Synthesis of the first example of a C2-C3/C2 '-C3 '-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer

We report the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1 -c][1,4]benzodiazepine (PBD) dimer 16 synthesised through a new and efficie nt route, thus establishing that C2-C3-endo unsaturation enhances both cyto toxicity and DNA-binding affinity in A-Ring-linked PBD dimers but to a less er extent than C2/C2'-exo-unsaturation. This new route has allowed the prep aration of multi-gram quantities of the related clinical candidate 1 and sh ould lead to more structurally diverse PBD dimer analogues. (C) 2001 Elsevi er Science Ltd. All rights reserved.