An efficient convergent synthesis of a homologous series of C8-linked pyrrolobenzodiazepine dimers with remarkable DNA interstrand cross-linking activity and potent in vitro cytotoxicity is reported. The 'amino thioacetal' cyclization procedure was used to produce the electrophilic DNA-interactive N10-C11 imine moiety during the final synthetic step. In order to construct the key A-ring fragments (9a-d), a versatile convergent approach has been developed to join two units of vanillic acid with α,ω-dihaloalkanes of varying length to provide the required bis(4-carboxy-2-methoxyphenoxy)alkanes while avoiding the formation of mixtures of monoalkylated and bisalkylated products.
ASJC Scopus subject areas
- Organic Chemistry