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(−)‐(S)‐Flunoxaprofen and (−)‐(S)‐naproxen isocyanate: Two new fluorescent chiral derivatizing agents for an enantiospecific determination of primary and secondary amines
Author(s) -
Martin E.,
Quinke K.,
Spahn H.,
Mutschler E.
Publication year - 1989
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530010308
Subject(s) - chemistry , enantiomer , reagent , naproxen , isocyanate , derivatization , chiral derivatizing agent , chromatography , organic chemistry , combinatorial chemistry , chloroformate , high performance liquid chromatography , chiral column chromatography , medicine , alternative medicine , pathology , polyurethane
The synthesis and analytical testing of two new fluorescent chiral derivatizing agents (−)‐(S)‐flunoxaprofen and (−)‐(S)‐naproxen isocyanate, is described. In a few simple steps the free carboxylic acids [(S)‐flunoxaprofen and (S)‐naproxen] are activated with ethyl chloroformate/sodium azide and transformed to the corresponding isocyanates. The crystalline reaction products display high enantiomeric and chemical purity and stability. The direction of the optical rotation of both substances is inverse to that of the corresponding carboxylic acids. At ambient temperature the reagents swiftly react with primary and secondary amines, yielding highly fluorescent ureas. The applicability of the two reagents for the resolution of racemic amines was tested with a number of pharmaceuticals (antiarrhythmics, β‐adrenergic antagonists, calcium channel blockers, centrally acting antidepressants). The diastereoisomeric derivatives were efficiently resolved and separated from side‐products by means of normal and reversed‐phase high‐performance liquid chromatography (HPLC). The use and sufficient sensitivity of the two reagents for pharmacokinetic studies were demonstrated with a determination of plasma levels of propranolol enantiomers after oral administration of the racemic drug [80 mg (R,S)‐propranolol‐HCl] to two volunteers.