An expedient synthesis of 7-O-functionalised pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones

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• 作者：Madani ; Hadi ; Thompson ; Andrew S. ; Threadgill ; Michael D.
• 关键词：pyrrolobenzodiazepine ; cyclisation ; carborane ; neutron capture therapy ; hydrogenoloysis
• 刊名：Tetrahedron
• 出版年：2002
• 出版时间：September 30, 2002
• 年：2002
• 卷：58
• 期：40
• 页码：8107-8111
• 全文大小：149 K

文摘

An efficient synthetic route to 7-hydroxypyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione, an important potential ligand for the DNA minor groove, has been developed. Simultaneous reduction of nitro and hydrogenolysis of the O-benzyl in N-(5-benzyloxy-2-nitrobenzoyl)-l-proline methyl ester, followed by thermal cyclisation, gave 7-hydroxypyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione. This was alkylated to give the prop-2-ynyl ether. Reaction of benzyl hex-5-ynoate with B₁₀H₁₄ and deprotection with HBr gave 4-(1,2-dicarbaclosododecaboran(12)-1-yl)butanoic acid. This acid was coupled with the tricyclic phenol to give 5,11-dioxo-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-7-yl 4-(1,2-dicarbaclosododecaboran(12)-1-yl)butanoate.