PhD Scientific Days 2024

Budapest, 9-10 July 2024

Pharmaceutical Sciences and Health Technologies II.

Synthesis and characterisation of novel morphinan esters


Balázs Simon1
1: Semmelweis Egyetem GyTK Gyógyszerészi Kémiai Intézet

Text of the abstract

Morphine and its derivatives are still widely used in medicine for various purposes. Their main use can be found in their effective pain relief, but side effects limit often limit this. Synthetising new, more potent derivatives could help, because with lower doses, the more serious side effects could be avoided more easily, which would help the management of serious pain in patients. A possible structural modification is esterification of the hydroxyl groups found in morphine derivatives in the 6th and 14th positions, and this could lead to derivatives with the desired properties.
We aim to synthetise and characterise 6-OH-esters of morphine derivatives with the use of five selected acyl chlorides. After the sythesis, we aim to characterise the compounds with the use of NMR spectroscopy and mass spectometry.
The five selected acids (palmitic acid, stearic acid, diphenylacetic acid, cinnamic acid, and dihydrocinnamic acid) were turned into their respective acyl chlorides with thionyl chloride. They were reacted with 3-O-acetyl-morphine, 3-O-acetyl-dihydromorphine, codeine, and dihydrocodeine to form their respective esters, in dichloromethane. The reactions were cathalysed with 4-dimethylaminopyridine. The esters were purified with recrystallisation from the appropriate solvent, or with column chromatography when needed. Their characterisation is done on a 400 MhZ NMR instrument, and with MS methods.
The esterification reactions proceeded in good yield, and their spectral data proved their purity.
Our work provided us with novel derivatives of morphine, which we were able to characterise. Hopefully, these compounds will prove as useful tools in pain management.

e-mail adress:
Semmelweis University
Dr. Sándor Hosztafi