ABSTRACT
The generation of a natural-product-based library starting from andrographolide is described. Utilizing andrographolide itself in parallel solution-phase synthesis leads to a 360-membered library. The initial transformation of the starting material via ozonolysis is followed by the conversion into a suitable template by introduction of a thiazole moiety. Subsequent decoration at two points of diversity yields the desired natural product derivatives. The selection of actually synthesized compounds is based on a virtually generated library and the assessment of its members with respect to physicochemical parameters, thus ensuring pharmacological relevance of the compounds.
Subject(s)
Biological Products/chemical synthesis , Combinatorial Chemistry Techniques/methods , Diterpenes/chemistry , Indicators and Reagents , Models, MolecularABSTRACT
[structure: see text] The first enantioselective total synthesis of tonantzitlolone, a novel 15-membered macrocyclic diterpene, utilized a Julia olefination, a highly selective, potassium enolate-based anti-Felkin aldol reaction, and an E-selective ring-closing metathesis as key C-C bond-forming steps. The absolute configuration of tonantzitlolone is established.
Subject(s)
Diterpenes/chemical synthesis , Macrocyclic Compounds/chemical synthesis , Indicators and Reagents , Molecular Conformation , Stereoisomerism , ThermodynamicsABSTRACT
The phytochemical investigation of the leaves of Siparuna pauciflora yielded three novel sesquiterpenoids: the germacrane sipaucin A, the elemane sipaucin B and sipaucin C, comprising a new type of carbon skeleton. In addition, four known aporphine alkaloids-nor-boldine, boldine, laurotetanine, and N-methyl-laurotetanine-were obtained. The evaluation of the antiplasmodial activity of the isolated compounds against two strains of Plasmodium falciparum (PoW, Dd2) showed a moderate activity of nor-boldine.
Subject(s)
Monimiaceae/chemistry , Sesquiterpenes/isolation & purification , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/isolation & purification , Antiprotozoal Agents/pharmacology , Magnetic Resonance Spectroscopy , Plant Leaves/chemistry , Plasmodium falciparum/drug effects , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
Two new 3,4 dihydroxycinnamic acid esters have been isolated from Plazia daphnoides. The structures were elucidated by NMR spectroscopy.
Subject(s)
Asteraceae/chemistry , Caffeic Acids/chemistry , Caffeic Acids/isolation & purification , Esters , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Plant Components, Aerial/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purificationABSTRACT
In this study the in vitro antiplasmodial activities of extracts from Cussonia spicata (Araliaceae), Artemisia afra, Vernonia colorata, V. natalensis (Asteraceae), Parinari curatellifolia (Chrysobalanaceae), Clutia hirsuta, Flueggea virosa, (Euphorbiaceae), Adenia gummifera (Passifloraceae) and Hymenodictyon floribundum, (Rubiaceae) were evaluated. The lipophilic extracts from the aerial parts of Artemisia afra and Vernonia colorata proved to be the most active against the chloroquine-sensitive strain PoW and against the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Bioassay-guided fractionation of the extract of A. afra yielded seven flavonoids, from which acacetin, genkwanin and 7-methoxyacacetin showed in vitro activity; the IC(50) values ranged from 4.3 microgram/mL to 12.6 microgram/mL. In addition, several sesquiterpene lactones could be obtained from the most active fractions. Whereas eudesmaafraglaucolide proved to be inactive, the guaianolides 1-desoxy-1alpha-peroxy-rupicolin A-8-O-acetate, 1alpha,4alpha-dihydroxybishopsolicepolide and rupicolin A-8-O-acetate revealed in vitro antiplasmodial activity. Evaluation of V. colorata gained four sesquiterpenes 11beta,13-dihydrovernodalin, vernodalol, 11beta,13-dihydrovernolide and 11beta,13,17,18-tetrahydrovernolide, from which the first two constituents exhibited the strongest antiplasmodial activity (IC(50) values: 1.1-4.8 microgram/mL).
Subject(s)
Antiprotozoal Agents/pharmacology , Malaria, Falciparum/drug therapy , Phytotherapy , Plant Extracts/pharmacology , Plants, Medicinal , Plasmodium falciparum/drug effects , Animals , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/therapeutic use , Chloroquine , Drug Resistance , Humans , Inhibitory Concentration 50 , Medicine, African Traditional , Parasitic Sensitivity Tests , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Leaves , Plant Roots , Plant Stems , ZimbabweABSTRACT
The structure of the sesquiterpenes crispanone and crispane was revised to that of siol angelate and lasidiol angelate, respectively. A novel phenylpropanoid (apional) was also isolated.
ABSTRACT
A methanolic extract of Euphorbia terracina L. has been shown to contain two peracylated polyhydroxy terpenoid lactones with a novel C(22) carbon framework. These metabolites, which have been named terracinolides A (1) and B (2), are based on the same parent compound, but differ in the nature of one of the acyl residues. This novel skeletal system is formally derived from the jatrophane framework by addition of a two-carbon fragment on C-17 (jatrophane numbering).
