155203-01-3

Usage

Uses

Used in Pharmaceutical Industry:
(αS,5α,7α)-4,5-Epoxy-7-(1-hydroxy-1,2,2-trimethylpropyl)-3,6-dimethoxy-6,14-ethenomorphinan-17-carbonitrile is used as an intermediate in the synthesis of 18,19-Dehydrobuprenorphine (D229310), an analogue of Buprenorphine (B689570). Buprenorphine is a potent opioid analgesic used to treat moderate to severe pain and is also utilized in medication-assisted treatment for opioid addiction. The compound's role in the synthesis process is essential for producing a more effective and potentially safer alternative to existing treatments.

Upstream product

• 506-68-3 bromocyane 
• 13965-70-3 4,5α-epoxy-6α,14α-etheno-7α-(1-hydroxy-1,2,2-trimethylpropyl)-3,6β-dimethoxy-17-methylmorphinan 
• 115-37-7 thebaine 
• 15358-22-2 thevinone 

Downstream Products

• 52485-79-7 Buprenorphine 

Relevant academic research and scientific papers

Synthesis and pharmacological evaluation of 18,19-Dehydrobuprenorphine

18,19-Dehydrobuprenorphine (2) was prepared in five steps starting from thevinone (3) which is readily available from thebaine by Diels-Alder reaction. Grignard reaction with tert-BuMgBr afforded tert-butylthevinol (4) which was N-demethylated via N-cyano-tert-butylthevinol (5) using BrCN. Alkali treatment gave N-nor-tert-butylthevinol (6) which was alkylated with cyclopropylmethyl bromide to give N-cyclopropylmethyl-tert-butylthevinol (7), followed by ether cleavage with thiolate to yield 2. 18,19-Dehydrobuprenorphine displayed in opioid receptor binding studies very high affinity for μ receptors, while the affinity for κ and δ receptors was lower. In the tail-flick test in mice, compound (2) was 25 times more potent than morphine and ca. 2.5 times as potent as buprenorphine.

PROCESS FOR THE SYNTHESIS OF BUPRENORPHINE

The present invention relates to a novel route of synthesis for the opioid receptor antagonist Buprenorphine or a pharmaceutically acceptable salt thereof, starting from thebaine, wherein the route comprises the reaction of the baine with a dienophile; forming an alkylated reaction product by reaction with a Grignard-reagent; formation of an cyanamide; deprotection of the cyanamide- and the phenolic-oxygen-moiety, wherein the cleavage of one or both groups is performed in the presence of an alkali or alkaline earth sulfide; followed by derivatization with a cyclopropyl-halogen and hydrogenation to yield Buprenorphine.