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. 2011 Jan-Mar;79(1):59-68.
doi: 10.3797/scipharm.1011-11. Epub 2010 Dec 18.

The gramine route to pyrido[4,3-b]indol-3-ones - identification of a new cytotoxic lead

Uwe Wollein  1 , Franz Bracher
Affiliations

The gramine route to pyrido[4,3-b]indol-3-ones - identification of a new cytotoxic lead

Uwe Wollein et al. Sci Pharm. 2011 Jan-Mar.

Abstract

A novel approach to 3-oxo-γ-carbolines was worked out starting from methyl indol-2-ylacetate via a gramine derivative. After quaternization, ammonia and 4-methoxybenzylamine could be inserted giving appropriate 3-oxo-γ-carbolines. Condensation with 2-chlorobenzaldehyde under microwave irradiation gave a 4-(2-chlorobenzyl)-3-oxo-γ-carboline. N-methylation lead to a product with very promising antifungal and cytotoxic activities.

Keywords: Antifungal activity; Cytotoxic activity; Gramine; Lactam; gamma-Carboline.

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Figures

Fig. 1.
Fig. 1.
Bauerine C (A), 3-oxo-γ-carboline (B), latrepirdine (C), mebhydrolin (D), alosetron (E), arylidene oxindoles (F)
Sch. 1.
Sch. 1.
a) N,N-dimethylmethyleneiminium chloride, dichloromethane, r.t., 1 h (61%); b) iodomethane, tetrahydrofuran, r.t., 1 h; c) conc. ammonia, r.t., 12 h (51% over 2 steps); d) 4-methoxy-benzylamine (neat), r.t., 12 h (34% over 2 steps).
Sch. 2.
Sch. 2.
e) 2-chlorobenzaldehyde, potassium fluoride/aluminium oxide, microwave irradiation (20%); f) iodomethane, potassium tert-butoxide, dimethyl sulfoxide, 80 °C, 2 h (24%).
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References

    1. Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007;70:461–477. doi: 10.1021/np068054v. - DOI - PubMed
    1. Cao R, Peng W, Wang Z, Xu A. ß-Carboline alkaloids: Biochemical and pharmacological functions. Curr Med Chem. 2007;14:479–500. doi: 10.2174/092986707779940998. - DOI - PubMed
    1. Bracher F, Hildebrand D. ß-Carbolin-Alkaloide, I: Synthese von 1-Aryl- und 1-Alkenyl-ß-carbolinen durch Palladium-katalysierte Kupplungsreaktionen. Liebigs Ann Chem. 1992:1315–1319. doi: 10.1002/jlac.1992199201216. - DOI
    1. Bracher F, Hildebrand D. ß-Carbolin-Alkaloide, 3. Mitt.: Synthese von Harmalacidin und Strychnocarpin. Pharmazie. 1993;48:695.
    1. Pohl B, Luchterhandt T, Bracher F. Total syntheses of the chlorinated β-carboline alkaloids bauerine A, B, and C. Synth Commun. 2007;37:1273–1280. doi: 10.1080/00397910701226228. - DOI

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