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Pure Appl. Chem., 2011, Vol. 83, No. 9, pp. 1651-1674

Published online 2011-06-02

Synthesis of natural pyranonaphthoquinones and related antibiotic aza-analogues

Jan Jacobs1, Sven Claessens1, Kris Huygen2, Kourosch Abbaspour Tehrani3 and Norbert De Kimpe1*

1 Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium
2 Scientific Institute of Public Health Site Ukkel, Immunology and Vaccinology Program, Engelandstraat 642, B-1180 Brussels, Belgium
3 Organic Synthesis, Department of Chemistry, Faculty of Sciences, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium

Abstract: Pentalongin, the active principle isolated from the roots of the Central East African medicinal plant Pentas longiflora, revealing the basic skeleton of 3,4-dehydropyranonaphthoquinones, was synthesized by ring-closing metathesis of a suitable precursor. Mollugin, together with the (+)-cis-dihydroxylated analogue and the tetracyclic isagarin have been isolated from P. longiflora as well as from other rubiaceous herbs, which are often used in Chinese folk medicine. Synthetic routes of these natural products are presented, as well as the first syntheses of the natural products 3-hydroxy- and 3-methoxymollugin. Although pyranonaphthoquinones represent a large class of natural products, reports of their naturally occurring 2-aza analogues, all of which have been isolated as 2-aza-anthraquinones, are scarce in the literature. Nevertheless, this class of compounds has been found to possess interesting antitumor, antifungal, and antibiotic properties. Therefore, several synthetic routes to new classes of 2-aza-anthraquinones were developed. In vitro testing of the obtained compounds for their activity against Mycobacterium tuberculosis showed promising results.