Synthesis of Benzimidazolequinone Analogue of Cyclopropamitosene Antitumor Agents

John O’Shaughnessy; Desmond Cunningham; Paul Kavanagh; Dónal Leech; Patrick McArdle; Fawaz Aldabbagh

doi:10.1055/s-2004-831341

LETTER

Synthesis of Benzimidazolequinone Analogue of Cyclopropamitosene Antitumor Agents

John O’Shaughnessy, Desmond Cunningham, Paul Kavanagh, Dónal Leech, Patrick McArdle, Fawaz Aldabbagh*
Department of Chemistry, National University of Ireland, Galway, Ireland
Fax: +353(91)525700; e-Mail: Fawaz.Aldabbagh@nuigalway.ie;

Abstract

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Abstract

The preparation of a pyrrolo[1,2-a]benzimidazole, pyrido[1,2-a]benzimidazole and pyrrolo[1,2-a]benzimidazolequinone containing a fused cyclopropane ring is reported. Their synthesis involved the thermolysis of the respective benzimidazole-2-Eschenmoser hydrazones (aziridinyl imines), which facilitated an intramolecular 1,3-dipolar cycloaddition. X-ray crystal structure of one [3+2] pyrazoline-cycloadduct is presented. The redox potential of -1.052 V (vs. ferrocene) for the cyclopropapyrrolo[1,2-a]benzimidazolequinone was determined by cyclic voltammetry indicating single-electron reduction occurs more easily than mitomycin C or the cyclopropamitosenes.

Key words

benzimidazoles - bioreductive - diazo-compounds - heterocycles - hydrazones

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References

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1,1a,8,8a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-a]benz-imidazole-3,6-dione (3): red-orange solid, mp 119-120 °C. IR (neat): 1653 (C=O), 1507, 1292, 1072, 1053 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.77-0.80 (m, 1 H, 1-H), 1.43-1.49 (m, 1 H, 1-H), 2.52-2.56 (m, 2 H, 1a-H and 8a-H), 4.28-4.30 (m, 2 H, 8-CH₂), 6.54-6.65 (AB-q, J = 10.3 Hz, 2 H, 4-H and 5-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2
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