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

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.