provide such reference materials. The synthetic work has focused on identifying ¹³C atom-efficient routes towards these derivatives. Therefore, the ¹³C-labeled opiates and cocaine derivatives were made from the corresponding natural products.