First Total Synthesis of the Bioactive Anthraquinone Kwanzoquinone C and Related Natural Products by a Diels–Alder Approach

Abstract

AbstractThe first total synthesis of the novel anticancer agent kwanzoquinone C (1), an anthraquinone glycoside which has been isolated from extracts of the roots of orange daylilies(Kaempfer) (Hemerocallis fulva) is reported. The strategy involves the preparation of the tetrasubstituted 1,3‐butadiene 6 by an electrocyclic conrotatory ring opening of the cyclobutanone rac‐11, which is obtained by a [2+2] cycloaddition.Diels–Alder reaction of 6 with the juglone derivative 5 gives the bis‐benzyl‐protected anthraquinone 4 after aromatization. Finally, glycosidation of the phenolic hydroxy group using 2,3,4,6‐tetra‐O‐acetyl‐α‐D‐glucopyranosyl trichloroacetimidate followed by the cleavage of the benzyl ethers and the solvolysis of the acetate groups yields the natural product 1. A related anthraquinone natural product 2 with antioxidative properties was obtained by using the 1,3‐butadiene 17 and the juglone derivative 16 as substrates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)