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

Abstract

The 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)

Naphthoquinones, Anthraquinones and Naphthalene Derivatives from the Bulbs ofEleutherine americana

“…The known compounds were identified as hongconin (1) (7) [3], 3-[2-(acetyloxy)propyl]-2-hydroxy-8-methoxy-1,4-naphthoquinone (9) [11], isoeleutherin (10) [1], erythrolaccin (11) [4], and 1,2-dihydroxy-8-methoxy-3-methylanthraquinone (15) [12]. Compounds 1, 3, 4, 5, 6, 7, 9, 10 and 11 had been previously isolated from E. americana.…”

Is Emodin with Anticancer Effects Completely Innocent? Two Sides of the Coin

“…Several anthraquinones added to this class of components were categorized as significant natural sources with these features. For example, glycosylated anthraquinone kwanzoquinone C isolated from the Kaempfer orange tree ( Hemerocallis fulva L.) is an interesting compound for cancer chemotherapy as it has been reported to block the growth of four different types of tumor cells (GI 50 = 3.8–7.5 µg/mL) [ 170 , 171 , 172 ]. This class of compounds has been and continues to be extensively researched due to its extensive range of biological properties.…”

1-Hydroxyanthraquinones Containing Aryl Substituents as Potent and Selective Anticancer Agents

“…(c) A mixture of 2,4-dibromo-1-hydroxyanthraquinone 3 (1 mmol) and subsequent aryl boronic acid (4,(6)(7)(8)(9)(10)(11)(12) (2.2 mmol), Pd(PPh 3 ) 4 (10 mol %), Bu 4 NBr (1 mmol) and K 2 CO 3 (4 mmol) was stirred in toluene-water mixture (100 and 20 mL) at 100 • C for 4-6 h (TLC) in an argon flow. After cooling to 25 • C, the mixture was diluted with benzene (200 mL) and washed with water.…”

“…A brief literature survey revealed that the routes for the construction of anthraquinone core are primarily based upon five categories, such as Friedel-Crafts condensations of benzene derivatives with functionalized phthalic anhydrides or phthaloyl dichlorides [8], Hauser annulations of cyanophthalides with cyclohexenones [9], Diels-Alder reactions [10,11], cross-coupling reaction and transition metal-mediated reactions [5,12] and biomimetic aldol condensations [13]. However, some annulation processes suffer from serious limitations which include the poorly efficient, and require several synthetic steps, harsh reaction conditions or using of substrates that are synthetically demanding.…”