合成BuprenorpMiie酯類前趨藥之方法

An Esterification Method for Synthesizing Prodrags of Buprenorphine

背景：Buprenorphine是一個強效的止痛劑，若能延長其療效將使buprenorphine對於臨床疼痛治療更具價值。將藥物製成前驅藥的形式再加入油中製成注射劑型是一種延長藥效作用的辦法。本研究的目的在建立一個合成buprenorphine酯類前趨藥之方法，而這些前驅藥的化學結構特性也將被鑑定。方法：本研究乃使用酯化法將buprenorphine與脂肪酸起酯化之反應，然後再以妙膠管柱來純化藥物。所合成之藥物結構我們再以紅內線儀，核磁共振儀，氣相層析/質譜儀來鑑定之。結果：六個buprenorphine酯類前趙藥被我們合成，它們是丙酸buprenorphine酯，三甲基乙酸buprenorphineI旨，苯甲酸buprenorphine醋，戌酸buprenorphine酯，庚酸buprenorphine酯及癸酸buprenorphine酯。結論：我們已找出並建立一個合成buprenorphine酯類前趨藥之方法與步驟，共有代表性的六個酯類前趨藥被合成。

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 bupre-norphine 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.