Title
Synthesis of 3-O-Carboxyalkyl Morphine Derivatives and Characterization of Their Acid-Base Properties
Author
Istvan Koteles, Karoly Mazak, Gergo Toth, Peter Horvath, Eszter Kiss, Boglarka Tuz, Sandor Hosztafi
Year
2021
Journal
CHEMISTRY & BIODIVERSITY
Abstract
The C-3 phenolic hydroxy group containing morphine derivatives (morphine, oxymorphone, naloxone, naltrexone) are excellent candidates for the synthesis of 3-O-functionalized molecules. Achieving free carboxylic group containing derivatives gives the opportunity for further modification and conjugation that could be used for immunization and immunoassays. For this purpose ethyl bromo- and chloroacetate can be used as O-alkylating agents. Hydrolyzing the products affords the appropriate free carboxylic group containing 3-O-carboxyalkyl derivatives. As these molecules contain an acidic and a basic functional group the protonation macro- and microconstants were determined too, using pH-potentiometry and NMR-pH titration, beside fully characterizing their structure using IR, CD, NMR and HR-MS measurements.
Instrument
J-720
Keywords
C-3, phonolic hydroxy group, morphine derivatives