Pyrrolo indole quinones

FIGURE 7.18 pH-rate profile for the disappearance pyrrolo[l,2-a]indole quinone methide. 

TABLE 7.1 Results of Screening of the Pyrido[l,2-a]indole and the Pyrrolo[l,2-a] indole Quinones (Structures Shown in Scheme 7.18)... 

To assess the trapping of biological nucleophiles, the pyrido[l,2-a]indole cyclopropyl quinone methide was generated in the presence of 5 -dGMP. The reaction afforded a mixture of phosphate adducts that could not be separated by reverse-phase chromatography (Fig. 7.16). The 13C-NMR spectrum of the purified mixture shown in Fig. 7.16 reveals that the pyrido [1,2-a] indole was the major product with trace amounts of azepino[l,2-a] indole present. Since the stereoelec-tronic effect favors either product, steric effects must dictate nucleophilic attack at the least hindered cyclopropane carbon to afford the pyrido[l,2-a]indole product. Both adducts were stable with elimination and aromatization not observed. In fact, the pyrido [1,2-a] indole precursor (structure shown in Scheme 7.14) to the pyrido [l,2-a]indole cyclopropyl quinone methide possesses cytotoxic and cytostatic properties not observed with the pyrrolo [1,2-a] indole precursor.47... 

SCHEME 7.18 Formation and fate of the pyrrolo[l,2-a]indole (w — 0) and the pyrido[l,2-a] indole-based ( = 1) quinone methides. 

The rate constants associated with the acid-catalyzed conversion of the pyrido[ 1,2- ]indole hydroquinone to its quinone methide were too large to measure. We did manage to measure two rate constants at pH 7 and 8, both with a value of 0.36 min-1. Based on the pH-rate profile obtained the pyrrolo 1,2-a indole hydroquinone, these... 

KhdourO. SkiboE. B. Chemistry of pyrrolo[l,2-a]indole- andpyrido[l,2-a]indole-based quinone methides. Mechanistic explanations for differences in cytostatic/cytotoxic properties. J. Org. Chem. 2007, 72, 8636-8647. 

As part of an examination of an oxidative coupling of methyl 6-hydroxyindole-2-carboxylate with primary amines which enabled the development of a facile preparation of 2-substituted methyl pyrrolo[2,3-e]benzoxazole-5-carboxylates, the reaction of this indole with 1,2-diaminoethane and excess Mn02 gave compound (83) in an apparent intramolecular interception of a transient intermediate o-quinone monoimine (Equation (46)) <88JOC5163>. 

General name for antitumor antibiotics with benzo-quinone and aziridine structural units from cultures of streptomycetes (e. g., Streptomyces lavendulae, S. ver-ticillatus, S. caespitosus). There are more than 15 natural variants containing a pyrrolo) 1,2-a)indole system and differing in R and R, with OH in place of OCHj at C-9a, and different stereochemistries at C-9. The violet to blue-violet, optically active M. crystallize readily and are soluble in water, methanol, and acetone. A cluster of 47 bacterial genes that control biosynthesis of M. C has been characterised. The biosynthetic building block of the benzoquinone (C7N) unit is 3-amino-5-hydroxybenzoic acid, several total syntheses have been repotted. 

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