An esterification method for synthesizing prodrugs of buprenorphine.
BACKGROUND
Buprenorphine is a potent analgesic. Extending its duration of action would make buprenorphine more valuable for clinical use. The depot formulation with prodrug design is a method used to prolong the duration of a short-acting drug. The aim of this study was to design and develop an esterification method to synthesize the prodrugs of buprenorphine and also to find out the detailed chemical characteristics of these prodrugs.


METHODS
A method of esterification was used. Buprenorphine prodrugs were synthesized by esterizing buprenorphine with various fatty acids and then purified by silica-gel column chromatography. The chemical structures of the prodrugs were affirmed by infrared, nuclear magnetic resonance and gas chromatography/mass spectrometries.


RESULTS
Six ester-type prodrugs of buprenorphine were successfully synthesized: buprenorphine propionate, pivalate, benzoate, valerate, enanthate, and decanoate.


CONCLUSIONS
A proper method for esterification of buprenorphine was developed. Six ester-type prodrugs of buprenorphine were successfully synthesized and the detailed chemical characteristics of these prodrugs were put forward.
Chin
Lin-Show
LS
Department of Orthopedic, Chi-Mei Medical Center, Tainan, Taiwan, ROC.
Huang
Kuo-Lun
KL
Liu
Kuo-Sheng
KS
Chu
Chin-Chen
CC
Tzeng
Jann-Inn
JI
Ho
Shung-Tai
ST
Wang
Jhi-Joung
JJ
D002047:Buprenorphine / Q000138:chemical synthesis*; D004951:Esterification; D011355:Prodrugs / Q000138:chemical synthesis*
D011355:Prodrugs; D002047:Buprenorphine