Synthesis of Sequence-Selective C8-Linked Pyrrolo[2,1-c][1,4]benzodiazepine DNA Interstrand Cross-Linking Agents
- 15 November 1996
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 61 (23) , 8141-8147
- https://doi.org/10.1021/jo951631s
Abstract
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.Keywords
This publication has 20 references indexed in Scilit:
- The relevance of drug DNA sequence specificity to anti-tumour activityEuropean Journal Of Cancer, 1994
- Structure of a Covalent DNA Minor Groove Adduct with a Pyrrolobenzodiazepine Dimer: Evidence for Sequence-Specific Interstrand CrosslinkingJournal of Medicinal Chemistry, 1994
- Comparison of a DSB-120 DNA Interstrand Cross-Linked Adduct with the Corresponding Bis-tomaymycin Adduct: An Example of a Successful Template-Directed Approach to Drug Design Based upon the Monoalkylating Compound TomaymycinJournal of Medicinal Chemistry, 1994
- Synthesis of 1-deoxycastanospermine and stereoisomersThe Journal of Organic Chemistry, 1992
- DNA as a target for drug actionTrends in Pharmacological Sciences, 1988
- Pyrrolo[1,4]benzodiazepine antitumor antibiotics: relationship of DNA alkylation and sequence specificity to the biological activity of natural and synthetic compoundsChemical Research in Toxicology, 1988
- A versatile and efficient synthesis of carbinolamine-containing pyrrolo[1,4]benzodiazepines via the cyclization of N-(2-aminobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetals: total synthesis of prothracarcinThe Journal of Organic Chemistry, 1987
- DNA sequence specificity of the pyrrolo[1,4]benzodiazepine antitumor antibiotics. Methidiumpropyl-EDTA-iron(II) footprinting analysis of DNA binding sites for anthramycin and related drugsBiochemistry, 1986
- A new method to synthesize .ALPHA.-aminoaldehydes.CHEMICAL & PHARMACEUTICAL BULLETIN, 1975
- 179. β-PseudognoscopineJournal of the Chemical Society, 1932