Current Organic Chemistry

ISSN: 1385-2728

Current Organic Chemistry
Volume 12, Number 8, May 2008

Contents

Natural Product Chemistry issue
Guest Editor: K. Hostettmann


Editorial Pp. 601


Inhibition of Leukotriene Biosynthesis by Secondary Plant Metabolites Pp. 602-618
Michael Adams and Rudolf Bauer
[Abstract]


Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance Pp. 619-628
Chunfeng Xie and Hongxiang Lou
[Abstract]


Chemistry, Distribution and Biological Activities of 13,28-Epoxy Oleanane Saponins from the Plant Families Myrsinaceae and Primulaceae Pp. 629-642
K. Foubert, M. Theunis, S. Apers, A.J. Vlietinck and L. Pieters
[Abstract]


Natural Products for Neglected Diseases: A Review Pp. 643-666
Jean-Robert Ioset
[Abstract]


General Articles


Study of Stability of New Mutual Prodrugs with Antimycobacterial Activity Pp. 667-674
Josef Jampilek, Zuzana Reckova, Ales Imramovsky, Ivan Raich, Jarmila Vinsova and Jiri Dohnal
[Abstract]


DTBS(di-tert-butylsilylene)-directed α-Galactosylation for the Synthesis of Biologically Relevant Glycans Pp. 675-689
Akihiro Imamura, Hiromune Ando, Hideharu Ishida and Makoto Kiso
[Abstract]




Abstracts

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Editorial

The 2007 Natural Product Chemistry issue of Current Organic Chemistry provides four chapters covering various bioactivities of natural products. The first contribution, by Adams and Bauer, involves plant metabolites which inhibit leukotriene biosynthesis. Leukotrienes, biosynthesized from fatty acids, play important roles in inflammation, bronchoconstriction, chemotaxis and blood vessel permeability. Inhibitors of leukotrienes are therefore of potential importance in several disease states. Although reviews of leukotriene biosynthesis inhibitors have been published, it is important to update advances made in the field and to discover new and more selective inhibitors. Plant metabolites provide an excellent source of such compounds. Bryophytes are also a source of novel metabolites. They have supplied many interesting isoprenoids and aromatic compounds. In China, there are over 3400 different species of bryophyte and Xie and Lou summarize data obtained in their laboratory on the constituents and bioactivities of a number of species, collected from all over China. Their focus is on the antifungal activities of the isolated compounds. This is because the explosion of opportunistic infections and the development of resistance to current antifungal drugs in humans urgently require new antifungal therapeuticals. Another area desperately in need of new therapeuticals is the domain of the so-called “neglected” diseases. Far too little funding and research goes into the tropical parasitic diseases leishmaniasis, sleeping sickness, Chagas disease and malaria. In the latter, though, there has been some improvement in the situation with the introduction of artemisinin. Artemisinin, a sesquiterpene lactone from the Chinese plant Artemisia annua (Asteraceae), is a very effective antimalarial compound which is important for the treatment of patients affected by resistant strains of the parasite. However, in order to be one step ahead of the resistance phenomenon, new drugs need to be in the pipeline. Ioset describes the most promising compounds for malaria and the other diseases that have recently been isolated from living organisms. A critical update is also provided on their current development status. The final contribution involves a sub-group of the saponins, the substance class which are glycosides of triterpenes or steroids. In this article, Foubert, Theunis, Apers, Vlietinck and Pieters treat the13,28-epoxy-oleanane saponins, almost all of which are found in species of the Primulaceae or Myrsinaceae plant families. They possess antiviral, haemolytic, molluscicidal and anti-angiogenic activities. In addition, there is a link to the article by Ioset because saponins from Maesa balansae (Myrsinaceae) have antileishmanial properties.

I would like to express my sincere thanks to all contributors in this volume for the excellent reviews of natural product research that they have produced.


Prof. K. Hostettmann
Université de Genève
Laboratoire de Pharmacognosie et Phytochimie
CH1211 Genève 4
Switzerland


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Inhibition of Leukotriene Biosynthesis by Secondary Plant Metabolites
Michael Adams and Rudolf Bauer

Leukotrienes (LTs) are a group of biologically highly potent mediators of inflammation, synthesised in the first metabolic step by 5-lipoxygenase from 20 carbon fatty acids, predominantly arachidonic acid. They include the cysteinyl leukotrienes LTC4, LTD4, LTE4, which cause bronchoconstriction, chemotaxis and enhanced blood vessel-permeability, and therefore play a major role in asthma, and the dihydroxyeicosatetraenoate LTB4, an important mediator for acute and chronic inflammatory ailments. Inhibition of leukotriene biosynthesis therefore is a promising target for combating a number of diseases. Plant secondary metabolites offer a structurally very diverse potential source of new therapeutic leads. The aim of this review is to update the current knowledge of plant compounds with inhibitory effects on leukotriene metabolism, by presenting results published in the last seven years. Substances are presented with their IC50 values together with the activities of the positive controls to enable better comparability. Inhibitory effects of extracts are not discussed.


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Chemical Constituents from the Chinese Bryophytes and Their Reversal of Fungal Resistance
Chunfeng Xie and Hongxiang Lou

The search for new antifungal agents was essential because of opportunistic infections in immunocompromised individuals and the development of resistance to currently used agents. Bryophytes offer a rich source of rare and structurally unique molecules and can serve as a reserve of potentially antifungal compounds for further development as pharmaceuticals. This minireview covered the chemical and biological research of Chinese bryophytes recently finished in our laboratory. Totally about 120 compounds have been isolated and identified from 17 bryophyte species collected from North to South of China. The antifungal effect of these isolated compounds and their reversal of resistance of Candida albicans to fluconazole were evaluated. The possible reversal mechanisms were also preliminarily tested.


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Chemistry, Distribution and Biological Activities of 13,28-Epoxy Oleanane Saponins from the Plant Families Myrsinaceae and Primulaceae
K. Foubert, M. Theunis, S. Apers, A.J. Vlietinck and L. Pieters

Saponins are a very diverse and large group of natural compounds, consisting of a glycan moiety linked to a triterpene or a steroid sapogenin. Part of these contain a 13,28-epoxy bridge, where C-28 can be a methylene, a hydroxymethylene or a carbonyl group. This review was restricted to those saponins possessing a completely saturated pentacyclic triterpene skeleton and a 13,28-epoxy bridge, in which C-28 was a methylene or a hydroxymethylene group, excluding the C-28 carbonyl derivatives (28→13 lactones). Almost all of these saponins have been found in members of the Primulaceae or Myrsinaceae plant families. The most important genera were Ardisia, Maesa, and Myrsine from the Myrsinaceae, and Cyclamen, Lysimachia, and Primula from the Primulaceae. Their structures were reviewed, biological activities discussed, and structure-activity relationships established.


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Natural Products for Neglected Diseases: A Review
Jean-Robert Ioset

Leishmaniasis, sleeping sickness (Human African Trypanosomiasis), Chagas’ disease (American Trypanosomiasis) and malaria are tropical parasitic diseases responsible for high mortality and morbidity each year in low-income countries. Due to the lack of vaccines and of safe, effective and affordable treatments, there is an urgent need to reinforce the existing therapeutic arsenal against these killers. One of the main opportunities is through the discovery of new molecules from natural origin. The gaps identified in the R&D process aiming to deliver new medicines for neglected diseases however also apply to natural products. A key review of the most promising antiprotozoal molecules recently discovered from natural resources is presented here together with a critical update on their current development status.


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Study of Stability of New Mutual Prodrugs with Antimycobacterial Activity
Josef Jampilek, Zuzana Reckova, Ales Imramovsky, Ivan Raich, Jarmila Vinsova and Jiri Dohnal

New mutual prodrugs of pyrazinamide, isoniazid, p-aminosalicylic acid and ciprofloxacine were designed and synthesised. All the prepared compounds were tested for their antimycobacterial activities. Several discussed compounds showed excellent biological effects against both Mycobacterium tuberculosis and some atypical strains. These activities were comparable with or higher than those of the standards (pyrazinamide, isoniazid, rifampicin). These interesting compounds are presented here, and their physico-chemical properties are discussed. Stabilities of all the studied compounds were measured by means of RP-HPLC method simulating conditions of biological testing. Decomposition half-times of individual mutual prodrugs were determined. Experimentally found data were processed using the program MATLAB, reaction orders and rate constants were calculated. The experimental results were subsequently correlated with ab initio/DFT calculations of electronic deficiency (δ⁺) in methine spacer connecting active parts of the molecule. The relationships between the chemical structure (π-electron density in the connecting CH linker) and the stability of the studied compounds are discussed.


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DTBS(di-tert-butylsilylene)-directed α-Galactosylation for the Synthesis of Biologically Relevant Glycans
Akihiro Imamura, Hiromune Ando, Hideharu Ishida and Makoto Kiso

This review outlines the chemistry of 1,2-cis glycosylations and discusses the state-of-the-art methods highlighting the DTBS-directed α-galactosylation recently developed by our group.