Synthesis of sequence-selective C8-linked pyrrolo[2,1-c][1,4]benzodiazepine DNA interstrand cross-linking agents

David E. Thurston, D. Subhas Bose, Andrew S. Thompson, Philip W. Howard, Alberto Leoni, Stephen J. Croker, Terrence C. Jenkins, Stephen Neidle, John A. Hartley, Laurence Hurley

Research output: Contribution to journalArticle

106 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)8141-8147
Number of pages7
JournalJournal of Organic Chemistry
Volume61
Issue number23
DOIs
StatePublished - Nov 15 1996
Externally publishedYes

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Vanillic Acid
Alkanes
Imines
DNA
Cyclization
Cytotoxicity
Dimers
pyrrolo(2,1-c)(1,4)benzodiazepine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis of sequence-selective C8-linked pyrrolo[2,1-c][1,4]benzodiazepine DNA interstrand cross-linking agents. / Thurston, David E.; Bose, D. Subhas; Thompson, Andrew S.; Howard, Philip W.; Leoni, Alberto; Croker, Stephen J.; Jenkins, Terrence C.; Neidle, Stephen; Hartley, John A.; Hurley, Laurence.

In: Journal of Organic Chemistry, Vol. 61, No. 23, 15.11.1996, p. 8141-8147.

Research output: Contribution to journalArticle

Thurston, DE, Bose, DS, Thompson, AS, Howard, PW, Leoni, A, Croker, SJ, Jenkins, TC, Neidle, S, Hartley, JA & Hurley, L 1996, 'Synthesis of sequence-selective C8-linked pyrrolo[2,1-c][1,4]benzodiazepine DNA interstrand cross-linking agents', Journal of Organic Chemistry, vol. 61, no. 23, pp. 8141-8147. https://doi.org/10.1021/jo951631s
Thurston, David E. ; Bose, D. Subhas ; Thompson, Andrew S. ; Howard, Philip W. ; Leoni, Alberto ; Croker, Stephen J. ; Jenkins, Terrence C. ; Neidle, Stephen ; Hartley, John A. ; Hurley, Laurence. / Synthesis of sequence-selective C8-linked pyrrolo[2,1-c][1,4]benzodiazepine DNA interstrand cross-linking agents. In: Journal of Organic Chemistry. 1996 ; Vol. 61, No. 23. pp. 8141-8147.
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AU - Bose, D. Subhas

AU - Thompson, Andrew S.

AU - Howard, Philip W.

AU - Leoni, Alberto

AU - Croker, Stephen J.

AU - Jenkins, Terrence C.

AU - Neidle, Stephen

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AU - Hurley, Laurence

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