6533b7dcfe1ef96bd1272799

RESEARCH PRODUCT

The first sorbicillinoid alkaloids, the antileukemic sorbicillactones A and B, from a sponge-derived Penicillium chrysogenum strain

Katja MaksimenkaStefan SteffensSanja Perović-ottstadtHideyuki TsurutaJörg MühlbacherRüdiger StöhrJutta WieseGerhard LangOlexandra BoreikoGerhard BringmannTobias A. M. GulderJohannes F. ImhoffKarsten SchaumannWerner E.g. Müller

subject

AlanineCircular dichroismMethionineStrain (chemistry)biology010405 organic chemistryStereochemistryOrganic Chemistry010402 general chemistryMass spectrometryPenicillium chrysogenumbiology.organism_classification01 natural sciencesBiochemistry3. Good health0104 chemical scienceschemistry.chemical_compoundSpongechemistryBiochemistryDrug DiscoveryTwo-dimensional nuclear magnetic resonance spectroscopy

description

The saltwater culture of a Penicillium chrysogenum strain isolated from the Mediterranean sponge Ircinia fasciculata yielded three new sorbicillin-derived compounds (1-3), whose structures were elucidated mainly by 2D NMR and mass spectrometry. Among them, sorbicillactones A (1) and B (2) are the first sorbicillinoid natural products that contain nitrogen. Compound 1 is anti-HIV active and it exhibits a strong cytotoxic activity against L5178y leukemic cells, combined with a relatively low toxicity to cervical carcinoma HeLa S3 cells and pheochromocytoma PC 12 cells. The absolute configurations of I and 2 were elucidated by quantum chemical calculation of circular dichroism (CD) spectra. Another compound isolated, sorbivinetone (3), might be an artifact derived from sorbicillinol (4) by Diels-Alder reaction with ethyl vinyl ether. Furthermore, the known sorbicillinoid fungal metabolites oxosorbicillinol (5), sorbicillin (6), and bisvertinolone (7) were identified, as well as the alkaloids meleagrine and roquefortine C. The biosynthetic origin of sorbicillactone A (1) from acetate, alanine, and methionine was investigated by feeding experiments with C-13-labeled precursors

yearjournalcountryeditionlanguage
2005-07-01Tetrahedron
https://doi.org/10.1016/j.tet.2005.05.026