ABSTRACT
An investigation of the oxidative coupling products of some substituted hydroxynaphthazarins led to a revision of the proposed structure of islandoquinone, previously isolated from the lichen Cetraria islandica, and yielding (7aS*, 13aS*)-6,7a-diethyl-2,5,9,11,12,13a-hexahydroxy-7, 4-dioxabenzo[a]tetracene-1,4,8,13(7aH, 13aH)-tetraone through X-ray diffraction analysis of its 2,11-dimethyl ether.
Subject(s)
Lichens/chemistry , Naphthoquinones/chemistry , Models, Molecular , Molecular StructureABSTRACT
Six new highly oxygenated chromene derivatives, oxirapentyns F-K (2-7), one new polyketide (8), one new benzofurane (9), and two known cyclodepsipeptides, isoisariin B and isaridin E, were isolated from the lipophilic extract of the marine-derived fungus Isaria felina KMM 4639. The structures of compounds 2-9 were determined using spectroscopic methods. The relative configurations of compounds 2-7 were established through a combination of NOE data and spin coupling constants, and these results were confirmed by X-ray crystallographic analysis of 4. The absolute structures of all oxirapentyns were assumed based on their biogenetic relationship and confirmed using the modified Mosher's method on 2 and 7. Isariketide (8) showed moderate cytotoxicity toward HL-60 cells.
Subject(s)
Alkynes/isolation & purification , Antineoplastic Agents/isolation & purification , Benzopyrans/isolation & purification , Depsipeptides/isolation & purification , Geologic Sediments/chemistry , Hypocreales/chemistry , Alkynes/chemistry , Alkynes/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Benzopyrans/chemistry , Benzopyrans/pharmacology , Cell Survival/drug effects , Crystallography, X-Ray , Depsipeptides/chemistry , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Marine Biology , Microbial Sensitivity Tests , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Oceans and SeasABSTRACT
The concise synthesis of the lichen-derived antitumor agent hybocarpone (1) and its analogs is described. A new synthetic approach is based on the direct oxidative dimerization of the available naphthazarin precursors in the formation of the binaphtho[2,3-b; 2,3-d]furantetraone structure. It was shown that the first step to tetrahydrofuran features is the bridging hindered S*,S* and R*,S* carbon-carbon bonds of the molecules, setting the relative configurations of the 5aS*,6aS*,12aS*,12bS* and 5aS*,6aR*,12aR*,12bS* diastereomers.
