The absolute configuration of peroxisomicines A1 and A2

• Published in: Tetrahedron Vol. 60; no. 38; pp. 8547 - 8552
• Main Authors: Pérez, Alejandro, Ramírez-Durón, Rosalba, Piñeyro-López, Alfredo, Waksman, Noemí, Reichert, Matthias, Bringmann, Gerhard
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 13.09.2004; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Chiral displacement reagent; Circular dichroism; Degradation; Dihydroxyanthracenones; Peroxisomicine; Physical Sciences; Science & Technology; Degradation; Chiral displacement reagent; Dihydroxyanthracenones; Peroxisomicine; Circular dichroism; A; degradation; chiral displacement reagent; circular dichroism; dihydroxyanthracenones; peroxisomicine
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2004.06.123

Peroxisomicine A1 is a potentially antineoplastic compound isolated from the seeds of Karwinskia parvifolia. It is considered as a useful chemotype for the preparation of topoisomerase II targeted anticancer cells. Stereochemically, it is characterized by the presence of two stereocenters and a rotationally hindered and thus likewise stereogenic biaryl axis. In this contribution, the absolute configuration of peroxisomicine A1 and its epimer, peroxisomicine A2, was established by means of a five-step degradative procedure giving the respective R- and S-configured methyl 2-(2′-methyl-5′-oxotetrahydrofuryl)acetates. The configuration of the degradation product was obtained by means of optical rotation, 1H NMR analysis using a chiral displacement reagent, and by experimental and quantum chemical circular dichroism (CD) investigations. Based on the results obtained here and considering our previous work on the relative configuration at centers versus axis of these compounds, peroxisomicine A1 resulted to be the P,3 S,3′ S-isomer and peroxisomicine A2 the P,3 R,3′ S-isomer. Graphical Abstract